Antimicrobial Update: A focus on prescribing in the era of resistant pathogens
Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
PresidentFitzgerald Health Education Associates, Inc.,
North Andover, MAFamily Nurse Practitioner
Greater Lawrence (MA) Family Health CenterEditorial Board Member
The Nurse Practitioner Journal, Medscape Nursing, The Prescribers Letter, American Nurse Today
Member, Pharmacy and Therapeutics CommitteeNeighborhood Health Plan, Boston, MA
Objectives
• Having completed the learning activities, the participant will be able to:– Recognize the factors that influence the
development of resistant pathogens.– Identify patient characteristics that
increase the risk of infection with a resistant pathogen.
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Objectives(continued)
• Having completed the learning activities, the participant will be able to: (cont.)– Develop a patient care plan which
takes into account the above listed data as well as the latest treatment recommendations for the treatment of select bacterial infections.
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Are the bugs winning?Is this a new problem?
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Empiric Antimicrobial Therapy
• The decision-making process where the clinician chooses the agent based on patient characteristics and site of infection.
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Questions to Ask Prior to Choosing an Antimicrobial
• What is/are the most likely pathogen(s) causing this infection?
• What is the spectrum of a given antimicrobial’s activity?
• What is the likelihood of resistant pathogen?
• What is the danger if there is treatment failure?
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What facilitates resistance?
• Time• Exposure
– Unnecessary doses– Long tx period
• Under dosing– Leaves behind
more resistant bugs
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True or false?
• In a study of antimicrobial prescribing among primary care providers, physicians in high-volume practices and those who were in practice longer were more likely to prescribe antibiotics inappropriately.
– Source- CMAJ • October 9, 2007; 177(8).
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What determines antibiotic dose?
• The pharmacological absorption and distribution of the antibiotic will influence the dose, route and frequency of administration of the antibiotic in order to achieve an effective dose at the site of infection.
– Source-http://pathmicro.med.sc.edu/mayer/antibiot.htm
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Minimum Inhibitory Concentration (MIC) Defined
• Lowest concentration of an antimicrobial that will inhibit visible growth of a microorganism after overnight incubation under standard conditions
– Source: http://jac.oxfordjournals.org/content/48/suppl_1/5.short
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Minimum Bactericidal Concentration (MBC) Defined
• Lowest concentration of antimicrobial that will prevent growth of 99.9% of an organism after subculture on to antibiotic-free media
– Source-http://jac.oxfordjournals.org/content/48/suppl_1/5.short
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Recommended Antibiotic Doses
• Usually dosed at level to 2-4 times MIC – “Overkill” amount
to allow for variations in absorption, distribution
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Updated Treatment Guidelines for ABRS in Children and Adults
Chow, A., et al., IDSA Clinical Practice Guideline for Acute
Bacterial Rhinosinusitis in Children and Adults, available at http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-
Patient_Care/PDF_Library/IDSA%20Clinical%20Practice%20Guideline%20for%20Acute%20Bacterial%20Rhinosinusitis%20
in%20Children%20and%20Adults.pdf
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Is antimicrobial neededin ABRS therapy?
• Meta-analyses of antibiotic treatment vs. placebo in ABRS– Number needed to treat (NNT)
(95% CI)• In adults=13 (9–22)• In children=5 (4–15)
– Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
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Bacterial Pathogens Associated with ABRS
• Streptococcus pneumoniae
• Gm pos diplococci• DRSP rate
nationally=25%
– Adults=38% – Children=21–33%
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– Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Bacterial Pathogens Associated with ABRS
(continued)
•Haemophilus influenzae• Gm negative rod-shaped
bacterium• ~30% beta-lactamase
production rate nationwide• Non-typable strains cause
ABRS– Adults=36% – Children=31–32%
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– Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Bacterial Pathogens Associated with ABRS
(continued)
• Moraxella catarrhalis• Gram negative with
=>90% beta-lactamase production rate
– Adults=16%– Children=8–11%
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– Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Treatment of ABRS
• Antimicrobial with activity against:–Gram positive organism S.
pneumoniae with DRSP consideration
–Gram negative organisms H. influenzae and M. catarrhalis with propensity to produce beta-lactamase
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Signs and symptoms either:a) Persistent and not improving (≥10 days);b) Severe (≥3-4 days); orc) Worsening or “double-sickening” (≥3-4 days)
Risk for Resistance
Risk for antibiotic resistance
Age <2 or >65, daycare Prior antibiotics within the
past month Prior hospitalization past 5
days Comorbidities Immunocompromised
Symptomatic management
No Yes
Initiate first-line antimicrobial therapy
Initiate second-line antimicrobial therapy
CT or MRI to investigate noninfectious causes or suppurative complications
Sinus or meatal cultures for pathogen-specific therapy
Refer to specialist
Improvement
Complete 5-7 days of antimicrobial therapy
Improvement after 3-5 days Worsening or no improvement after 3-5 days
Improvement after 3-5 days
Complete 5-7 days of antimicrobial therapy
Broaden coverage or switch to different antimicrobial class
Worsening or no improvement after 3-5 days
Complete 7-10 days of antimicrobial therapy
Improvement
Complete 7-10 days of antimicrobial therapy
Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging
Algorithm for the Management of Acute Bacterial Rhinosinusitis
Source- Clinical Infectious Diseases Advance, available at http://cid.oxfordjournals.org/
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults
Indication First-line (Daily dose)
Second-line (Daily dose)
Initial empirical therapy
Amoxicillin-clavulanate 500 mg/125 mg PO TID
Or
Amoxicillin-clavulanate 875 mg/125 mg PO BID
Amoxicillin-clavulanate 2000 mg/125 mg PO BID
Or
Doxycycline 100 mg PO BID or 200 mg PO daily
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Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults
(continued)
Risk for antibiotic resistance orfailed initial therapy
Amoxicillin-clavulanate 2000 mg/125 mg PO BID
Or Levofloxacin 500 mg PO daily
Or Moxifloxacin 400 mg PO daily
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Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults
(continued)β-lactam allergy(Containingβ-lactam ring,
penicillins,cephalosporins)
Doxycycline 100 mg PO BID Or
Doxycycline 200 mg PO dailyOr
Levofloxacin 500 mg PO dailyOr
Moxifloxacin 400 mg PO daily
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Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children
Indication First-line (Daily dose)
Second-line (Daily dose)
Initial empirical therapy
Amoxicillin-clavulanate45 mg/kg/day PO BID
Amoxicillin-clavulanate 90 mg/kg/day PO BID
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Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children
(continued)Risk for antibiotic resistance orfailed initial therapy
Amoxicillin-clavulanate 90 mg/kg/day PO BID
Or Clindamycina 30–40 mg/kg/day PO TID
plus cefixime 8 mg/kg/day PO BID or cefpodoxime 10 mg/kg/day PO BIDOr
Levofloxacin 10–20 mg/kg/day PO every 12–24 h
aResistance to clindamycin (~31%) is found frequently among Streptococcus pneumoniae serotype 19A isolates in different regions of the United States [94]. Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
24
Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children
(continued)β-lactam allergy Type I
hypersensitivity Non–type I
hypersensitivity
Levofloxacin 10–20 mg/kg/day PO every 12–24 h
Or
Clindamycina (30–40 mg/kg/day PO TID) plus cefixime (8 mg/kg/day PO BID) or cefpodoxime (10 mg/kg/day PO BID)
25
aResistance to clindamycin (~31%) is found frequently among Streptococcus pneumoniae serotype 19A isolates in different regions of the United States [94]. Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults
How Would you PrescribeCephalosporins to Patients with
Penicillin Allergies?Article by Margaret A. Fitzgerald,
DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
Available at http://fhea.com/main/content/Newsletter/fheanews_vol
ume12_issue8.pdf
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Urinary Tract Infection
• Second most common infectious complaint in outpatient primary care clinics
• Most common outpatient complaint caused by bacteria
– Source- Car J. Urinary Tract Infections in Women: Diagnosis and management in primary care. BMJ. 2006;332:94-97
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Which commonly reported symptom is most sensitive for UTI?
• Frequency• Burning• Straining• Urgency• Pain with voiding
– Source- Bowen, A., Hellstrom, Urinary Tract Infections: A Primer for Clinicians, available at http://www.medscape.com/viewprogram/7049
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Evidence-based UTI Prevention:True or false?
In order to minimize risk of urinary tract infection, women should be
advised about:
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True or false?Evidence-based Methods to AvoidUrinary Tract Infection in Women
• Postcoital voiding• Timed or frequent voiding• Wipe front to back• Avoid hot tub use• Do not wear pantyhose
– Source- Car J. Urinary Tract Infections in Women: Diagnosis and management in primary care. BMJ. 2006;332:94-97.
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Acute Uncomplicated Cystitis: Risk Factors for Women
• Heterosexual intercourse– UTI more frequent in 15-35 year-old
women– Intercourse often precedes UTI onset – Frequency of intercourse often related
to UTI incidence– Source- Fitzgerald, M., Lie, D., Urinary Tract Infection:
Providing the Best Care, available at www.medscape.com/viewprogram/1920
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Acute Uncomplicated Cystitis: Risk Factors for Women
(continued)• Low lactobacilli colonization
– Normal periurethral flora component• Produces hydrogen peroxide, lactic acid
– Provides periurethral area, vagina w/ pH that inhibits bacterial growth, blocks potential sites of attachment toxic to uropathogens
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– Source- Fitzgerald, M., Lie, D., Urinary Tract Infection: Providing the Best Care, available at www.medscape.com/viewprogram/1920
Acute Uncomplicated Cystitis: Risk Factors for Women
(continued)
• Low lactobacilli colonization (cont.)– Postmenopausal women– Recent antimicrobial use– Spermicides containing antibacterial
detergent benzethonium chloride– Likely tampon use
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– Source- Fitzgerald, M., Lie, D., Urinary Tract Infection: Providing the Best Care, available at www.medscape.com/viewprogram/1920
UTI TherapiesSource- Gilbert, D., Moellering, R., Eliopoulos, G.,
Chambers, H., Saag, M. (2013) The Sanford Guide to Antimicrobial Therapy (43th ed.). Sperryville, VA:
Antimicrobial Therapy, Inc.
Fitzgerald Health Education Associates, Inc. 34
Fitzgerald Health Education Associates, Inc. 35
Type of infection
Usual pathogens
Regimens
Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women
E. coli (Gm neg, most common pathogen),S. saprophyticus (Gm pos), Enterococci (Gm pos)
PrimaryIf local E. coli resistance to TMP/SMX<20% and no allergy, then TMP/SMX-DS BID x 3 daysIf local E. coli resistance to TMP/ SMX>20% or sulfa allergy, nitrofurantoin 100 mg BID X 5 d or fosfomycin X 1 dose, all plus phenazopyridine (Pyridium®)
Type of infection
Usual pathogens
Regimens
Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women(cont.)
E. coli (Gm neg, most common pathogen),S. saprophyticus (Gm pos), Enterococci (Gm pos)
AlternativeIf local E. coli resistance to TMP/ SMX>20% or sulfa allergy, ciprofloxacin 250 mg BID, ciprofloxacin ER 500 mg daily, levofloxacin 250 mg daily, or moxifloxacin 400 mg daily, all for 3 days, all plus phenazopyridine (Pyridium®)
Gemifloxacin not labeled for use in UTI, likely effective.
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Type of infection
Usual pathogens
Regimens
Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women(cont.)
E. coli (Gm neg, most common pathogen),S. saprophyticus (Gm pos), Enterococci (Gm pos)
Alternative (cont,)Amoxicillin-clavulanate 875/125 mg BID x 5-7 days or an oral cephalosporin (e.g., cephalexin 500 mg QID x 5-7 days or cefpodoxime proxetil 100 mg BID x 3 days)
Beta-lactams generally less efficacious than fluoroquinolones or TMP-SMX and should be reserved for cases where other agents cannot be used.
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Per Sanford Guide
• Fosfomycin– 3 G taken as a 1 time dose
• Spectrum of antimicrobial activity– Less effective vs. E. coli when
compared to multiple doses of TMP-SMX
– Active again E. faecalis, poor activity against other coliforms
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Fosfomycin (Monurol®)
• Indications– Treatment of uncomplicated UTIs in
women due to susceptible strains of Escherichia coli and Enterococcus faecalis
– Not indicated for the treatment of pyelonephritis or perinephric abscess
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• Pregnancy risk category– B based largely on lab animal studies
• Cost– 1 packet=1 dose=~$45 on
drugstore.com
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Fosfomycin (Monurol®) (continued)
Fosfomycin (Monurol®) per PI
• Do not use more than one single dose of Monurol® to treat a single episode of acute cystitis. Repeated daily doses of Monurol® did not improve the clinical success or microbiological eradication rates compared to single dose therapy, but did increase the incidence of adverse events.
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Per up to Date
• Fosfomycin- A single-dose 3 gram sachet is an acceptable agent for women with mild to moderate infections who cannot take TMP-SMX or nitrofurantoin.
– Source- http://www.uptodate.com/contents/acute-uncomplicated-cystitis-and-pyelonephritis-in-women?detectedLanguage=en&source=search_result&search=Fosfomycin&selectedTitle=1%7E9&provider=noProvider
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Extended Spectrum Beta Lactamase-producing Strains
• AKA ESBL-producing strains• Most often K. pneumoniae, E. coli,
Acinetobacter– Usually effective antimicrobials
include nitrofurantoin, fosfomycin, or amoxicillin-clavulanate plus cefdinir
– Source- 2013 Sanford Guide
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Length of Therapy in Select Populations
• For patients with DM, symptoms greater than 7 days, recently used antimicrobials, =>age 65 yr, or male
44
– Source- Gupta, K., Stamm, W. Best Dx/Best Tx, Urinary Tract Infection, available http://www.acpmedicine.com
• 7-day regimen – Oral TMP-SMX – Fluoroquinolone – Cefixime 400 mg daily– Cefpodoxime 100-200 mg daily– Other cephalosporin as appropriate
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Length of Therapy in Select Populations
(continued)
– Source- Gupta, K., Stamm, W. Best Dx/Best Tx, Urinary Tract Infection, available http://www.acpmedicine.com
Skin Abscess, Boils, FurunclesSource- Gilbert, D., Moellering, R., Eliopoulos, G.,
Chambers, H., Saag, M. (2013) The Sanford Guide to Antimicrobial Therapy (43th ed.). Sperryville, VA:
Antimicrobial Therapy, Inc.
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Purulent Skin Lesions: Boils, Furuncles, Carbuncles Abscesses
● Incision and drainage=Mainstay of therapy
● Community-associated MRSA of concern for effective management
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• Staphylococcus aureus• Gram positive cocci that
appear in grape-like clusters
– Methicillin sensitive (MSSA)• Implies beta-lactamase
producing organism
– Methicillin resistant (MRSA)• Implies altered antibiotic-
binding sites within organism, could also produce beta-lactamase
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Etiologies
Primary Regimens
• Patient is afebrile and abscess <5 cm in diameter– Incision and drainage only is usually
effective.– Hot packs are helpful.– No need for antimicrobial therapy
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• Patient afebrile abscess ≥5 cm in diameter– Incision and drainage – Likely adequate alone, as the 5 cm
cut-off not rigorously established as an indication for adjunct antimicrobial therapy
Primary Regimens (continued)
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• Patient afebrile and abscess ≥5 cm in diameter (cont.)– TMP-SMX-160/800 (1 DS tab) PO BID x 5–10
days • Or
– Clindamycin 300-450 mg PO TID x 5–10 days • Or
– Doxycycline 100 mg PO q12h • Or
– Minocycline 100 mg PO q12h x 5–10 days
Primary Regimens (continued)
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• Patient is febrile and abscess is large and/or multiple abscesses– Outpatients
• Incision and drainage: Culture abscess and consider obtaining blood cultures
• Empirical antibiotic therapy
Primary Regimens (continued)
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Primary Regimens (continued)
• Patient is febrile and abscess is large and/or multiple abscesses (cont.)– Outpatients (cont.)
• Empirical antibiotic therapy…(cont.)–Clindamycin 300-450 mg PO TID x 7-10
days »Or
–TMP-SMX 160/800 mg (i.e., 1 double strength tab) PO BID x 7-10 days »Or
–Doxycycline 100 mg PO BID x 7-10 days53 Fitzgerald Health Education Associates, Inc. Fitzgerald Health Education Associates, Inc. 54
• Patient is febrile and abscess is large and/or multiple abscesses (cont.)– Outpatients (cont.)
• Empirical antibiotic therapy…(cont.)–If no response after 2-3 days, look for
complications and consider vancomycin 1 gm IV q12h
Primary Regimens (continued)
• For MRSA infections – Oral agents
• Linezolid 600 mg PO q12h
– Parenteral agents• Daptomycin 4 mg/kg IV q24h (give higher
dose if bacteremic patient)• Linezolid 600 mg IV q12h
Alternative Regimens (continued)
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• One double-strength tab of TMP-SMX twice daily as effective as two double-strength tabs twice daily
– Source- Antimicrob Agents Chemother 55:5430, 2011.
– Lower dosage range of TMP-SMX (1 DS instead of 2 DS) and clindamycin (150-300 mg instead of 450 mg) found to be associated with treatment failure in obese patients (BMI>40)
– Source- J Infect 65:128, 2012.
Alternative Regimens (continued)
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Alternative Regimens
• For documented MSSA infection– Oral agents
• Dicloxacillin 500 mg PO QID – Or
• Flucloxacillin 250-500 mg PO QID – Or
• Cephalexin 500 mg PO QID
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Alternative Regimens (continued)
• For documented MSSA infection, a beta-lactam preferred agent (cont.)– Parenteral agents
• Nafcillin or oxacillin 1 gm IV q4h – Or
• Flucloxacillin 1 gm IV q6h – Or
• Cefazolin 1 gm IV q8h
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To pack or not to pack?
What is the evidence?http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231432/
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Recurrent Furunculosis
• There is no "gold standard" regimen.
• Optimal regimen and duration of treatment are uncertain.
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Recurrent Furunculosis: Documenting Colonization
(continued)
• Need to culture multiple sites–Nose, throat and inguinal area
skin.–Nares only culture missed 48% of
colonized individuals –Source- Clin Infect Dis 54:1523, 2012
• Does not apply to care of IDU Fitzgerald Health Education Associates, Inc. 61
Primary Regimens: Recurrent Furunculosis
• (Doxycycline 100 mg PO BID + rifampin 300 mg PO BID x 7 days) + (mupirocin ointment in anterior nares and under fingernails 2x/day x 7 days) + (chlorhexidine 4% {Hibiclens® OTC} shower daily x 7 days)
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• Resistance of S. aureus to rifampin can develop quickly. In theory, to lower the risk can give the doxycycline 100 mg PO BID for 5 days to lower the inoculum of organisms and then continue the doxycycline and add rifampin 300 mg PO BID for another 5 days. Total of 10 days of doxycycline and 5 days of rifampin.
Primary Regimens (continued)
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Alternative Regimens
• TMP-SMX double strength tab PO BID + rifampin 300 mg PO BID x 7 days + mupirocin ointment (as above)+ chlorhexidine shower (as above)
– Source- Infect Control Hosp Epidemiol 32:872, 2011
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Alternative Regimens (continued)
• Bleach baths (tub of warm water with 1/4 cup of 6% sodium hypochlorite (Clorox®, household bleach) for 15 minutes, is as effective as use of chlorhexidine shower body washes.
– Source- Infect Control Hosp Epidemiol 32:872, 2011
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Comments
• If patient is a known carrier of MSSA, can use dicloxacillin 500 mg PO QID instead of doxycycline or TMP-SMX.
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And last but not least on antibiotic sparing behavior…
Acute bronchitis
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True or false?
• In otherwise healthy patients, purulent sputum usually indicates the presence of sloughed tracheo-bronchial epithelium and inflammatory cells, not bacterial burden.
– Source- Gonzales R, Sande MA. Uncomplicated acute bronchitis. Ann Intern Med 2000; 133:981-991.
68 Fitzgerald Health Education Associates, Inc.
True or false?
• In a study involving 2781 healthy adults, the median duration of cough from acute bronchitis due to all causes was 18 days.
– Source- Ward JI., Cherry JD., Chang S-J., et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005; 353:1555-1563.
69 Fitzgerald Health Education Associates, Inc.
Table 10-8: Acute Bronchitis: Likely Causative Pathogens
Organism % of total CommentRespiratory tract viruses
Consider using anticholinergic bronchodilator such as ipratropium bromide (Atrovent®) or inhaled beta2-agonist such as albuterol or short course of oral corticosteroid with protracted, problematic cough.
Fitzgerald Health Education Associates, Inc. 70
90
Table 10-8: Acute Bronchitis: Likely Causative Pathogens
(continued) Organism % of total Comment
Bacterial pathogens such as M. pneumoniae, C. pneumoniae, B. pertussis
Consider use of macrolide or tetracycline form when antimicrobial therapy indicated.
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10
Conclusion
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End of Presentation!Thank you for your time and attention.
Fitzgerald Health Education Associates, Inc. 73
Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
www.fhea.com [email protected]
Fitzgerald Health Education Associates, Inc. 74
All websites listed active at the time of publication.
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