Post on 02-Apr-2015
transcript
UTI 101 Antimicrobial agents duration and prophylaxis
April 30 2012
Jennifer J Schimmel MDBaystate Medical Center
Division of Infectious Diseases and Antimicrobial Stewardship
Objectives
bull Describe the agents used for treating bacterial urinary tract infections (UTIrsquos) and understand how to choose the most appropriate agent
bull Understand the appropriate duration of therapy and monitoring
bull Understand the options for prophylaxis of recurrent UTI
Background
bull UTI is one of the most common infections in the elderly in the community and in long-term care
bull Two problems overdiagnosis and overtreatmentbull Subsequent issuesndash C difficilendash Antibiotic resistance
bull Whatrsquos importantndash Proper diagnosisndash Appropriate antibiotic choice and duration
Defining the Problemsbull Lower UTI infection in bladder andor urethrabull Uncomplicated UTI lower UTI AND
ndash Not pregnantndash No urinary tract abnormalitiesndash No indwelling urinary device
bull Complicated UTI ndash Upper UTI (systemic symptoms extension beyond urethrabladder)ndash Functional or structural urinary tract abnormalityndash UTI in menndash Urinary catheter (CA-UTI)
ndash Older female patientsbull Many have functional or structural abnormalities
Microbiology in Nursing Homes
bull New Haven CT bull 5 Nursing Homes May 2005-2007bull 551 patients presumed UTI
Das R et al ICHE 200930(11)1116-1119
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Objectives
bull Describe the agents used for treating bacterial urinary tract infections (UTIrsquos) and understand how to choose the most appropriate agent
bull Understand the appropriate duration of therapy and monitoring
bull Understand the options for prophylaxis of recurrent UTI
Background
bull UTI is one of the most common infections in the elderly in the community and in long-term care
bull Two problems overdiagnosis and overtreatmentbull Subsequent issuesndash C difficilendash Antibiotic resistance
bull Whatrsquos importantndash Proper diagnosisndash Appropriate antibiotic choice and duration
Defining the Problemsbull Lower UTI infection in bladder andor urethrabull Uncomplicated UTI lower UTI AND
ndash Not pregnantndash No urinary tract abnormalitiesndash No indwelling urinary device
bull Complicated UTI ndash Upper UTI (systemic symptoms extension beyond urethrabladder)ndash Functional or structural urinary tract abnormalityndash UTI in menndash Urinary catheter (CA-UTI)
ndash Older female patientsbull Many have functional or structural abnormalities
Microbiology in Nursing Homes
bull New Haven CT bull 5 Nursing Homes May 2005-2007bull 551 patients presumed UTI
Das R et al ICHE 200930(11)1116-1119
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Background
bull UTI is one of the most common infections in the elderly in the community and in long-term care
bull Two problems overdiagnosis and overtreatmentbull Subsequent issuesndash C difficilendash Antibiotic resistance
bull Whatrsquos importantndash Proper diagnosisndash Appropriate antibiotic choice and duration
Defining the Problemsbull Lower UTI infection in bladder andor urethrabull Uncomplicated UTI lower UTI AND
ndash Not pregnantndash No urinary tract abnormalitiesndash No indwelling urinary device
bull Complicated UTI ndash Upper UTI (systemic symptoms extension beyond urethrabladder)ndash Functional or structural urinary tract abnormalityndash UTI in menndash Urinary catheter (CA-UTI)
ndash Older female patientsbull Many have functional or structural abnormalities
Microbiology in Nursing Homes
bull New Haven CT bull 5 Nursing Homes May 2005-2007bull 551 patients presumed UTI
Das R et al ICHE 200930(11)1116-1119
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Defining the Problemsbull Lower UTI infection in bladder andor urethrabull Uncomplicated UTI lower UTI AND
ndash Not pregnantndash No urinary tract abnormalitiesndash No indwelling urinary device
bull Complicated UTI ndash Upper UTI (systemic symptoms extension beyond urethrabladder)ndash Functional or structural urinary tract abnormalityndash UTI in menndash Urinary catheter (CA-UTI)
ndash Older female patientsbull Many have functional or structural abnormalities
Microbiology in Nursing Homes
bull New Haven CT bull 5 Nursing Homes May 2005-2007bull 551 patients presumed UTI
Das R et al ICHE 200930(11)1116-1119
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Microbiology in Nursing Homes
bull New Haven CT bull 5 Nursing Homes May 2005-2007bull 551 patients presumed UTI
Das R et al ICHE 200930(11)1116-1119
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 1
bull 75 year old woman sp recent vertebral fracture in NH for past 2 weeks no prior UTIrsquos
bull Now several days of urinary frequency urgency burning
bull No fevers or back painbull Ua with significant pyuria bull Started empirically on ciprofloxacin
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
What to use empiricallybull Take into account most likely uropathogensbull Patient Factorsndash Other medicationsinteractionsndash Allergiesndash Other past infectionsndash Other medical problems (renal insufficiency Cdiff
etc)bull Threshold for failurebull Local epidemiologybull Cost
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Antibiogram
bull Helps to determine best choices for empiric therapy
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 1 Culture DataWhat can you do now
Collect date 041512 0835 Result Status Auth (Verified)Result Date 041712 0933
SPECIMEN DESCRIPTION URINE CLEAN CATCHMIDSTREAM
SPECIAL REQUESTS NONE
CULTURE gt100000 COLML ESCHERICHIA COLI TEST PERFORMED AT BAYSTATE MEDICAL CENTER SPRINGFIELD MA 01199
REPORT STATUS FINAL 04172012
ORGANISM gt100000 COLML ESCHERICHIA COLIMETHOD MIN INHIB CONC (MCGML)AMPICILLIN RESISTANTAMPICILLINSULBACTAM INTERMEDIATEAMOXICILLINCLAVULAN SUSCEPTIBLECEFAZOLIN SUSCEPTIBLECEFEPIME SUSCEPTIBLECEFTRIAXONE SUSCEPTIBLECIPROFLOXACIN SUSCEPTIBLEERTAPENEM SUSCEPTIBLEGENTAMICIN SUSCEPTIBLELEVOFLOXACIN SUSCEPTIBLEMEROPENEM SUSCEPTIBLENITROFURANTOIN SUSCEPTIBLEPIPERACILLINTAZOBAC SUSCEPTIBLETRIMETHSULFAMETHOX SUSCEPTIBLETETRACYCLINE SUSCEPTIBLE
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Seeking the perfect antibiotichellipbull Needs to get into urinary tractndash And sometimes the prostate
bull Treat specific organismbull Narrowest spectrum possiblebull Minimize adverse effectsbull Avoid drug interactionsbull No allergybull Compliancebull Cost
bull Oral option
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 2
bull 75 year old woman with well-controlled Crohnrsquos disease on mesalamine admitted with syncopal event
bull Found to have conduction abnormalitybull Allergy to penicillin (unknown)bull Has pacemaker placed (perioperative Clindamycin)bull 2 days after procedure still has unexplained
leukocytosis with WBC 13bull no obvious source of infection no urinary symptoms
no diarrhea CXR unremarkable ua with 1 wbc
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 2
bull Urine culture pending at the time of discharge to rehab
bull What would be the next best stepA) Discharge on 5 days of Levofloxacin for possible UTIB) Follow off antibioticsC) Keep her in the hospital and repeat ua tomorrowD) Treat with Ceftriaxone 1g IV and additional antibiotics base on culture dataE) Treat with Tobramycin 5mgkg and additional antibiotics based on culture data
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
C diff-o-genicitybull High risk
ndash Carbapenemsndash 2nd ndash 4th generation
cephalosporinsndash Fluoroquinolones ndash Clindamycin
bull Medium riskndash Penicillinsndash 1st generation cephalosporinsndash Macrolidesndash Aztreonam
bull Low riskndash Aminoglycosidesndash Vancomycinndash Daptomycinndash Nitrofurantoinndash Linezolidndash Trimethoprim
sulfamethoxazolendash Tetracyclinesndash Rifampinndash Colistinndash Fosfomycin
Mullane et al Clin Infect Dis 201153440-447
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Recommendations from the Guidelines
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Uncomplicated UTI Lower Tract
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Nitrofurantoin (Macrobid Macrodantin)
bull Minimal ldquocollateralrdquo damage
bull DRUG INTERACTIONSndash Minimalndash Concomitant administration
of a magnesium trisilicate antacid may decrease the absorption of nitrofurantoin
ndash Nitrofurantoin may reduce the effect of quinolone antibiotics
ndash Fluconazole increased risk of pulmonary and hepatic toxicity
bull Avoid if creatinine clearance less than 60ndash Due to potentiation of
adverse effectsbull Common side effects
nausea headachebull Other serious adverse
effects ndash Peripheral neuropathyndash Pulmonary hypersensitivity ndash Hepatoxicityndash Decreased renal functionndash Hemolytic anemia
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Fosfomycinbull Issues
ndash Minimal resistancendash Minimal collateral damagendash High urinary levelsndash Prolonged bactericidal effectndash Minimal drug interactionsndash Not always availablendash Susceptibility data not
routinely availablendash Role for treatment of
resistant organisms such as ESBLrsquos VRE MRSA
ndash Maybe less effective than other short-course regimens
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
TrimethoprimSulfamethoxazoleTMPSMX (Bactrim)
bull DRUG INTERACTIONSndash Warfarinndash Methotrexatendash Fluconazole (incr QT)ndash TCA antipsychotics
antiarrhythmicsndash Antihyperglycemics
bull Common side effects nausea vomiting rash
bull Other serious adverse effects ndash Bone marrow suppressionndash Hepatic necrosisndash Severe rashndash Hyperkalemiandash Hypoglycemia (esp with renal
and liver disease)
bull Increased creatininehellipmay be falsely elevated
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Quinolones Ciprofloxacin and Levofloxacin
bull Highly efficacious in a 3-day regimen
bull Numerous issues with collateral damage Cdifficile and resistance
bull Save for other usesbull Black Box Warning
tendonitistendon rupture esp over age 60 steroids transplant
bull Interactions ndash calcium aluminum magnesium
iron and zinc (antacids nutritional supplements multivitamin and mineral supplements) sucralfate
ndash Warfarinndash Antihyperglycemics
bull Other issues ndash QT prolongation esp in elderlyndash Decreased seizure threshold
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Upper Tract Infection Acute Pyelonephritis
bull Not requiring hospitalization (and resistance less than 10)ndash Ciprofloxacin 500mg PO BID for 7 daysndash Ciprofloxacin 1000mg ER for 7 daysndash Levofloxacin 750mg for 5 days
ndash Bactrim DS BID for 14 days (if pathogen susceptible)
ndash Alternative initial IV antibiotic Ceftriaxone 1g IV or Aminoglycoside
ndash Alternative Oral -lactam (initial IV dose Ceftriaxone) and 10-14 days
bull Hospitalizedndash IV regimen
bull Fluoroquinolonebull Aminoglycoside +- ampicillinbull 2nd or 3rd generation cephalosporin +- aminoglycoside
bull Extended spectrum penicillin +- aminoglycosidebull Carbapenem
Gupta K et al Clinical Infectious Diseases 201152(5)e103-120
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Catheter-Associated UTI (CA-UTI)
bull Most common health care-associated infection worldwide
bull 40 of hospital-acquired infectionsbull 5-10 of LTCF residents with long-term
indwelling cathetersndash Almost all have bacteriuriandash Single organism in short-term catheterndash Multiple organisms in long-term catheterization
Hooton TM et al Clinical Infectious Diseases 201050625-663
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
CA-UTI
bull Ecoli (30) Klebsiella species Serratia species Citrobacter species Enterobacter species Pseudomonas aeruginosa coagulase-negative staphylococci Enterococcus species
bull Long-term catheters the organisms above and Proteus mirabilis Morganella morganii Providencia stuartii
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
CA-UTIbull Duration
ndash Prompt resolution of symptoms 7 days
ndash Delayed response 10-14 daysndash Not severely ill 5 day Levofloxacin may be consideredndash Women aged 65 or under with CA-UTI and no upper tract symptoms
with removal of catheter consider 3 days of therapy
bull Other issuesndash De-escalationnarrowing of therapy as soon as possiblendash If catheter in place for gt2 weeks and is still needed catheter should be
replacedbull More rapid resolution of symptomsbull Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al Clinical Infectious Diseases 201050625-663
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 3
bull 68 yo woman with poorly-controlled diabetes dysuria fever and chills
bull Prior history of UTIrsquos with resistant Klebsiellabull No allergiesbull WBC 18Kbull Cr 26bull Ua with gt182 wbc 2 rbc 1 sq epith cell
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Limited Therapeutic Options URINE CULTURE Final Organism 1 KLEBSIELLA PNEUMO SSP PNEUMO COLONY COUNT gt100000 CFUml RESULT COMMENT DRUG RESISTANT
ORGANISM Drug Resistant Organism KLEBSIELLA PNEUMO SSP PNEUMO MULTIPLE DRUG RESISTANCE TRIMETHOPRIMSULFAMETHOXAZOLE R gt=320 AMPICILLIN R gt=32 AMPICILLINSULBACTAM R gt=32 CEFAZOLIN R gt=64 CEFOXITIN R gt=64 CEFTAZIDIME R gt=64 CEFTRIAXONE R gt=64 CEFEPIME R gt=64 CIPROFLOXACIN R gt=4 GENTAMICIN R gt=16 LEVOFLOXACIN R gt=8 IMIPENEM R gt=16 NITROFURANTOIN R gt=512 TOBRAMYCIN R gt=16 AMIKACIN R gt=64 PIPERACILLINTAZOBACTAM R gt=128
bull What are the antibiotic options in this casea) Noneb) Colistinc) Gatifloxacind) Ertapeneme) Other ideas
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
New FDA Antibiotic Approvals
Boucher HW et al Clinical Infect Diseases 2009481-12
Increasing Resistant Organisms
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Answers
bull Colistinbull Tigecyclinebull Fosfomycin
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 3 Part 2
bull Patient is treated with colistin has resolution of her symptoms leukocytosis and eventually improved renal function
bull Which of the following should be doneA) Repeat ua 7 days after therapy completedB) Repeat urine culture 7 days after therapy completedC) A and BD) Repeat ua and culture are not indicated
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Test of Cure
bull Not routinely recommended
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Case 4
bull 70 year old woman with 4 Ecoli UTIrsquos in the past 6 months urologist notes a mild cystocele and atrophic vaginal mucosa on exam
bull What do you recommendedA) NothingB) Bactrim DS BID indefinitelyC) Cranberry juice 8 oz dailyD) Topical estrogenD) Cipro 500mg weekly
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Recurrent UTI Risk Factorsbull Post-menopausal
ndash estrogen deficiency ndash urogenital surgery ndash incontinence cystocele post-void residuals
bull Menndash Prostatic disease
bull Both Men and Womenndash Obstruction stones tumor
bull Complicated UTIndash MDRO obstruction stasis foley catheter stent diabetes pregnancy
renal failure transplant immunosuppression
Franco AV Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
What else other than antibioticsbull Fluids to promote a dilute urine flow bull Topical estrogenndash In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTIbull Methenaminebull Adhesion blockers (D-mannose)ndash Not evaluated in clinical trials
bull Drinking cranberry juice or cranberry tabletsndash Clinical Data Cochrane Review 2008ndash Recent studiesndash Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Mayo Clinic Proceedings 2012 Feb87(2)143-50Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily a randomized controlled trialStapleton AE Dziura J Hooton TM Cox ME Yarova-Yarovaya Y Chen S Gupta KSourceDepartment of Medicine University of Washington Seattle USAAbstractOBJECTIVE To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice dailyPATIENTS AND METHODS Premenopausal women with a history of recent UTI were enrolled from November 16 2005 through December 31 2008 at 2 centers and randomized to 1 of 3 arms 4 oz of cranberry juice daily 8 oz of cranberry juice daily or placebo juice Time to UTI (symptoms plus pyuria) was the main outcome Asymptomatic bacteriuria adherence and adverse effects were assessed at monthly visitsRESULTS A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days The cumulative rate of UTI was 029 in the cranberry juice group and 037 in the placebo group (P=82) The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 068 (95 confidence interval 033-139 P=29) The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (435) in the cranberry juice group and 8 of 10 (800) in the placebo group (P=07) The mean dose adherence was 918 and 903 in the cranberry juice group vs the placebo group Minor adverse effects were reported by 242 of those in the cranberry juice group and 125 in the placebo group (P=07)CONCLUSION Cranberry juice did not significantly reduce UTI risk compared with placebo The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger well-powered studies of women with recurrent UTI The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity
Juthani-Mehta M et al Journal of the American Geriatric Socety 201058(10)2028-2030
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
What about for CA-UTIbull Reduce indwelling catheter usebull Remove catheters the as soon as they are no
longer clinically necessary
bull Cathetersndash Care
bull Insertion with aseptic techniquesterile equipmentbull Closed drainage systems with drainage bag and tube always
below bladder levelndash Antimicrobial coating
bull May delay onset of CA-bacteriuria in short-term
Hooton TM et al Clinical Infectious Diseases 201050625-663
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
What about for CA-UTIbull Methenamine not recommended in long-term catheterization
ndash Data unconvincing that it is effectivendash May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)bull Methenamine hippurate 1 g BIDbull Methenamine mandelate 1g 4 times daily
ndash And it may help to acidify urine when using these agents (Vit C)
bull Cranberryndash 34 double-blind placebo controlled trials no effectndash Studies are poor mostly negative
bull Antimicrobial prophylaxis can reduce CA-ASB but not CA-UTIndash Not recommended because of cost potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al Clinical Infectious Diseases 201050625-663
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
In Summarybull Decide if treatment is necessarybull Appropriate antibiotic and durationndash Choice based on patient (allergiescomorbiditiesprior
history) epidemiologic factors organismndash Minimize adverse effects minimize development of
resistance avoid Cdifficilebull Narrowest spectrum possiblebull If empiric therapy is more broad than needed narrow after
culture data bull Prophylaxisndash Several options that do not affect antimicrobial resistancendash Avoid antimicrobial agents if possiblendash If such an agent is chosen would re-evaluate after several
months
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Questions
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50
Referencesbull Barbosa-Cesnik C et al Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection Results from a
Randomized Placebo-Controlled Trial Clinical Infectious Diseases 201152(1)23-30 bull Beerepoot MAJ et al Cranberries vs Antibiotics to Prevent Urinary Tract Infections Archives of Internal
Medicine 2011171(14)1270-78 bull Beveridge LA et al Optimal Management of Urinary Tract Infections in Older People Clinical
Interventions in Aging 20116173-180 bull Boucher HW et al Bad bugs no drugs no ESKAPE An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009481-12 bull Das R et al Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents ICHE 200930(11)1116-1119bull Franco AV Recurrent Urinary Tract Infections Best Pract amp Res Clin Obstet amp Gynec 200519(6)861-73bull Gupta K et al International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women A 2010 Update by the Infectious Diseases Society of America and the European Society of Microbiology and Infectious Diseases Clinical Infectious Diseases 201152(5)e103-120
bull Hooton TM Uncomplicated Urinary Tract Infection NEJM 20123661028-37bull Hooton TM et al Diagnosis Prevention and Treatment of Catheter-Associated Urinary Tract Infection in
Adults 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America Clinical Infectious Diseases 201050625-663
bull Jepson RG et al Cranberries for preventing urinary tract infections Cochrane Review 2008 bull Juthani-Mehta M et al Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents Journal of the American Geriatric Socety 201058(10)2028-2030bull Mcmurdo MET et al Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital A Double-Blind Placebo-Controlled Trial Age and Aging 200534256-261bull Mullane et al Clin Infect Dis 201153440-447bull Nicolle LE et al Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults Clinical Infectious Diseases 200540643-54 bull Stapleton AE et al Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily A Randomized Controlled Trial Mayo Clinic Proceedings 201287(2)143-50