Sepsis Urinaria CCC 7-13

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Urinary Tract Infection

Lindsay E. Nicolle, MD

INTRODUCTION

Urinary tract infection presents as the clinical syndromes of acute, uncomplicated, uri-

nary infection, including acute nonobstructive pyelonephritis; complicated urinary

tract infection; asymptomatic bacteriuria; and, in men, bacterial prostatitis. Severe

or life-threatening infection usually occurs with complicated urinary infection. Compli-

cated urinary infection occurs in men and women with functional or structural abnor-

malities of the urinary tract. Obstruction or mucosal trauma are the most common

precipitating events for urosepsis. Although 20% to 30% of women with acute nonob-

structive pyelonephritis or men with acute bacterial prostatitis have bacteremia, these

syndromes seldom progress to severe sepsis or shock.

EPIDEMIOLOGYFrequency

The urinary tract is a common source of infection for patients who present with severe

sepsis or septic shock. In a US tertiary care medical facility, the urinary tract was the

source for 40% of patients who presented to the emergency department with septic

shock and 25% of inpatients who developed septic shock.1 In two cohorts of adult

Department of Internal Medicine, Health Sciences Centre, University of Manitoba, RoomGG443, 820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, CanadaE-mail address: [email protected]

KEYWORDS

Urosepsis Pyelonephritis Complicated urinary infection Bacteremia

KEY POINTS

The urinary tract is one of the most common sources for life-threatening infections.

Severe infections usually occur in individuals with complicated urinary tract infection,

including after urologic procedures in which appropriate perioperative prophylaxis is

not given.

A broad range of organisms may be isolated, depending on whether it is community-

acquired or health careacquired and prior exposure of the patient to antimicrobials.

Effective antimicrobial therapy requires an agent that is excreted by the kidneys.

The prognosis is generally better for urosepsis than for other common infection sources of

septic shock.

Crit Care Clin 29 (2013) 699715http://dx.doi.org/10.1016/j.ccc.2013.03.014 criticalcare.theclinics.com0749-0704/13/$ see front matter 2013 Elsevier Inc. All rights reserved.
mailto:[email protected]://dx.doi.org/10.1016/j.ccc.2013.03.014http://criticalcare.theclinics.com/http://criticalcare.theclinics.com/http://dx.doi.org/10.1016/j.ccc.2013.03.014mailto:[email protected]


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patients with septic shock admitted to critical care units from 1996 to 2007, in 28 fa-

cilities in Canada, the United States, and Saudi Arabia, the urinary tract was the source

of sepsis for 14.7% and 18.3%.2 The urinary tract was the source for 30.2% of Austra-

lian and NewZealand patients presenting to emergency departments with sepsis and

septic shock.3 Some series report a lower proportion of patients with a urinary source.

In 12 intensive care units in France, 8.4% of patients with septic shock had a urinary

source4 and a 1-year prospective study of patients admittedwith sepsis to intensive

care units in Iceland reported a urinary source for only 8%.5

The proportion of subjects presenting with different types of urinary infection who

develop severe sepsis or shock are summarized in Table 1. Bacteremic complicated

urinary infection and urologic procedures without appropriate perioperative antimicro-

bial prophylaxis carry a high risk of life threatening infection. In women with acute

nonobstructive pyelonephritis, on the other hand, progression to septic shock is

exceptional and, should it occur, suggests an underlying complicating factor. Urinary

tract infection is also acquired by patients in the critical care unit, attributable to the

high prevalence of indwelling catheter use in this setting. However, few of these infec-

tions are severe. Laupland and colleagues16 reported an incidence density of urinary

infection acquired in the critical care unit of 9.6/1000 ICU days during a 3-year period

in a regional critical care system, but the bacteremia or fungemia rate with infection

was only 0.1/1000 ICU days.

Risk Factors

Several risk factors are associated with the most severe presentations of urinary tract

infection (Table 2). In a Korean study of bacteremic urinary infection, urinary tract

Table 1

Proportion of subjects developing severe sepsis or septic shock

Country, Reference Population Severe Sepsis or Shock

UK6 Percutaneous nephrolithotomy Antibiotic: 13.5%No antibiotic: 33%

India7 Percutaneous nephrolithotomy Antibiotic: 19%No antibiotic: 49%

Taiwan8

Community-onset bacteremic UTI ESBL: 41.7%Not ESBL: 4.4%

Israel9 Proteus mirabilisUTI 28.3%

Taiwan10 P mirabilisUTI Bacteremia: 31.3%No bacteremia: 22.6%

Taiwan11 ESBL urosepsis Community-acquired: 0Health careassociated: 19.5%Hospital-acquired: 14.4%

Korea12 Complicated pyelonephritis,bacteremia

Community-acquired: 19.2%Health careacquired: 46%

Israel13

Women, complicated pyelonephritis 13.3%US14 Women admitted for parenteral

therapy, acute uncomplicatedpyelonephritis

0

Korea15 UTI bacteremia, nosocomialacquisition

25%

Abbreviations: ESBL, extended spectrum beta-lactamase; UTI, urinary tract infection.

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obstruction (odds ratio [OR] 4.39; 95% CI 1.7810.82), health careassociated infec-

tion (OR 3.49; 1.597.69), and liver cirrhosis (OR 4.6; 1.4015.22) were independent

predictors of septic shock.12A case-control study of patients withEscherichia coliuri-

nary infection reported clinical presentations of hesitancy and/or retention (OR 7.8;

1.637), a history of urogenital procedure (OR 5.4; 214.7), and presence of the kps

MT virulence gene in theE colistrain isolated were independent predictors of bacter-

emia.17 Other potential risk factors for life-threatening urinary infection include poorly

controlled diabetes, neutropenia, and elderly patients.

Microbiology

A wide spectrum of organisms are isolated from patients with complicated urinary

infection (Table 3) and may be the causative organism for patients with septic shock.

The relative proportions of different species varies with patient characteristics and

the likelihood of health careacquisition. E coli is the most common organism iso-

lated for community-acquired infections but is less common in health careacquired

infections. E coli isolated from women with acute nonobstructive pyelonephritis are

characterized by specific virulence features, including the Pap pilus. However, for

patients with complicated urinary tract infection expression ofE coli, virulence fac-tors does not predict more severe presentations.23,24 Enterococcus spp and

Candidaspp are more frequent in patients with indwelling devices.1921 OtherEnter-

obacteriaceae, gram-positive organisms, and nonfermenters such Pseudomonas

aeruginosa, Acinetobacter spp, and Stenotrophomonas spp, are also occasionally

isolated.

A retrospective review of patients at one US hospital reported that 14.2% of patients

with septic shock and blood cultures positive forCandidaspp had a urinary source for

infection.25 Risk factors for isolation of yeast species include presence of diabetes,

chronic indwelling catheters, and broad-spectrum antimicrobial therapy.26 Organisms

isolated from complicated urinary tract infection tend to be more resistant to antimi-crobials, particularly for patients with health careacquired infections. Extended spec-

trum beta lactamase (ESBL) and carbapenemase-producing E coli and Klebsiella

pneumoniaeare increasingly isolated from community-acquired and health careac-

quired infections. The urinary tract was reported to be the source for 72% of patients

with ESBL-producingE coliandK pneumoniaebacteremia presenting to a Taiwanese

emergency department.27

Table 2

Risk factors for more severe presentations of urinary infection

Variable Reference

Urinary obstruction 12,17

Hydronephrosis 6

Mucosal trauma in patients with bacteriuria, including urologic surgeryand indwelling catheters

6,17

Prolonged urologic surgery 6

Infection with selected organisms, including resistance 8,17

Health careacquired infection 11,12

Liver cirrhosis 12

Female gender 6

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Table 3

Organisms isolated from selected patients with severe presentations of complicated urinary tract infection

Reference 18 19 20 21

Population Bacteremia, HCA, Quebec Bacteremia, CA-UTI,United States

Elderly, Bacteremia, Korea Elde

E coli 47% 12.8% 81% 46.1

Klebsiella pneumoniae 12% 5.6% 7.0% 13.5

P mirabilis 1.6% 7.8%

Enterobacteriaceae 10% 6.8% 3.5% 3.6

Pseudomonasspp 6% 8.1% 15.5

Acinetobacterspp 1.2 1.0

Enterococcusspp 8% 28.4% 3.6

Staphylococcus aureus 8% 8.8% 3.5% 8.3

Coagulase-negativestaphylococcus

4% 5.9%

Streptococcusspp 0.9% 0.5

Other gram positive 4.7%

Other 3%

Candidaspp 2% 19.7%

Abbreviations:CA-UTI, catheter-acquired urinary tract infection; HCA, health careacquired.


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DIAGNOSIS

Definitions

The International Sepsis Forum Consensus Conference Definitions of Infection in the

Intensive Care Unit for urosepsis are summarized in Box 1 for noncatheterized pa-

tients andBox 2

for catheterized patients.

28

These definitions were developed to stan-dardize the diagnostic criteria for patient enrollment into clinical trials. They have not

yet, however, been validated for use, and the utility in clinical care is not yet known.

History

Relevant history suggesting a urinary source of infection includes:

Recent urologic intervention: sepsis following a urologic procedure in patients

with preexisting bacteriuria usually presents within 24 hours of the procedure

Indwelling urethral catheter or presence of other devices such as ureteric stents

or nephrostomy tubes: recent catheter trauma or catheter obstruction increases

the likelihood of a urinary source for fever

Symptoms consistent with renal colic: severe flank pain radiating to the

groin suggests ureteric calculus and obstruction rather than nonobstructive

pyelonephritis

Presence of gross hematuria

Lower tract irritative symptoms (dysuria, hesitancy, urgency)

Recent antimicrobial treatment of urinary tract infection.

Physical Examination

Costovertebral angle tenderness, hematuria, or presence of an indwelling device arelocalizing findings suggesting a genitourinary site of infection. However, patients with

urinary infection may have no localizing signs, or may not be able to communicate

symptoms. The most common presentation of urinary infection in the patient with

an indwelling urethral catheter is fever alone. In the absence of localizing genitourinary

findings, the diagnosis of urinary infection is a diagnosis of exclusion (ie, no other sites

for infection are apparent). The nonspecific presentation of some patients means

Box 1

Criteria for definition of urosepsis in noncatheterized patients

Upper urinary tract infection (kidney, ureter, or tissue surrounding the retroperitoneal or peri-nephric space)

One of:

Organism isolated from culture of fluid (other than urine) or tissue from the affected site

An abscess or other evidence of infection seen on direct examination during surgery or byhistopathology examination

Or two of:

Fever (>38C)

Urgency

Localized pain or tenderness at involved site

Any one of: microscopic examination (urinalysis or Gram stain) with pyuria or 105 colonyforming unit (cfu)/ml; purulent drainage from the affected site; pyuria; hematuria;organism isolated from urine culture; positive Gram stain; radiographic evidence of infection(eg, ultrasound, computed tomography, magnetic resonance imaging, radiolabeled scan).



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urinary tract infection is frequently overdiagnosed as a source for fever, including

among critical care unit patients.29

Urine Culture

A definitive diagnosis of urinary tract infection usually requires a positive urine culture.

Exceptions to this occur when there is an abscess of the renal cortex or perinephric

space that does not communicate with the renal tubules, an infected renal cyst, or

when the infection is proximal to a complete obstruction within the urinary tract. Sys-

temic antimicrobial therapy will usually sterilize the urine within minutes. Thus, a urine

Box 2

Criteria for definition of urosepsis in the catheterized patient

1. Lower urinary tract infection

a. Presence of suggestive signs and symptoms, including fever (>38C), urgency, frequency,

dysuria, pyuria, hematuria, positive Gram stain, pus, suggestive imaging

and

b. Positive dipstick for leukocyte esterase and/or nitrate or pyuria (10 white blood cells/mLor 3 white blood cells or high-power field of unspun urine) ororganisms seen on Gramstain of unspun urineorfrank pus expressed around the urinary catheteror>103 CFU/mLorif the patient can report symptoms, modified Centers for Disease Control andPrevention (CDC) criteria must be met

2. Upper urinary tract infection (kidney, ureter, bladder, urethra, or tissue surrounding theretroperitoneal or perinephric space)

a. One of the following criteria: Organism isolated from culture of fluid (other than urine)or tissue from the affected site, an abscess or other evidence of infection seen on directexamination during surgery, or by histopathologic examination

b. Ortwo of the following: Fever (>38C), urgency, localized pain or tenderness at involvedsite,andany of: purulent drainage from the affected site, pyuria, hematuria, organismisolated from culture, positive Gram stain, radiographic evidence of infection (eg,ultrasound, CT, MRI, radiolabeled scan)

3. Modified CDC criteria

a. One of: fever (>38C), urgency, frequency, dysuria or suprapubic tenderness, and a urineculture 105 CFU/mL, with no more than two species of organism

or

b. Two of: fever (>38C), urgency, frequency, dysuria, or suprapubic tenderness, and anyone of:

i. Positive dipstick for leukocyte esterase and/or nitrate

ii. Pyuria (10 white blood cells/mL or 3 white blood cells or high-power field ofunspun urine)

iii. Organisms seen on Gram stain of unspun urine

iv. Two urine cultures with repeated isolation of the same uropathogen with102 CFU/mL, in a nonvoided specimen

v. Two urine cultures with 105 CFU/mL of single uropathogens in a patient beingtreated with appropriate antimicrobial therapy

From Calandra T, Cohen J, International Sepsis Forum Definition of Infection in the ICUConsensus Conference. The international sepsis forum consensus conference on definitionsof infection in the intensive care unit. Crit Care Med 2005;33:153848; with permission.

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specimen for culture should be collected before initiation of antimicrobial therapy. A

single organism is usually isolated; however, polymicrobial bacteriuria is common in

subjects with chronic indwelling catheters, elderly functionally impaired patients,

and some patients with complex genitourinary abnormalities.

The urine specimen must be collected using a method that minimizes contamination.

The specimen may be collected when an indwelling catheter is inserted for output moni-

toring or other indications. When an indwelling catheter is in situ, the urine specimen

should be collected from the catheter port or through catheter puncture using a sterile

needle and syringe. A chronic indwelling catheter in situ for 2 weeks or longer will have

substantial biofilm formation along the catheter surface. Urine collected through the

tubing of these catheters is contaminated by organisms growing in the biofilm that

may not be present in the bladder. The catheter should be replaced by a sterile catheter

and a urine specimen collected immediately through the new catheter to obtain a spec-

imen of bladder urine.30 When there is obstruction of the urinary tract, an abscess, or

infected renal cyst, the specimen for culture should be collected by percutaneous aspi-

ration, if possible. The method of specimen collection should be noted on the specimen

requisition, so the laboratory has relevant information for processing.

Correct interpretation of the quantitative urine culture is essential for appropriate

management of urinary infection. Urine is an excellent culture media for most aerobic

organisms. When small numbers of organisms are inoculated into the bladder, quan-

titative counts of105 colony-forming units (CFU)/mL are achieved within a few hours

of incubation. Patients with indwelling urethral catheters have a pool of urine retained

in the bladder because of the catheter bulb. Thus, 105 CFU/mL of the infecting or-

ganisms should be isolated from the urine for most patients with urinary infection.

Some exceptions to this include: When patients are undergoing diuresis, organisms may not remain in the bladder

long enough to achieve the higher quantitative counts.

Lower quantitative counts are occasionally isolated from urine specimens of pa-

tients receiving antimicrobial therapy at the time of specimen collection.

For Candida spp, 104 CFU/mL is considered the appropriate quantitative

count.28

A quantitative count of102 CFU/mL of a uropathogen is appropriate for diag-

nosis of bacteriuria when a specimen is collected by in and out catheter or imme-

diately following the insertion of an initial indwelling catheter.

Lower quantitative counts isolated from patients with chronic indwelling cathe-

ters are often attributable to catheter biofilm contamination rather than bladder

bacteriuria.

Asymptomatic bacteriuria is common in many populations with complicated urinary

infection, including virtually all patients with chronic indwelling catheters. In the

absence of localizing genitourinary signs and symptoms, a positive blood culture or

diagnostic imaging to support a urinary source for infection, a positive urine culture,

by itself, does not confirm urinary tract infection. Golob and colleagues29 described

60 specimens with bacteriuria in 407 urine cultures obtained from subjects in 42 crit-

ical care units. Bacteriuria was not associated with fever, leukocytosis, or the combi-nation of fever and leukocytosis in these patients. Symptomatic urinary infection is

overdiagnosed and overtreated in patients with asymptomatic bacteriuria.

Blood Cultures

A positive blood culture confirms the identification and susceptibilities of the infecting

organism and supports a diagnosis of urinary infection when similar organisms are



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isolated from the blood and urine. Rarely, the same species is isolated from urine and

blood but with different susceptibilities. If there are multiple organisms isolated from

the urine culture, a positive blood culture assists in identifying the clinically important

strains for selection of antimicrobial therapy. Documentation of a positive blood cul-

ture may also be relevant for patients who subsequently develop metastatic infection,

which may present weeks or months after the initial infection.

Urinalysis

Pyuria accompanies symptomatic urinary infection but is a nonspecific finding. It is

present for most patients with asymptomatic bacteriuria and is common with any in-

flammatory condition of the genitourinary tract including following urologic surgery,

interstitial nephritis, or presence of indwelling urinary devices. The absence of pyuria

may be useful to exclude urinary infection, but the presence of pyuria will not confirm

bacteriuria or differentiate symptomatic urinary tract infection from asymptomatic

bacteriuria.

Inflammatory Markers

The procalcitonin level predicts bacteremia in patients with febrile urinary tract infec-

tion.31 Further evaluation of the utility of initial or serial procalcitonin levels is necessary

to determine the utility of this parameter in predicting outcomes or assisting in the

management of life-threatening urinary infections.

Diagnostic Imaging

When a patient presents with a suspected urinary source for severe sepsis or septic

shock, diagnostic imaging should be performed urgently to identify and characterizeabnormalities that may require source control, unless the contributing factor is already

apparent. Imaging studies may identify severe unilateral or bilateral pyelonephritis,

intrarenal or perinephric abscesses, emphysematous pyelonephritis, and obstruction

at any level. An infused CT scan is the optimal diagnostic imaging modality.32 Renal

and pelvic ultrasound is not as sensitive as CT, but will identify many abnormalities

and be more accessible in some settings. MRI is not as reliable for identifying stones

or gas in tissues, and is not recommended for initial imaging for identification of a po-

tential source for urosepsis.

ANTIMICROBIAL MANAGEMENTPharmacokinetic Considerations

Optimal therapy of urinary tract infection requires treatment with antimicrobial agents

that are excreted by the kidneys and achieve high levels in renal tissue and urine.33

Treatment with antimicrobials without renal excretion may be effective to resolve

bacteremia and improve symptoms, but often will not eradicate organisms from the

urinary tract. Relapse of the infection can occur once the antimicrobials are discontin-

ued. There is decreased blood flow to the affected kidney in patients who have severe

obstruction to urine flow, a unilateral nonfunctioning kidney, or renal failure. The

impaired excretion of antimicrobials by the affected kidney means adequate tissue

and urine antimicrobial levels may not be achieved. Patients with renal impairmentmay require more prolonged antimicrobial therapy and, in some cases, it may not

be possible to achieve microbiologic cure.

Guidelines

The European Association of Urology has published guidelines for antimicrobial ther-

apy for management of urosepsis.34 The recommended agents include an extended

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spectrum cephalosporin (cefotaxime, ceftriaxone, ceftazidime), fluoroquinolone with

mainly renal excretion (ciprofloxacin, ofloxacin, levofloxacin), anti-pseudomonas active

acylaminopenicillin/beta lactamase inhibitor (piperacillin/tazobactam), or a carbape-

nem (imipenem, meropenem, ertapenem, doripenem)all with or without an aminogly-

coside. The recommended duration for therapy is 3 to 5 days after defervescence or

control of the complicating factor.

Clinical Trials

The clinical trial evidence to support selection of a specific antimicrobial regimen for

empiric treatment of life-threatening urinary infection is limited. In a recent evidence-

based review, 79 articles relevant to empiric antimicrobial therapy for patients with se-

vere sepsis and septic shock were identified, but none of these specifically addressed

urinary tract infection.35 A few comparative clinical trials have enrolled patients with

complicated urinary infection but have excluded subjects with life-threatening infec-

tion. In trials of parenteral antimicrobial therapy for complicated urinary infection, levo-floxacin was as effective as doripenem,36 ertapenem was similar to ceftriaxone,37

cefepime to ceftazidime,38 and aztreonam to cefotaxime.39

Empiric Antimicrobial Therapy

Patients with life-threatening urinary tract infection require prompt institution of

empiric broad spectrum antimicrobial therapy selected to provide coverage for poten-

tial pathogens. The observation that earlier initiation of antimicrobial therapy improves

survival with septic shock is consistent for patients with a urinary source.2,4 Many an-

timicrobials are effective (Table 4). During selection of the specific regimen, consider-

ation should be paid to the likely infecting organism and susceptibilities, current orrecent antimicrobial therapy received by the patient, local antimicrobial resistance

prevalence, and patient renal function and tolerance. Patients with health careac-

quired infections or recent antimicrobial therapy for any indication have a higher likeli-

hood of infection with a resistant organism.

Aminoglycosides are concentrated within renal tubular cells and are very effective

for the treatment of pyelonephritis. However, this class of antimicrobials has limited

perfusion into the kidney when there is renal impairment and are less effective for treat-

ment of these patients. In addition, the side effects of eighth nerve toxicity and renal

impairment are of concern. Empiric therapy with an aminoglycoside is appropriate if

resistant organisms or patient intolerance limit the use of other effective agents. Theappropriateness of continuation of aminoglycoside therapy should be reassessed

once urine culture results are known. If the aminoglycoside must be continued, moni-

toring of antimicrobial levels and renal function are necessary.

Ciprofloxacin and levofloxacin are the recommended fluoroquinolones; moxifloxa-

cin has limited urine excretion and is not indicated for the treatment of urinary tract

infection. Cefotaxime is preferred to ceftriaxone for patients with renal failure. Ceftri-

axone has increased biliary excretion when there is renal failure, so effective antimi-

crobial levels may not be achieved in the kidney. There is no evidence that dual

therapy improves outcomes with urinary infection. A second agent is recommended

only to provide broader coverage for potentially resistant organisms, wherenecessary.

Linezolid is the preferred therapy for ampicillin-resistant, vancomycin-resistant

Enterococcus(VRE) strains. Empiric therapy with a carbapenem is recommended for

ESBL-producing E coliand K pneumoniae. The optimal treatment of urinary tract infec-

tion for carbapenemase-producing organisms, including KPC or NDM-1 producers, is

not known. These strains are often susceptible only to tigecycline or colistimethate,



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neither of which is excreted into the urine. Case reports describe cure of patients with

urinary infection with both of these agents, but these are uncommon cases such as

prostatitis40 or patients receiving concomitant antimicrobials.41 If the strain remains

susceptible to an aminoglycoside, this would be appropriate therapy. Combinations

of antibiotics, such as a carbapenem with fosfomycin or an aminoglycoside, have

been suggested for therapy of carbapenemase producers; however, there is limitedexperience in treatment of urinary infection.

Fungal Infection

Fluconazole and amphotericin B deoxycholate are recommended for treatment of

fungal urinary infection because both these antifungals have good renal excretion.42

Other azoles (itraconazole, voriconazole, posaconazole), echinocandins (caspofungin,

micafungin, anidulafungin), and amphotericin B lipid formulations are not excreted into

the urine and are not recommended. Fluconazole is the treatment of choice. When

Candida spp resistant to fluconazole are isolated, amphotericin B-deoxycholate is

recommended. For some strains, 5-flucytosine is also effective but requires moni-toring to prevent potential hematologic toxicity, and is problematic to dose effectively

and safely in individuals with renal impairment.

Specific Therapy

A bacteriologic diagnosis for urinary infection is usually available 48 to 72 hours

following the collection of microbiology specimens. The empiric antimicrobial regimen

Table 4

Antimicrobial regimens for empiric treatment of life-threatening urinary tract infections

Antimicrobial Dosea Comment

Gentamicin ampicillin 2 g q4 h 35 mg/kg/d Ampicillin provides enterococcal

coverageTobramycin ampicillin 7 mg/kg q24 hAmikacin ampicillin 15 mg/kg q24 h

Ceftriaxone 2 g q12 h No enterococcal coverageCefotaxime 2 g q68 h

Ceftazidime 12 g q8 h No enterococcal coverage;P aeruginosacoverage

Piperacillin/tazobactam 3.35 g q6 h Enterococcal andP aeruginosacoverage

Levofloxacin 750 mg q24 h Increasing resistance observed

Ciprofloxacin 400 mg bid q24 hImipenem 500 mg q6 h ESBL andP aeruginosacoverageMeropenem 500 mg q6 h or 1 g q8 hDoripenem 500 mg q6 h

Ertapenem 1 g q24 h ESBL coverage, noP aeruginosacoverage

Aztreonam 1 g q12 h Enterobacteriaceae andP aeruginosacoverage

Vancomycin 1 g q12 h Susceptible gram-positive organisms

Abbreviation:ESBL, extended spectrum beta-lactamase.a Assumes normal renal function.From Calandra T, Cohen J, International Sepsis Forum Definition of Infection in the ICU

Consensus Conference. The international sepsis forum consensus conference on definitions ofinfection in the intensive care unit. Crit Care Med 2005;33:153848; with permission.

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Table 5

Mortality outcomes for patients with life-threatening urinary tract infection and other

infection sources of septic shock

Population (Reference)

Mortality (Days from Onset)

Urosepsis Other SourcesCritical care admissions with septic

shock; Canada, United States,Saudi Arabia2

17.9% (28 d) Pneumonia: 35.8%Intraabdominal: 37.3%Bloodstream: 39.6%

Severe sepsis critical care units,France4

23% (in hospital) Pneumonia: 34.7%Intraabdominal: 31.2%Bloodstream: 38%

Bacteremic pyelonephritis,Korea12

25.9% (7 d)

Elderly, bacteremic UTI, Korea20 11.6% (in hospital)

Elderly (>75 y), bacteremia UTI,Israel21

33% (in hospital)

P mirabilisUTI bacteremia,Taiwan10

28.6% (in hospital)

Proteeae bacteremia, Korea47 9.1% (30 d) Primary bacteremia: 34.5%SST: 45.5%Biliary: 10.8%

E colibacteremic UTI, Denmark24 12% (in hospital)HA: 24%CA: 10%

HCA-BSI UTI, Canada

18

15% (30 d) All BSI sources: 22%ESBL bacteremia UTI, Taiwan,11 23.1% (30 d)

HCA, gram-negative bacteremiasepsis, Singapore48

12.1%; OR 0.44 (0.250.77)vs other site (30 d)

Intraabdominal: 13%Pneumonia: 53.3%SST: 25%

Community onset bacteremic UTI,Taiwan8

ESBL: 8.3% (21 d)Non-ESBL: 4.4%

Community onset bacteremia,UK49

11.2% (30 d)OR 0.26 (0.14, 0.48) vs

other sites

ESBL bacteremia, India50 UTI: 16.4% (14 d);OR 0.40 (0.17, 0.96) vs

other sites

Intraabdominal: 38.4%Pneumonia: 71.4%Undetermined: 20.5%

Nationwide surveillancebacteremic urinary infection,Korea15

10.6% (30 d)HCA 21%CA 8.3%

Bacteremic, emergency, Taiwan51 4.7% (28 d) reference Pneumonia 40.4%(OR 13.77; 6.18, 30.71)vs UTI

Intraabdominal 44.1%(OR 16.05; 6.59, 39.14)

Primary bacteremia 15.9%(3.83; 1.67; 8.78)

Abbreviations: BSI, bloodstream infection; CA, community-acquired; HA, hospitalacquired; SST,skin and soft tissue.

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antimicrobial therapy is not effective in preventing symptomatic urinary infection in pa-

tients with complicated urinary infection and is not indicated.

OUTCOMES

The mortality for patients admitted to critical care units with septic shock from a uri-nary source is reported to be 10% to 20%. This rate is consistently lower than the

30% to 40% mortality reported for other common sources of septic shock

(Table 5). The lower risk of mortality may reflect the relative straightforward approach

to source control for many patients with urinary infection. A urinary source of sepsis is

also less frequently complicated by adult respiratory distress syndrome (ARDS). In a

US facility, 549 (27.8%) of 1973 patients admitted to critical care units with bacter-

emia, pneumonia, or sepsis developed ARDS compared with only 4.7% of those pa-

tients with urosepsis (OR 0.43; 95% CI: 0.270.68).52

The mortality of patients with bacteremic urinary infection is significantly lower for

hospital-acquired compared with community-acquired infection, and also varieswith the organism isolated (see Table 5; Table 6). Risk factors for mortalityreported

in multivariate analyses are summarized in Table 6. Chin and colleagues20 also re-

ported that, in elderly Koreans with bacteremic urinary infection, in-hospital mortality

was 57.1% for gram-positive organisms but only 7.6% for gram negative organisms.

Chang and colleagues19 reported the case fatality rate for hospital-acquired urinary

tractrelated bloodstream infection was 32.8% (95% CI 27.7%38.2%).E colihad a

lower case fatality rate, 14.6%, than all other gram-negative organisms isolated.

The case fatality rate was 31.9% forEnterococcus(42.3% for VRE and 17.9% for van-

comycin-susceptible), 49.2% forCandida spp, 34.6% forPseudomonas spp, 42.9%

for coagulase-positive staphylococcus, and 33.3% for Klebsiella spp.

Other potential morbidity includes renal impairment and, for bacteremic patients,

metastatic infection. Urinary tract infection, by itself, seldom causes renal failure.

The prognosis for renal functional impairment usually depends on premorbid renal

function; concomitant illnesses, such as diabetes; and recovery following relief of

Table 6

Risk factors for mortality identified in studies of bacteremic urinary tract infection

Reference Multivariate Risk Factors: HR (95% CI)United States19 Age/10 y, 1.63 (1.372.00)

CA vs HCA, 0.26 (0.140.44)E colivs other 0.39 (0.170.88)

Canada, CA-UTI18 Age, 1.02 (1.001.03)Teaching hospital, 0.62 (0.420.94)Hematology malignancy, 3.00 (1.575.75)Other neoplasia, 1.88 (1.222.89)Foley catheter, 1.85 (1.143.00)S aureus,2.01 (1.073.77)

ESBL urosepsis, Taiwan11 Male, 0.8 (0.010.79)

Bacteremia score 4, 20.55 (3.31127.37)Shock, 9.86 (1.1783.01)Neurologic failure, 11.29 (1.6278.88)

Elderly, bacteremic UTI, Korea20 Functional dependency, 10.9 (2.254.6)Low serum albumin, 27.0 (2.0361.2)

Abbreviations: CA, community-acquired; CA-UTI, catheter-acquired urinary tract infection; HCA,health careacquired.



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obstruction or sepsis-related renal impairment. The most common site of metastatic

infection is the vertebral column. Endocarditis, other bone and joint infections, other

endovascular infections with prosthetic devices, and endophthalmitis may also occur.

These infections may not become apparent for weeks after the initial infection.

SUMMARY

The urinary tract is a common source for life-threatening infections. Most patients with

sepsis or septic shock from a urinary source have complicated urinary tract infection.

Obstruction or mucosal trauma are the most common precipitating events. Effective

management requires prompt assessment, appropriate collection of microbiology

specimens, prompt initiation of antimicrobial therapy, source control where appro-

priate, and supportive therapy as required. For empiric antimicrobial therapy, an agent

excreted by the kidneys with broad antimicrobial coverage should be initiated. Pa-

tients with obstruction or abscesses may require source control. Mortality with septic

shock from a urinary source is reported to be 10% to 20%. This is consistently lowerthan mortality with septic shock complicating infections from the lungs or intraabdo-

minal abscesses.

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