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Home , Bacteriuria

Asymptomatic in Adults RICHARD COLGAN, M.D, University of Maryland School of Medicine, Baltimore, Maryland LINDSAY E. NICOLLE, M.D., University of Manitoba, Winnipeg, Canada ANDREW McGLONE, M.D., University of Maryland School of Medicine, Baltimore, Maryland THOMAS M. HOOTON, M.D., University of Washington School of Medicine, Seattle, Washington

A common dilemma in clinical medicine is whether to treat asymp- tomatic patients who present with in their . There are few scenarios in which treatment of asymptomatic bacter- uria has been shown to improve patient outcomes. Because of increas- ing , it is important not to treat patients with asymptomatic bacteriuria unless there is evidence of potential ben- efit. Women who are pregnant should be screened for asymptomatic bacteriuria in the first trimester and treated, if positive. Treating asymptomatic bacteriuria in patients with , older persons, patients with or without indwelling catheters, or patients with spinal cord injuries has not been found to improve outcomes. (Am Fam Physician 2006;74:985-90. Copyright © 2006 American Academy of Family Physicians.)

rinary tract infections (UTIs) with asymptomatic bacteriuria will be influ- are one of the most common enced by patient variables: healthy persons infections for which will likely have E. coli, whereas a nursing are prescribed. The Infectious home resident with a catheter is more likely to UDiseases Society of America (IDSA) issued have multi-drug–resistant polymicrobic flora guidelines for the treatment of uncomplicated (e.g., P. aeruginosa). Enterococcus species and acute bacterial cystitis and acute pyelonephri- gram-negative bacilli are common in men.9,10 tis in women.1 The presence of bacteria in the urine of an asymptomatic patient is known Diagnosis as asymptomatic bacteriuria. The IDSA also The presence of a significant quantity of bac- has published guidelines on indications for teria in a urine specimen properly collected the screening and treatment of asymptomatic from a person without symptoms or signs bacteriuria in various patient populations.2 of a UTI characterizes asymptomatic bacte- riuria.11 Quantitative criteria for identifying Epidemiology significant bacteriuria in an asymptomatic Asymptomatic bacteriuria is common, with person are: (1) at least 100,000 colony-form- varying prevalence by age, sex, sexual activity, ing units (CFUs) per mL of urine in a voided and the presence of genitourinary abnormali- midstream clean-catch specimen; and (2) at ties (Table 13-8). In healthy women, the preva- least 100 CFUs per mL of urine from a cath- lence of bacteriuria increases with age, from eterized specimen9,12,13 (Table 2). Accord- about 1 percent in females five to 14 years ing to the IDSA guideline, the diagnosis of age to more than 20 percent in women at of asymptomatic bacteriuria in women is least 80 years of age living in the community.3 appropriate only if the same species is pres- is the most common organ- ent in quantities of at least 100,000 CFUs ism isolated from patients with asymptomatic per mL of urine in at least two consecutive bacteriuria. Infecting organisms are diverse voided specimens.2,3 and include Enterobacteriaceae, Pseudomonas The and nitrite tests aeruginosa, Enterococcus species, and group B often are used in primary care settings to . Organisms isolated in patients evaluate urinary symptoms; however, they

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence Clinical recommendation rating References

Pregnant women should be screened for asymptomatic bacteriuria A 23, 24 in the first trimester of . Pregnant women who have asymptomatic bacteriuria should be B 2 treated with antimicrobial therapy for three to seven days. accompanying asymptomatic bacteriuria should not be C 3, 14 treated with antimicrobial therapy.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi- dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 906 or http://www.aafp.org/afpsort.xml.

are not useful for diagnosing UTI in an other inflammatory disorders of the geni- asymptomatic patient. A urine dipstick leu- tourinary tract (e.g., vaginitis). Urinalysis kocyte esterase test showing trace or more with microscopic examination for bacteria white blood cells has a sensitivity of 75 to remains a useful test for the identification 96 percent and specificity of 94 to 98 per- of bacteriuria. cent for detecting pyuria14; however, pyuria Limitations of the dipstick nitrite test is not specific for UTI and may occur with in diagnosing bacteriuria include: infec- tion with non-nitrite–producing pathogens; delays between obtaining and testing the TABLE 1 sample; and insufficient time since the last Prevalence of Asymptomatic Bacteriuria void for nitrites to appear at detectable lev- in Selected Populations els. Combining the leukocyte esterase and nitrite tests results in higher specificity than Population Prevalence (%) using either test alone. Healthy premenopausal women3 1.0 to 5.0 Premenopausal, Nonpregnant Women Pregnant women3 1.9 to 9.5 Postmenopausal women (50 to 70 years of age)3 2.8 to 8.6 Premenopausal, nonpregnant women with Patients with diabetes asymptomatic bacteriuria experience no Women4 9.0 to 27.0 adverse effects and usually will clear their Men4 0.7 to 1.0 bacteriuria spontaneously. However, these Older community-dwelling patients women are more likely to experience subse- Women (older than 70 years)3 > 15.0 quent symptomatic UTI than women who 15 Men4 3.6 to 19.0 do not have asymptomatic bacteriuria. Older long-term care residents One study randomized women with bacte- Women4 25.0 to 50.0 riuria to receive one week of Men4 15.0 to 40.0 (Furadantin) or placebo; those receiving the Patients with spinal cord injuries antibiotic had a significantly lower preva- Intermittent catheter5 23.0 to 89.0 lence of bacteriuria at six months, but not 16 Sphincterotomy and condom catheter6 57.0 at one year. The patients treated with Patients undergoing hemodialysis7 28.0 antibiotics were just as likely as those in the Patients with an indwelling catheter placebo arm to have a symptomatic UTI Short-term8 9.0 to 23.0 in the year after therapy. Although women Long-term8 100 with asymptomatic bacteriuria are more likely to have subsequent symptomatic UTIs, Information from references 3 through 8. treatment of asymptomatic bacteriuria does not decrease the frequency of symptomatic

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or trimethoprim/sulfamethoxazole (TMP/ TABLE 2 SMX; Bactrim, Septra) compared with those Diagnostic Criteria for treated with continuous antimicrobial ther- Asymptomatic Bacteriuria apy to the end of pregnancy.20 The IDSA recommends a course of three to seven Midstream clean-catch urine specimen: days of antimicrobial therapy for pregnant For women, two consecutive specimens with women with asymptomatic bacteriuria.2 A of the same species in quantitative Cochrane systematic review found insuffi- counts of at least 100,000 CFUs per mL of urine. cient evidence to determine whether a single For men, a single specimen with one bacterial dose regimen is as effective as treatments of species isolated in a quantitative count of at longer duration.21 least 100,000 CFUs per mL. Because leukocyte esterase and nitrite Catheterized urine specimen: tests have low sensitivity for identifying In women or men, a single specimen with one bacteriuria in women who are pregnant, bacterial species isolated in a quantitative these patients should be screened with urine count of at least 100 CFUs per mL. cultures22; however, the optimal frequency of urine culture screening has not been CFU = colony-forming unit. established. A single urine culture at the end of the first trimester generally is recom- mended based on clinical outcomes and cost- UTI or prevent further episodes of bacte- effectiveness.23,24 Women with asymptomatic riuria. Asymptomatic bacteriuria has not bacteriuria or symptomatic UTI during preg- been shown to be associated with detri- nancy should be treated (Table 3) and should mental long-term outcomes (e.g., hyperten- undergo periodic screening for the duration sion, renal failure, genitourinary cancer, or of their pregnancy. The IDSA makes no rec- decreased survival). For these reasons, the ommendations for subsequent screening of IDSA does not recommend screening for or treatment of asymptomatic bacteriuria in premenopausal nonpregnant women.2 TABLE 3 Oral Antibiotics for Treatment of Pregnant Women Pregnant Women with Asymptomatic Bacteriuria Women with asymptomatic bacteriuria dur- ing pregnancy are more likely to deliver pre- FDA Pregnancy Category B: Safety for use in pregnancy has not been established mature or low-birth-weight infants and have Amoxicillin a 20- to 30-fold increased risk of develop- Amoxicillin/clavulanate (Augmentin) ing during pregnancy com- Ampicillin pared with women without bacteriuria.16 Cefuroxime (Ceftin) A Cochrane systematic review found that Cephalexin (Keflex) studies have consistently reported that Nitrofurantoin (Furadantin) treatment of asymptomatic bacteriuria in pregnancy decreases the risk of subsequent Pregnancy Category C: No adequate well-controlled studies pyelonephritis from a range of 20 to 35 per- have been performed in women; should be used during pregnancy only if the potential benefit justifies the potential 17 cent to a range of 1 to 4 percent. Antimicro- risk to the fetus bial treatment of asymptomatic bacteriuria Ciprofloxacin (Cipro) also improves fetal outcomes, with decreases Gatifloxacin (Tequin) in the frequency of low-birth-weight infants Levofloxacin (Levaquin) 18,19 and preterm delivery. Early studies usu- Norfloxacin (Noroxin) ally continued antimicrobial therapy for the Trimethoprim/sulfamethoxazole (Bactrim, Septra) duration of pregnancy; however, more recent studies reported similar benefits in patients FDA = U.S. Food and Drug Administration. treated for 14 days with nitrofurantoin

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pregnant women found to have no asymp- Patients with Spinal Cord Injuries tomatic bacteriuria at the initial screen.2 Patients with spinal cord injuries have a higher prevalence of asymptomatic bacte- Women with Diabetes riuria and symptomatic UTI.6,34 Patients Studies of women with diabetes show no with spinal cord injuries and with asymp- difference between initially asymptomatic tomatic bacteriuria treated using antibiot- bacteriuric and nonbacteriuric women in the ics uniformly showed early recurrence of incidence of UTI, mortality, or progression bacteriuria following therapy. When treated to diabetic complications at 18 months25 or with seven to 14 days of antibiotics, 93 per- 14 years.26 In a study of antibiotic therapy cent of patients were again bacteriuric by versus no therapy for women with diabetes 30 days.35 Posttreatment urine cultures and asymptomatic bacteriuria, antimicro- showed increased antimicrobial resistance bial therapy did not delay or decrease the as well. A prospective, randomized trial in frequency of symptomatic UTI or the rate patients with asymptomatic bacteriuria and of hospitalization for UTI or other causes at intermittent catheterization showed similar up to three years’ follow-up.27 These studies rates of UTI at follow-up, whether or not pro- support the IDSA guidelines2 that screening phylactic antimicrobials were administered.36 for or treatment of asymptomatic bacteriuria Although there are few trials addressing the in women with diabetes is not indicated. treatment of asymptomatic bacteriuria in patients with spinal cord injuries, review Older Patients with Asymptomatic articles and consensus guidelines support the Bacteriuria IDSA recommendations2 that asymptomatic Studies of asymptomatic bacteriuria in pre- bacteriuria should not be screened for or and postmenopausal women report simi- treated in patients with spinal cord injuries. lar outcomes regardless of age.28,29 A study of ambulatory women in a long-term care Patients with Indwelling Urethral facility who were assigned to receive anti- Catheters microbial therapy or placebo for bacteriuria Patients with chronic indwelling Foley cath- showed a decrease in prevalence of asymp- eters are uniformly bacteriuric, but treatment tomatic bacteriuria at six months among is warranted only if the patient is symptom- those receiving antibiotics, but no signifi- atic. Urine that is cloudy or foul-smelling cant difference in symptomatic often prompts a call from a long-term care episodes.30 Adverse outcomes facility to the physician, with an expecta- Studies have consistently attributable to asymptomatic tion that an evaluation, if not antibiotic reported that treatment of bacteriuria were not observed therapy, will be ordered. However, in the asymptomatic bacteriuria in a cohort of ambulatory male asymptomatic patient, cloudy or foul smell- in pregnancy decreases the veterans older than 65 years at ing urine is not an indication for urinalysis, risk of subsequent pyelo- several years’ follow-up.10 culture, or antimicrobial treatment. A study nephritis from a range of Clinical trials of older resi- of residents in long-term care facilities with 20 to 35 percent to a range dents in long-term care facili- chronic indwelling catheters and bacteriuria of 1 to 4 percent. ties have shown no benefits who were treated with cephalexin (Keflex) from screening for or antimi- or no therapy showed no differences in the crobial treatment of asymptom- incidence of fever or reinfection; however, atic bacteriuria.31-33 Although antimicrobial patients who received antibiotic therapy had treatment does not decrease symptomatic twice the incidence of subsequent microbial infection or improve survival, there is an resistance to cephalexin.37 increased incidence of adverse antimicrobial When possible, the indwelling catheter effects and reinfection with antibiotic-resis- should be removed, and the patient should tant organisms. Thus, the IDSA does not receive clean intermittent catheterization recommend screening for or treatment of to reduce the risk of symptomatic UTI. The asymptomatic bacteriuria in older patients.2 replacement of a chronic indwelling Foley

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catheter is associated with a low risk for bac- REFERENCES teremia, and antimicrobial treatment or pro- 38 1. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer phylaxis is not indicated for this procedure. AJ, Stamm WE. Guidelines for antimicrobial therapy A study in young women with short-term of uncomplicated acute bacterial cystitis and acute catheterization reported increased symp- pyelonephritis in women. Infectious Diseases Society of tomatic infection over two weeks following America (IDSA). Clin Infect Dis 1999;29:745-58. 2. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, catheter removal, when asymptomatic bac- Hooton TM; Infectious Diseases Society of America; teriuria persisted 48 hours after the removal American Society of Nephrology; American Geriatric of the indwelling catheter.39 Accordingly, Society. Infectious Diseases Society of America guide- lines for the diagnosis and treatment of asymptomatic the IDSA recommends that asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54. bacteriuria should not be screened for or 3. Nicolle LE. Asymptomatic bacteriuria: when to treated in patients with an indwelling ure- screen and when to treat. Infect Dis Clin North Am thral catheter, but that treatment of women 2003;17:367-94 4. Zhanel GG, Harding GK, Nicolle LE. Asymptomatic bac- with persistent catheter-acquired bacteriuria teriuria in patients with diabetes mellitus. Rev Infect Dis at least 48 hours after catheter removal may 1991;13:150-4. be considered.2 5. Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am 1997;11:647-62. 6. Waites KB, Canupp KC, DeVivo MJ. Epidemiology and The Authors risk factors for following . Arch Phys Med Rehabil 1993;74:691-5. RICHARD COLGAN, M.D., is associate professor and direc- tor of undergraduate education of the Department of 7. Bakke A, Digranes A. Bacteriuria in patients treated with clean intermittent catheterization. Scand J Infect Family Medicine at the University of Maryland School of Dis 1991;23:577-82. Medicine, Baltimore. He received his medical degree from the Autonomous University of Guadalajara, Mexico, and 8. Chaudhry A, Stone WJ, Breyer JA. Occurrence of pyuria completed a residency in family medicine at the University and bacteriuria in asymptomatic hemodialysis patients. Am J Kidney Dis 1993;21:180-3. of Maryland School of Medicine. 9. Warren JW, Tenney JH, Hoopes JM, Muncie HL, Anthony LINDSAY E. NICOLLE, M.D., is a professor of internal WC. A prospective microbiologic study of bacteriuria in medicine and at the University of patients with chronic indwelling urethral catheters. Manitoba in Winnipeg, Canada, where she received her J Infect Dis 1982;146:719-23. medical degree. 10. Mims AD, Norman DC, Yamamura RH, Yoshikawa TT. Clinically inapparent (asymptomatic) bacteriuria ANDREW MCGLONE, M.D., currently is in private prac- in ambulatory elderly men: epidemiological, clini- tice in Annapolis, Md. While writing this article, he was cal, and microbiological findings. J Am Geriatr Soc chief resident in the Department of Family Medicine 1990;38:1209-14. at the University of Maryland School of Medicine. Dr. 11. Rubin RH, Shapiro ED, Andriole VT, Davis RJ, Stamm McGlone received his medical degree from the University WE. Evaluation of new anti-infective drugs for the of Maryland School of Medicine, where he also completed treatment of urinary tract infection. Infectious Diseases a residency in family medicine. Society of America and the Food and Drug Administra- tion. Clin Infect Dis 1992;15(suppl 1):S216-27. THOMAS M. HOOTON, M.D., currently is professor of 12. Lipsky BA, Ireton RC, Fihn SD, Hackett R, Berger RE. medicine and director of the Institute for Women’s Health Diagnosis of bacteriuria in men: specimen collection and at the University of Miami (Fla.) Miller School of Medicine. culture interpretation. J Infect Dis 1987;155:847-54. While writing this article, he was a professor of medicine in the Division of Allergy and Infectious Diseases at the 13. Saint S, Chenoweth CE. Biofilms and catheter-associ- ated urinary tract infections. Infect Dis Clin North Am University of Washington School of Medicine, Seattle, 2003;17:411-32. and medical director of the Harborview Medical Center HIV/AIDS Clinic in Seattle. Dr. Hooton received his medical 14. Sobel JD, Kaye D. Urinary tract infections. In: Mandell degree from the University of Texas Southwestern Medical GL, Douglas RG, Bennett JE, Dolin R. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious School, Dallas, and completed residencies in preven- Disease. 6th ed. Philadelphia, Pa.: Elsevier Churchill tive medicine at the Centers for Disease Control and Livingstone, 2005:906-26. Prevention, Atlanta, Ga., and in medicine at the University of Washington School of Medicine. 15. Hooton TM, Scholes D, Stapleton AE, Roberts PL, Win- ter C, Gupta K, et al. A prospective study of asymptom- Address correspondence to Richard Colgan, M.D., Dept. atic bacteriuria in sexually active young women. N Engl of Family Medicine, University of Maryland School J Med 2000;343:992-7. of Medicine, 29 South Paca St., Baltimore, MD 21201 16. Kincaid-Smith P, Bullen M. Bacteriuria in pregnancy. (e-mail: [email protected]). Reprints are not Lancet 1965;191:395-9. available from the authors. 17. Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001;(2): Author disclosure: Nothing to disclose. CD000490.

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18. Mittendorf R, Williams MA, Kass EH. Prevention of 29. Evans DA, Kass EH, Hennekens CH, Rosner B, Miao L, preterm delivery and low birth weight associated with Kendrick MI, et al. Bacteriuria and subsequent mortality asymptomatic bacteriuria. Clin Infect Dis 1992;14: in women. Lancet 1982;1:156-8. 927-32. 30. Boscia JA, Kobasa WD, Knight RA, Abrutyn E, Levi- 19. Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, son ME, Kaye D. Therapy vs no therapy for bacteri- Bracken M. Meta-analysis of the relationship between uria in elderly ambulatory non-hospitalized women. asymptomatic bacteriuria and preterm delivery/low JAMA1987;257:1067-71. birth weight. Obstet Gynecol 1989;73:576-82. 31. Nicolle LE, Mayhew WJ, Bryan L. Prospective random- 20. Whalley PJ, Cunningham FG. Short-term versus con- ized comparison of therapy and no therapy for asymp- tinuous antimicrobial therapy for asymptomatic bacte- tomatic bacteriuria in institutionalized elderly women. riuria in pregnancy. Obstet Gynecol 1977;49:262-5. Am J Med 1987;83:27-33. 21. Villar J, Widmer M, Lydon-Rochelle MT, Gulmezoglu 32. Abrutyn E, Mossey J, Berlin JA, Boscia J, Levison M, AM, Roganti A. Duration of treatment for asymptom- Pitsakis P, et al. Does asymptomatic bacteriuria predict atic bacteriuria during pregnancy. Cochrane Database mortality and does antimicrobial treatment reduce Syst Rev 2000;(2):CD000491. mortality in elderly ambulatory women [Published cor- 22. Bachman JW, Heise RH, Naessens JM, Timmerman MG. rection appears in Ann Intern Med 1994;121:901]? Ann A study of various tests to detect asymptomatic uri- Intern Med 1994;120:827-33. nary tract infections in an obstetric population. JAMA 33. Ouslander JG, Schapira M, Schnelle JF, Uman G, Fingold 1993;270:1971-4. S, Tuico E, et al. Does eradicating bacteriuria affect 23. Stenqvist K, Dahlen-Nilsson I, Lidin-Janson G, Lincoln the severity of chronic urinary incontinence in nursing K, Oden A, Rignell S, et al. Bacteriuria in pregnancy. home residents? Ann Intern Med 1995;122:749-54. Frequency and risk of acquisition. Am J Epidemiol 34. Erickson RP, Merritt JL, Opitz JL, Ilstrup DM. Bacteriuria 1989;129:372-9. during follow-up in patients with spinal cord injury: I. 24. Wadland WC, Plante DA. Screening for asymptomatic Rates of bacteriuria in various bladder-emptying meth- bacteriuria in pregnancy. A decision and cost analysis. ods. Arch Phys Med Rehabil 1982;63:409-12. J Fam Pract 1989;29:372-6. 35. Waites KB, Canupp KC, DeVivo MJ. Eradication of 25. Geerlings SE, Stolk RP, Camps MJ, Netten PM, Collet JT, urinary tract infection following spinal cord injury. Schneeberger PM, et al. Consequences of asymptom- Paraplegia 1993;31:645-52. atic bacteriuria in women with diabetes mellitus. Arch 36. Maynard FM, Diokno AC. Urinary infection and com- Intern Med 2001;161:1421-7. plications during clean intermittent catheterization 26. Semetkowska-Jurkiewicz E, Horoszek-Maziarz S, Galin- following spinal cord injury. J Urol 1984;132:943-6. ski J, Manitius A, Krupa-Wojciechowska B. The clinical 37. Warren JW, Anthony WC, Hoopes JM, Muncie HL Jr. course of untreated asymptomatic bacteriuria in dia- Cephalexin for susceptible bacteriuria in afebrile, long- betic patients–14-year follow-up. Mater Med Pol 1995; term catheterized patients. JAMA1982;248:454-8. 27:91-5. 38. Bregenzer T, Frei R, Widmer AF, Seiler W, Probst W, 27. Harding GK, Zhanel GG, Nicolle LE, Cheang M, for the Mattarelli G, et al. Low risk of bacteremia during cath- Manitoba Diabetes Urinary Tract Infection Study Group. eter replacement in patients with long-term urinary Antimicrobial treatment in diabetic women with asymp- catheters. Arch Intern Med 1997;157:521-5. tomatic bacteriuria. N Engl J Med 2002;347:1576-83. 39. Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, 28. Bengtsson C, Bengtsson U, Bjorkelund C, Lincoln K, Forward KR, Low DE, et al. How long should cath- Sigurdsson JA. Bacteriuria in a population sample of eter-acquired urinary tract infection in women be women: 24-year follow-up study. Results from the pro- treated? A randomized controlled study. Ann Intern spective population-based study of women in Gothen- Med 1991;114:713-9. burg, Sweden. Scand J Urol Nephrol 1998;32:284-9.

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