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Infectious Diseases Society of America Guidelinesfor the Diagnosis and Treatment of AsymptomaticBacteriuria in Adults Lindsay E. Nicolle,1 Suzanne Bradley,2 Richard Colgan,3 James C. Rice,4 Anthony Schaeffer,5 and Thomas M. Hooton6
1University of Manitoba, Winnipeg, Canada; 2University of Michigan, Ann Arbor; 3University of Maryland, Baltimore; 4University of Texas,Galveston; 5Northwestern University, Chicago, Illinois; and 6University of Washington, Seattle SUMMARY OF RECOMMENDATIONS
• Periodic screening for recurrent bacteriuria The diagnosis of asymptomatic bacteriuria should should be undertaken following therapy (A-III).
be based on results of culture of a urine specimen col- • No recommendation can be made for or against lected in a manner that minimizes contamination (A-II) repeated screening of culture-negative women in For asymptomatic women, bacteriuria is definedas 2 consecutive voided urine specimens with Screening for and treatment of asymptomatic bac- isolation of the same bacterial strain in quanti- teriuria before transurethral resection of the prostate is A single, clean-catch voided urine specimen with An assessment for the presence of bacteriuriashould be obtained, so that results will be avail- 1 bacterial species isolated in a quantitative countу able to direct antimicrobial therapy prior to the 105 cfu/mL identifies bacteriuria in men (B- • Antimicrobial therapy should be initiated shortly A single catheterized urine specimen with 1 bac- terial species isolated in a quantitative countу • Antimicrobial therapy should not be continued 102 cfu/mL identifies bacteriuria in women or after the procedure, unless an indwelling catheter Pyuria accompanying asymptomatic bacteriuria is Screening for and treatment of asymptomatic bac- not an indication for antimicrobial treatment (A-II).
teriuria is recommended before other urologic proce- Pregnant women should be screened for bacte- dures for which mucosal bleeding is anticipated (A-III).
riuria by urine culture at least once in early pregnancy, Screening for or treatment of asymptomatic bac- and they should be treated if the results are positive teriuria is not recommended for the following persons.
• Premenopausal, nonpregnant women (A-I).
The duration of antimicrobial therapy should be • Older persons living in the community (A-II).
Received 29 October 2004; accepted 2 November 2004; electronically published • Elderly, institutionalized subjects (A-I).
• Persons with spinal cord injury (A-II).
These guidelines were developed and issued on behalf of the Infectious Diseases Society of America and have been endorsed by the American Society • Catheterized patients while the catheter remains of Nephrology and the American Geriatric Society.
Correspondence: Dr. Lindsay E. Nicolle, University of Manitoba, Health Sciences Centre, Rm. GG443, 820 Sherbrook St., Winnipeg, MB R3A 1R9, Canada Antimicrobial treatment of asymptomatic wo- men with catheter-acquired bacteriuria that persists Clinical Infectious Diseases
2005; 40:643–54
48 h after indwelling catheter removal may be con- ᮊ 2005 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2005/4005-0001$15.00 IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March) • 643
No recommendation can be made for screening for or DEFINITIONS
treatment of asymptomatic bacteriuria in renal transplant or “Asymptomatic bacteriuria,” or asymptomatic urinary infec- other solid organ transplant recipients (C-III).
tion, is isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from aperson without symptoms or signs referable to urinary infection The purpose of this guideline is to provide recommendations [3]. “Acute uncomplicated urinary tract infection” is a symp- for diagnosis and treatment of asymptomatic bacteriuria in tomatic bladder infection characterized by frequency, urgency, adult populations 118 years of age. The recommendations were dysuria, or suprapubic pain in a woman with a normal geni- developed on the basis of a review of published evidence, with tourinary tract, and it is associated with both genetic and be- the strength of the recommendation and quality of the evidence havioral determinants [4]. “Acute nonobstructive pyelone- graded using previously described Infectious Diseases Society phritis” is a renal infection characterized by costovertebral angle of America (IDSA) criteria (table 1) [1]. Recommendations are pain and tenderness, often with fever; it occurs in the same relevant only for the treatment of asymptomatic bacteriuria and population that experiences acute uncomplicated urinary in- do not address prophylaxis for prevention of symptomatic or fection. “Complicated urinary tract infection,” which may in- asymptomatic urinary infection. This guideline is not meant volve either the bladder or kidneys, is a symptomatic urinary infection in individuals with functional or structural abnor- Screening of asymptomatic subjects for bacteriuria is appro- malities of the genitourinary tract [5]. Uncomplicated urinary priate if bacteriuria has adverse outcomes that can be prevented infection occurs rarely in men, and urinary infection in men by antimicrobial therapy [2]. Outcomes of interest are short is usually considered complicated. A “relapse” is a recurrent term, such as symptomatic urinary infection (including bac- urinary tract infection after therapy resulting from persistence teremia with sepsis or worsening functional status), and longer of the pretherapy isolate in the urinary tract. “Reinfection” is term, such as progression to chronic kidney disease or hyper- recurrent urinary tract infection with an organism originating tension, development of urinary tract cancer, or decreased du- from outside of the urinary tract, either a new bacterial strain ration of survival. Treatment of asymptomatic bacteriuria may or a strain previously isolated that has persisted in the colo- itself be associated with undesirable outcomes, including sub- nizing flora of the gut or vagina [4]. “Pyuria” is the presence sequent antimicrobial resistance, adverse drug effects, and cost.
of increased numbers of polymorphonuclear leukocytes in the If treatment of bacteriuria is not beneficial, screening of asymp- urine and is evidence of an inflammatory response in the uri- tomatic populations to identify bacteriuria is not indicated, unless performed in a research study to further explore thebiology or clinical significance of bacteriuria. Thus, there are LITERATURE REVIEW
2 topics of interest: whether asymptomatic bacteriuria is as-sociated with adverse outcomes, and whether the interventions The recommendations in this guideline were developed after a of screening and antimicrobial treatment improve these review of studies published in English. These were identified through a search of the PubMed database supplemented by Infectious Diseases Society of America–US Public Health Service Grading System for ranking recommendations
in clinical guidelines.
Good evidence to support a recommendation for use; should always be offered Moderate evidence to support a recommendation for use; should generally be offered Poor evidence to support a recommendation; optional Moderate evidence to support a recommendation against use; should generally not be offered Good evidence to support a recommendation against use; should never be offered Evidence from у1 properly randomized, controlled trial Evidence from у1 well-designed clinical trial, without randomization; from cohort or case- controlled analytic studies (preferably from 11 center); from multiple time-series; or fromdramatic results from uncontrolled experiments Evidence from opinions of respected authorities, based on clinical experience, descriptive 644 • CID 2005:40 (1 March) • Nicolle et al.
review of references of relevant papers to identify additional were symptomatic [18]. If urine specimens are collected using reports, particularly early studies not accessed through the a freshly applied condom catheter and leg bag, however, у105 PubMed search. In addition, experts in urinary infection were cfu/mL is the appropriate quantitative criterion, with 90% va- asked to identify any additional trials not accessed through lidity for identifying asymptomatic bacteriuria in the voided review. Clinical studies include prospective, randomized clinical specimen, compared with a paired catheterized specimen [19, trials; prospective cohort studies; case-control studies; and 20]. With single urine specimens obtained by urethral cathe- other descriptive studies. When appropriate, the methodolog- terization, lower quantitative counts of у102 cfu/mL are con- ical rigor of studies was evaluated using accepted criteria (e.g., sistent with bacteriuria for both men and women [21, 22].
the CONSORT statement [7]). Studies were excluded if the Patients who have chronic kidney disease, who are experiencing study population was not adequately characterized to assess diuresis, or who are infected with selected fastidious organisms generalizability, if procedures for patient follow-up or exclu- may have bacteriuria with lower quantitative counts in voided sions may have introduced sufficient bias to limit the credibility specimens, but the criteria for bacteriuria in such patients are of observations, or if there were insufficient numbers of patients enrolled to support valid statistical analysis.
Pyuria is evidence of inflammation in the genitourinary tract and is common in subjects with asymptomatic bacteriuria [13, DIAGNOSIS
24–27]. Pyuria is present with asymptomatic bacteriuria in∼32% of young women [13], 30%–70% of pregnant women Asymptomatic bacteriuria is a microbiologic diagnosis deter- [25, 26], 70% of diabetic women [24], 90% of elderly insti- mined with a urine specimen that has been collected in a man- tutionalized patients [27], 90% of hemodialysis patients [28], ner to minimize contamination and transported to the labo- 30%–75% of bacteriuric patients with short-term catheters in ratory in a timely fashion to limit bacterial growth. The usual place [29], and 50%–100% of individuals with long-term in- quantitative definition is у105 cfu/mL in 2 consecutive urine dwelling catheters in place [30]. Pyuria also accompanies other specimens [3], initially proposed after studies performed in the inflammatory conditions of the genitourinary tract in patients 1940s and 1950s [8, 9]. In these studies, a bacterial count of with negative urine culture results. These may be either infec- у105 cfu/mL in a clean, voided specimen was confirmed by a tious, such as renal tuberculosis and sexually transmitted dis- concomitant count in a catheterized specimen in 195% of sub- eases, or noninfectious, such as interstitial nephritis. Thus, by jects in several asymptomatic clinical groups, whereas lower itself, the presence of pyuria is not sufficient to diagnose bac- quantitative counts in the voided specimen were not usually teriuria, and the presence or absence of pyuria does not dif- confirmed by the catheterized specimen [8]. When the screen- ferentiate symptomatic from asymptomatic urinary infection.
ing of asymptomatic women using multiple voided specimens Recommendation.
was evaluated, bacteriuria documented in an initial voided riuria should be based on culture of a urine specimen collected urine specimen was confirmed in a second voided specimen, in a manner that minimizes contamination (A-II).
usually obtained several days later, only 80% of the time. If 2successive bacteriuric voided specimens had similar positive • For asymptomatic women, bacteriuria is defined as 2 con- culture results, a third consecutive specimen also yielded con- secutive voided urine specimens with isolation of the same sistent results in 95% of cases [9, 10]. Some studies involving bacterial strain in quantitative counts of у105 cfu/mL (B-II).
women have used a more restrictive criterion of 3 consecutive • A single, clean-catch, voided urine specimen with 1 bacterial voided urine specimens collected over 3 weeks with consistent species isolated in a quantitative count of у105 cfu/mL iden- bacteriologic results [11, 12], whereas other studies have used tifies bacteriuria in asymptomatic men (B-III).
a more permissive criterion of a single positive urine specimen • A single catheterized urine specimen with 1 bacterial species yielding у105 cfu/mL [13, 14]. Because transient bacteriuria is isolated in a quantitative count of у102 cfu/mL identifies common in healthy young women [13, 15, 16], the prevalence will be lower if 11 specimen is required for identification ofbacteriuria [13].
Pyuria accompanying asymptomatic bacteriuria is not an in- Microbiologic criteria for diagnosis of asymptomatic bac- dication for antimicrobial treatment (A-II).
teriuria in men are not as well validated. The finding of a single PREVALENCE OF ASYMPTOMATIC
voided urine specimen with у105 cfu/mL of an Enterobacter- BACTERIURIA
iaceae was reproducible in 98% of asymptomatic ambulatorymen when the culture was repeated within 1 week [17]. A Asymptomatic bacteriuria is common, but the prevalence in voided specimen with the lower quantitative count of у103 populations varies widely with age, sex, and the presence of cfu/mL was 97% sensitive and 97% specific for identification genitourinary abnormalities (table 2). For healthy women, the of bacteriuria in ambulatory men, but most of these patients prevalence of bacteriuria increases with advancing age, from IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March) • 645
Prevalence of asymptomatic bacteriuria in selected populations.
Elderly persons in a long-term care facility Sphincterotomy and condom catheter in place ∼1% among schoolgirls to 120% among healthy women у80 five percent to 50% of elderly women and 15%–40% of elderly years of age living in the community [31]. The prevalence of men in long-term care facilities are bacteriuric [27]. The ma- bacteriuria among young women is strongly associated with jority of these elderly persons have chronic neurologic illnesses, sexual activity. It was 4.6% among premenopausal married with the highest prevalence of bacteriuria observed in the most women but only 0.7% among nuns of similar age [12]. Pregnant highly functionally impaired residents. The clinical assessment and nonpregnant women have a similar prevalence of bacte- of elderly bacteriuric residents to ascertain the presence or ab- riuria (2%–7%) [31]. Bacteriuria is more common in diabetic sence of symptoms may be problematic, and observations of women, with a prevalence of 8%–14%, and is usually correlated cloudy or smelly urine by themselves should not be interpreted with duration of diabetes and presence of long-term compli- as indications of symptomatic infection [39]. Use of a long- cations of diabetes, rather than with metabolic parameters of term indwelling catheter [22] or permanent ureteric stent [40] diabetic control [36]. Asymptomatic bacteriuria is rare in is associated with bacteriuria virtually 100% of the time.
healthy young men [37]. The prevalence in men increases sub-stantially after the age of 60 years, presumably because of ob- MICROBIOLOGY OF ASYMPTOMATIC
structive uropathy and voiding dysfunction associated with pro- BACTERIURIA
static hypertrophy [27, 37]. From 6% to 15% of men 175 yearsof age who reside in the community are bacteriuric [31]. Di- Escherichia coli remains the single most common organism iso- abetic men do not appear to have an increased prevalence of lated from bacteriuric women [11, 12, 41], although this hap- bacteriuria, compared with nondiabetic men [32].
pens proportionally less frequently than for women with acute Many patient groups with chronic disabilities or comorbid- uncomplicated urinary tract infection. E. coli strains isolated ities characterized by impaired urinary voiding or with in- from women with asymptomatic bacteriuria are characterized dwelling urinary devices have a very high prevalence of asymp- by fewer virulence characteristics than are those isolated from tomatic bacteriuria, irrespective of sex. Patients with short-term women with symptomatic infection [42]. Other Enterobacter- indwelling urethral catheters acquire bacteriuria at the rate of iaceae (such as Klebsiella pneumoniae) and other organisms 2%–7% per day (table 2) [35, 38]. Patients with spinal cord (including coagulase-negative staphylococci, Enterococcus spe- injury have a prevalence of 150%, whether voiding is managed cies, group B streptococci, and Gardnerella vaginalis) are com- by intermittent catheterization or by sphincterotomy and con- mon as well. For men, coagulase-negative staphylococci are also dom drainage [33, 34]. Patients undergoing hemodialysis have common, in addition to gram-negative bacilli and Enterococcus a prevalence of asymptomatic bacteriuria of 28% [28]. Twenty- species [43, 44]. Subjects with abnormalities of the genitouri- 646 • CID 2005:40 (1 March) • Nicolle et al.
nary tract, including elderly institutionalized subjects, have a antoin or placebo [50]. The antibiotic group had a signifi- wide variety of organisms isolated. E. coli remains the single cantly lower prevalence of bacteriuria at 6 months but not at most common organism isolated from women, but other or- 1 year. Episodes of symptomatic infection 1 year after therapy ganisms, such as Proteus mirabilis, are more common in men occurred with a similar frequency in the treatment and pla- [27]. Men and women with a long-term urologic device in place usually have polymicrobial bacteriuria, which often in- These studies support the conclusions that healthy, bacter- cludes Pseudomonas aeruginosa and urease-producing organ- iuric, premenopausal women are at an increased risk for symp- isms, such as P. mirabilis, Providencia stuartii, and Morganella tomatic urinary infection and are more likely to have bacteriuria at follow-up. However, asymptomatic bacteriuria is not asso-ciated with long-term adverse outcomes, such as hypertension, THE MANAGEMENT OF ASYMPTOMATIC
chronic kidney disease, genitourinary cancer, or decreased du- BACTERIURIA
ration of survival. The association of asymptomatic bacteriuriawith symptomatic urinary infection is likely attributable to host Premenopausal, Nonpregnant Women
factors that promote both symptomatic and asymptomatic uri- The natural history of asymptomatic bacteriuria in premeno- nary infection, rather than symptomatic infection being attrib- pausal nonpregnant women has been described in short-term utable to asymptomatic bacteriuria. Finally, treatment of [13] and long-term [41, 45–48] prospective cohort studies. In asymptomatic bacteriuria neither decreases the frequency of young women, symptomatic urinary infection occurred sig- symptomatic infection nor prevents further episodes of asymp- nificantly more frequently in bacteriuric women than in non- bacteriuric women within 1 week after a urine culture (8% of Recommendation.
bacteriuric women became symptomatic, compared with 1% tomatic bacteriuria in premenopausal, nonpregnant women is of women without bacteriuria) [13]. The increased risk of symptomatic infection remained at 1 month after new-onsetbacteriuria [13]. Long-term cohort studies also report an in- Pregnant Women
creased frequency of symptomatic urinary infection in womenidentified with asymptomatic bacteriuria at initial screening Women identified with asymptomatic bacteriuria in early preg- [46, 47]. In a Swedish study, after 15 years of follow-up, symp- nancy have a 20–30-fold increased risk of developing pyelo- tomatic urinary infection and pyelonephritis occurred at least nephritis during pregnancy, compared with women without once in 55% and 7.5% of women with bacteriuria at enrollment, bacteriuria [26, 51–59]. These women also are more likely to respectively, and in 10% and 0% of those without bacteriuria, experience premature delivery and to have infants of low birth respectively [47]. Women with bacteriuria at enrollment were weight. Prospective, comparative clinical trials have consistently also more likely to be bacteriuric at follow-up, regardless of reported that antimicrobial treatment of asymptomatic bacte- whether antimicrobial therapy was given [41, 47, 49].
riuria during pregnancy decreases the risk of subsequent py- In 3 prospective studies from Wales and Jamaica that enrolled elonephritis from 20%–35% to 1%–4% (table 3) [60]. Meta- women aged 15–84 years, increased mortality was observed analyses of cohort studies and randomized clinical trials also among bacteriuric women [49]. The association of bacteriuria support the conclusion that antimicrobial treatment of asymp- and mortality was not as strong when the bacteriuric and non- tomatic bacteriuria decreases the frequency of low–birth weight bacteriuric groups were age- and weight-matched, and no strat- infants and preterm delivery [61, 62]. Most of these studies ification for other potential confounders was performed. In a were performed early in the antimicrobial era, with nitrofur- Swedish study that enrolled women with a median age of 58 antoin and sulfonamides being the most common antimicro- years (range, 35–72 years), there were no differences in the bials. The consistency and robustness of observations from rates of hypertension or chronic kidney disease between bac- multiple studies resulted in screening for and treatment of teriuric and nonbacteriuric women after 15 years of follow-up asymptomatic bacteriuria during pregnancy becoming a stan- [47]. In another Swedish study of women initially enrolled at dard of care in developed countries. More-recent reports of 38–60 years of age, the rates of progression to chronic kidney implementation of screening and treatment programs for disease and mortality were similar for bacteriuric and nonbac- asymptomatic bacteriuria in pregnant women report a decrease teriuric subjects after 24 years [41]. Bacteriuric women and in rates of pyelonephritis for all pregnant women, from 1.8% nonbacteriuric control subjects did not differ with regard to to 0.6% in a Spanish health care center [63], and 2.1% to 0.5% serum creatinine levels and intravenous pyelogram findings af- in a Turkish health care center [64]. These are consistent with ter 3–5 years of follow-up in an English study [48].
the early reports of benefits with screening for and treatment A prospective, controlled trial randomized bacteriuric of asymptomatic bacteriuria during pregnancy.
women to receive a 1-week course of therapy with nitrofur- In the therapeutic studies that established the benefit of treat- IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March) • 647
Findings of comparative clinical trials of antimicrobial therapy for the treatment of asymptomatic bacteriuria in pregnancy.
furantoin, or mandelamine alone;mandelamine to term a Microbiologic results from initial screening urine culture in pregnancy.
ment of asymptomatic bacteriuria during pregnancy, admin- and they should be treated if the results are positive (A-I).
istration of antimicrobial therapy usually continued for the • The duration of antimicrobial therapy should be 3–7 days duration of the pregnancy (table 3). A prospective, randomized study of continuous antimicrobial therapy to the end of preg- • Periodic screening for recurrent bacteriuria should be un- nancy compared with 14 days of nitrofurantoin or sulfameth- izole, followed by weekly urine culture screening and re-treat- • No recommendation can be made for or against routine ment if bacteriuria recurred, reported similar outcomes for the repeated screening of culture-negative women in the later 2 treatment groups [65]. A recent Cochrane systematic review concluded that there was insufficient evidence to recommend a duration of antimicrobial therapy for pregnant women among Diabetic Women
single-dose, 3-day, 4-day, and 7-day treatment regimens [66].
Prospective, cohort studies of diabetic women report no dif- Thus, the optimal duration of antimicrobial therapy for treat- ferences in rates of symptomatic urinary infection, mortality, ment of bacteriuria in pregnant women has not been or progression to diabetic complications between initially bac- teriuric and nonbacteriuric women at 18 months [70] or 14 The appropriate screening test is a urine culture [67]. Screen- years [71] of follow-up. A randomized, controlled trial of an- ing for pyuria has a low sensitivity—only ∼50% for identifi- tibiotic therapy or no therapy for diabetic women with asymp- cation of bacteriuria in pregnant women [25]. The optimal tomatic bacteriuria and continued screening for bacteriuria frequency of screening is not well defined. Women with a neg- every 3 months reported, after a maximum of 3 years of follow- ative urine culture result for a single screening specimen at 12– up, that antimicrobial therapy did not delay or decrease the 16 weeks have a 1%–2% risk of developing pyelonephritis later frequency of symptomatic urinary infection, nor did it decrease in pregnancy (table 3). What proportion of this may be pre- the number of hospitalizations for urinary infection or other vented with repeated routine screening is not known. A single causes [72]. There was no acceleration of progression of diabetic urine sample obtained for culture at week 16 of gestation was complications, such as nephropathy, in bacteriuric subjects who concluded to be optimal in a Swedish study [68]. An American did not receive antimicrobial therapy. Diabetic women who cost evaluation from the viewpoint of the outcome of pyelo- received antimicrobial therapy, however, had 5 times as many nephritis concluded that a single screening culture in the first days of antimicrobial use and significantly more adverse an- trimester was cost-effective if the prevalence of bacteriuria was timicrobial effects. Thus, there were no benefits for continued 12% and the risk of pyelonephritis in bacteriuric women was screening and treatment of asymptomatic bacteriuria in diabetic women, and there was evidence of some harm.
Recommendation.
Recommendation.
bacteriuria by urine culture at least once in early pregnancy, tomatic bacteriuria in diabetic women is not indicated (A-I).
648 • CID 2005:40 (1 March) • Nicolle et al.
Older Persons Residing in the Community
asymptomatic bacteriuria in older persons resident in the com- Large, long-term, cohort studies of asymptomatic bacteriuria have enrolled both pre- and postmenopausal women [41, 46,47, 49]. These studies uniformly report no excess adverse out- Elderly Institutionalized Subjects
comes in women with asymptomatic bacteriuria. A prospective, Prospective, randomized clinical trials of antimicrobial ther- randomized study of nitrofurantoin or placebo also enrolled apy or no therapy for elderly residents of long-term care women aged 20–65 years, with a median age between 40–49 facilities have reported no benefits of screening for or treat- years [50]. Thus, these studies report that outcomes of bac- ment of asymptomatic bacteriuria (table 4) [76–79]. There teriuria and treatment of bacteriuria in healthy postmenopausal was no decrease in the rate of symptomatic infection or im- women are similar to those observed in premenopausal, non- provement in survival [76–78], and there were no changes in chronic genitourinary symptoms [79] associated with anti- A prospective, randomized clinical trial of antimicrobial microbial therapy. Treatment of asymptomatic bacteriuria was treatment versus placebo for bacteriuria enrolled ambulatory associated with significantly increased adverse antimicrobial women who resided in a geriatric apartment facility and re- effects [76] and reinfection with organisms of increasing re- ported a decrease in the prevalence of asymptomatic bacteriuria sistance [76]. Prospective cohort studies report similar sur- at 6 months, but there was no significant difference in the vival data for long-term care facility residents with and those number of symptomatic episodes [73]. A prospective cohort without bacteriuria among women in the United States [78], study of 134 ambulatory male veterans 165 years of age ob- men in Canada [80], and women or men in Greece [81].
served for 1–4.5 years, including 29 subjects with bacteriuria, Recommendation.
reported no adverse outcomes attributable to untreated bac- tomatic bacteriuria in elderly institutionalized residents of long- teriuria [44]. Population-based cohort studies report no as- term care facilities is not recommended (A-I).
sociation between bacteriuria and survival for Swedish menand women at 5 years of follow-up [74] or Finnish men and Subjects with Spinal Cord Injuries
women aged 185 years during 5 years of follow-up [75].
Subjects with spinal cord injuries have a high prevalence of Recommendation.
bacteriuria, and they also experience a high incidence of symp- Randomized clinical trials of treatment of asymptomatic bacteriuria in elderly populations.
given for symptomatic UTI, 16.4%vs. 7.9% (P p patient-year for the therapy group(P p Ϫ0.05 to +0.47); therapy recipi-ents had significantly more ad-verse drug-related events and rein-fections with resistant organisms cin administered every 14 days;cultures were performed every6 months RR, relative risk; TMP, trimethoprim; UTI, urinary tract infection.
a Data are mean age, unless otherwise indicated.
b Median age.
IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March) • 649
tomatic urinary infection [34, 82]. When asymptomatic bac- guria 2 weeks after therapy for catheterized subjects and no teriuria was uniformly treated in a cohort of catheter-free, pri- clinical benefits of treatment [94].
marily male, spinal cord–injured subjects, early recurrence of A prospective, randomized, placebo-controlled trial of an- bacteriuria after therapy was the usual outcome. After 7–14 timicrobial treatment of asymptomatic bacteriuria persisting 48 days of antibiotic therapy, 93% of subjects were again bacter- h after removal of short-term catheters in women with catheter- iuric by 30 days after completion of therapy, and after a 28- acquired bacteriuria reported significantly improved microbi- day course of antibiotic therapy, 85% were bacteriuric by 30 ologic and clinical outcomes at 14 days in treated women [95].
days [83]. Reinfecting strains showed increased antimicrobial Although 15 (36%) of 42 women randomized to receive no resistance. When 52 patients with a relatively recent onset of therapy had spontaneous microbiologic resolution by 14 days, spinal cord injury were observed prospectively for 4–26 weeks, 7 (17%) developed symptoms. No women in the treatment the results of 78% of weekly urine cultures were positive, but group became symptomatic. This study enrolled a selected only 6 symptomatic episodes occurred, all of which responded group of hospitalized women characterized by being relativelyyoung (median age, 50 years) and experiencing a short period promptly to antimicrobial treatment [84]. In a small, random- of catheterization (median duration, 3 days).
ized, placebo-controlled trial, rates of symptomatic urinary in- Long-term catheters.
fection and recurrence of bacteriuria were similar among re- cephalexin therapy versus no antibiotic therapy for bacteriuric cipients of either antimicrobial or placebo for patients with patients with long-term indwelling urethral catheters in place bladder emptying managed by intermittent catheterization [85].
and drug-susceptible organisms isolated reported a similar in- A prospective, randomized trial of antimicrobial treatment or cidence of fever among both treated and untreated patients no treatment of asymptomatic bacteriuria enrolled 50 patients observed for 12–44 weeks [96]. Rates of reinfection were also who were treated with intermittent catheterization and reported similar, but 75% of reinfecting organisms in the control group a similar frequency of symptomatic urinary infection during remained susceptible to cephalexin, compared with only 36% an average of 50 days of follow-up, irrespective of whether in the cephalexin treatment group. A prospective, noncom- prophylactic antimicrobials were given [86]. Although there parative study of consecutive courses of antimicrobial treatment have been a limited number of clinical trials, and although to eradicate bacteriuria in elderly patients with long-term cath- interpretation of results is compromised by relatively short du- eters reported no decrease in the number of episodes of fever rations of follow-up and small study numbers, review articles with treatment, compared with the pretreatment period, and [87, 88] and consensus guidelines [89] uniformly recommend there was immediate recurrence of bacteriuria after therapy, treatment only of symptomatic urinary tract infection in pa- often with organisms of increasing resistance [97].
Recommendation.
Recommendation.
should not screened for or treated in patients with an indwelling screened for or treated in spinal cord–injured patients (A-II).
Patients with Indwelling Urethral Catheters
• Antimicrobial treatment of asymptomatic womenwithcath- eter-acquired bacteriuria that persists 48 h after catheter Short-term catheters.
cility patients with short-term (!30 days) indwelling urethralcatheters receive antimicrobial therapy, usually for an indicationother than urinary infection [90, 91]. This high frequency of Urologic Interventions
concurrent antimicrobial use makes assessment of outcomes Patients with asymptomatic bacteriuria who undergo traumatic unique to treatment of asymptomatic bacteriuria problematic.
genitourinary procedures associated with mucosal bleeding have A prospective, cohort study of 235 catheter-acquired infections a high rate of postprocedure bacteremia and sepsis. Bacteremia among 1497 patients, 90% of whom were asymptomatic, re- occurs in up to 60% of bacteriuric patients who undergo tran- ported only 1 secondary bloodstream infection [92]. A case- surethral prostatic resection, and there is clinical evidence of control study reported that acquisition of bacteriuria with in- sepsis in 6%–10% of these persons [98]. Retrospective analysis dwelling urethral catheterization increased mortality 3-fold, but [99] and prospective, randomized clinical trials [100–103] sup- the explanation for this association was not clear, and multi- port the effectiveness of antimicrobial treatment in preventing variate analysis found that antimicrobial therapy did not alter these complications in bacteriuric men undergoing transurethral the association with mortality [93]. A prospective, randomized, resection of the prostate. In one comparative trial, the efficacy placebo-controlled trial of treatment of funguria in 313 pa- of cefotaxime was superior to that of methenamine mandelate tients, more than one-half of whom had indwelling urethral [101]. There is little information relevant to other procedures, catheters in place, showed no differences in eradication of fun- but any intervention with a high probability of mucosal bleeding 650 • CID 2005:40 (1 March) • Nicolle et al.
should be considered a risk [104]. Pretreatment of asymptomatic rather than bacteriuria [113]. Thus, with current management bacteriuria is not beneficial for all invasive procedures. For in- strategies, screening for bacteriuria is unlikely to provide a ben- stance, replacement of a long–term indwelling foley catheter is efit. Some experts do recommend screening for bacteriuria, at associated with a low risk of bacteremia, and antimicrobial treat- least for the first 6 months after renal transplantation [114].
Recent guidelines for outpatient surveillance of renal transplant The appropriate timing for initiation of antimicrobial ther- recipients, however, make no recommendation for screening apy is not well defined. Although 72 h before the intervention has been suggested [107], this is likely to be excessive and allows Screening for or treatment of bacteriuria has not been eval- the opportunity for superinfection before the procedure. Ini- uated for other solid organ transplant recipients. Guidelines tiation of therapy the night before or immediately before the for infection prevention in bone marrow transplant recipients procedure is effective [99, 103]. The optimal time to obtain a make no recommendation for screening for bacteriuria [117].
sample for culture before the procedure and the duration of A small study of women with primary biliary cirrhosis and antimicrobial therapy are also not addressed in clinical trials.
bacteriuria randomized to receive either antimicrobial therapy In the absence of an indwelling catheter, antimicrobial therapy or no antimicrobial therapy reported no differences in the time can likely be discontinued immediately after the procedure [99, to reinfection or the number of reinfections in the 2 groups 102, 103]. When an indwelling catheter remains in place after [118]. Limited studies involving HIV-infected patients have re- a prostatic resection, it has been recommended by some in- ported no association between asymptomatic bacteriuria and vestigators that antimicrobial therapy be continued until the HIV infection in women, but there was an increased prevalence of bacteriuria among HIV-infected men that was inversely cor- Recommendation.
related with CD4+ cell counts [30]. Adverse clinical outcomes tomatic bacteriuria before transurethral resection of the pros- associated with bacteriuria in these populations have not been Recommendations.
• An assessment for the presence of bacteriuria should be screening for or treatment of asymptomatic bacteriuria in renal obtained, so results will be available to direct antimicrobial transplant or other solid organ transplant recipients (C-III).
therapy prior to the procedure (A-III).
• Antimicrobial therapy should be initiated shortly before the Asymptomatic bacteriuria is common. Pregnant women with Antimicrobial therapy should not be continued beyond the asymptomatic bacteriuria are at an increased risk for adverse procedure, unless an indwelling catheter remains in place outcomes, and these can be prevented with antimicrobial treat- ment of asymptomatic bacteriuria. Thus, pregnant women Screening for and treatment of asymptomatic bacteriuria is should be screened for bacteriuria and treated if test results are recommended before other urologic procedures in which mu- positive. Asymptomatic bacteriuria is also a risk for patients cosal bleeding is anticipated (A-III).
who undergo traumatic urologic interventions with mucosalbleeding, and such patients should be treated prior to such Immunocompromised Patients and Other Patients
interventions. For all other adult populations, asymptomatic Cohort studies performed early in the transplantation era re- bacteriuria has not been shown to be harmful. Although per- ported a high prevalence of asymptomatic bacteriuria among sons with bacteriuria are at an increased risk of symptomatic renal transplant recipients, especially in the first 6 months after urinary infection, treatment of asymptomatic bacteriuria does transplantation [108, 109]. Evolution in management of trans- not decrease the frequency of symptomatic infection or improve plantation has introduced routine perioperative prophylaxis, other outcomes. Thus, in populations other than those for minimization of use of indwelling urethral catheters, and long- whom treatment has been documented to be beneficial, screen- term antimicrobial prophylaxis to prevent pneumonia and ing for or treatment of asymptomatic bacteriuria is not ap- other infections. These interventions also prevent both asymp- propriate and should be discouraged.
tomatic bacteriuria and symptomatic urinary infection [110, RESEARCH PRIORITIES
111]. Recent studies, including a retrospective chart review[112] and a prospective cohort study [113], have not reported Many issues relevant to asymptomatic bacteriuria require fur- an association between asymptomatic bacteriuria and graft sur- ther research and evaluation in appropriately conducted clinical vival. Transplant recipients with urinary infection and poor graft outcome are also characterized by urologic abnormalitiesand are identified by episodes of symptomatic urinary infection, • Exploration of the clinical and microbiologic implications, IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March) • 651
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bacteriuria in men: specimen collection and culture interpretation. J
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We thank the following individuals for review and helpful suggestions 19. Ouslander JG, Greengold BA, Silverblatt FJ, Garcia JP. An accurate in the development of this guideline: Elias Abrutyn, Diana Cardenas, Ste- method to obtain urine for culture in men with external catheters.
phan Fihn, Kalpana Gupta, Jeremy Hamilton-Miller, Godfrey Harding, Arch Intern Med 1987; 147:286–8.
Andy Hoepelman, James R. Johnson, Calvin Kunin, Leonard Leibovici, 20. Nicolle LE, Harding GKM, Kennedy J, McIntyre M, Aoki F, Murray Benjamin Lipsky, Kurt G. Naber, Raul Raz, Allan Ronald, Thomas Russo, D. Urine specimen collection with external devices for diagnosis of Jack Sobel, Walter Stamm, Ann Stapleton, and John Warren. Expert sec- bacteriuria in elderly incontinent men. J Clin Microbiol 1988; 26:
retarial assistance was provided by Brenda DesRosiers.
Potential conflicts of interest.
from Ortho-McNeil. R.C. has received research funding from Ortho- 21. Saint SJ, Chenoweth CE. Biofilms and catheter-associated urinary tract McNeil and has served on the speakers’ bureau for Bayer. A.S. has been a infections. Infect Dis Clin North Am 2003; 17:411–32.
consultant for Ortho-McNeil, Proctor & Gamble, Gerson Lehrman Group, 22. Warren JW, Tenney JH, Hoopes JM, Muncie HL, Anthony WC. A Urologix, DepoMed, Schwarz BioSciences GmbH, and SynerMed Com- prospective microbiologic study of bacteriuria in patients with munications. T.M.H. has been a consultant for Bayer and served on the chronic-indwelling urethral catheters. J Infect Dis 1982; 146:719–23.
speakers’ bureau for Aventis, Bayer, Merck, and Pfizer.
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654 • CID 2005:40 (1 March) • Nicolle et al.

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Asia Pacific Journal of Family Medicine Volume 5 Issue 1 RESEARCH METHODOLOGY Application of research evidence in family practice: a case discussion of a patient with exacerbation of chronic obstructive pulmonary disease Department of Family and Community Medicine, UP College of Medicine and Philippine General Hospital, Manila, The Philippines Introduction There is a lar

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