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Editorial
 NEJM

Volume 347:1617-1618 November 14, 2002 Number 20

Asymptomatic Bacteriuria in Patients with Diabetes � Enemy or Innocent Visitor?

The application of quantitative bacteriology to urine cultures almost five decades ago led to prospective scientific investigations of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of urinary tract infections.1 Numerous studies have evaluated the frequency of asymptomatic and symptomatic bacteriuria in men and women with diabetes.2,3 The early studies showed no significant difference in the prevalence of bacteriuria between men with diabetes and men without diabetes. In contrast, the prevalence of asymptomatic bacteriuria is two to three times as high among women with diabetes as among women without diabetes, and the frequency of symptomatic urinary tract infections is higher among women with diabetes than among those without diabetes.2,3

Furthermore, localization studies have shown that infection of the upper urinary tract at initial testing is more common among women with bacteriuria and diabetes (occurring in 63 percent) than among women with bacteriuria but no diabetes (43 percent). Eighty percent of women with diabetes and bacteriuria have been shown to have renal parenchymal infection by seven weeks after initial testing.4,5 An autopsy series documented a frequency of acute pyelonephritis among patients with diabetes that was four to five times as high as that among patients without diabetes.6 The urinary tract is also a more common source of bacteremia among patients with diabetes.2,7 Finally, among women with diabetes, complicated symptomatic urinary tract infections are associated with higher frequencies of acute pyelonephritis, urosepsis, and bilateral renal infection and a higher risk of hospitalization than they are among nondiabetic women with symptomatic bacteriuria.2,8 Other serious, although less common, complications of symptomatic bacteriuria associated with diabetes include renal and perirenal abscesses, emphysematous cystitis, emphysematous pyelonephritis, renal papillary necrosis, fungal urinary tract infections � most frequently caused by candida species � and xanthogranulomatous pyelonephritis.

Symptomatic bacteriuria in patients with diabetes mellitus is serious and warrants proper clinical attention for both diagnosis and treatment. Clinicians understand these facts well. Because of the frequency of upper urinary tract infection, potential upper tract complications, and frequent recurrent infections, most investigators recommend cultures for all urinary tract infections in patients with diabetes, whereas we no longer recommend initial urine cultures for nondiabetic young women with uncomplicated cystitis. Follow-up urine culture after completion of antimicrobial therapy is also recommended for most women with diabetes in order to identify patients in whom bacteriologic cure has not been achieved.2

Why do patients with diabetes mellitus have an increased frequency of urinary tract infections, and why do they have more serious complications? Despite numerous studies, the exact pathogenesis of this problem has not been clearly defined.2 Although risk factors such as age, degree of glycosuria, and instrumentation have been suspected, studies have not confirmed that these factors are major contributors. A variety of factors may contribute, of which bladder dysfunction as a result of diabetic neuropathy and cystopathy may be the most important. Impaired sensation in the bladder results in bladder distention and increased residual volume, which results in a physiological obstruction of the urinary tract, which, in turn, increases the susceptibility to infection and allows infection to be initiated by much smaller numbers of uropathogens. There is also a higher prevalence of genitourinary structural abnormalities (cystocele, cystourethrocele, and rectocele) among women with diabetes who have recurrent urinary tract infections (30 percent) than among nondiabetic women with such infections (4 percent).2,9 Most agree that these factors and others contribute to the increased prevalence and severity of urinary tract infections in patients with diabetes.

What is the importance, if any, of asymptomatic bacteriuria in women with diabetes mellitus? Many investigators have recommended screening patients with diabetes to detect and then treat asymptomatic bacteriuria because of the increased frequency and severity of upper urinary tract infections associated with symptomatic bacteriuria in such patients, even though there are few data to support this recommendation. Many of us have considered asymptomatic bacteriuria in patients with diabetes to be "the enemy at the gate." So why not attempt to eliminate the enemy before serious harm is done to our patients? This approach is definitely useful in pregnant patients to reduce their increased risk of acute pyelonephritis and the accompanying risks of prematurity and low birth weight in their infants.10 This approach is also indicated in patients who are about to undergo urologic surgery, in order to reduce the risk of postoperative complications including bacteremia,11 and in recipients of renal transplants soon after transplantation. Since treatment of asymptomatic bacteriuria in these three groups of patients has been so successful, we suspected that it would also be effective in patients with diabetes mellitus and asymptomatic bacteriuria.

In this issue of the Journal, Harding et al.12 describe a detailed study of the effect of antimicrobial therapy on asymptomatic bacteriuria in women with diabetes mellitus. The study was a prospective, randomized trial comparing antimicrobial therapy with no antimicrobial therapy in women with diabetes and asymptomatic bacteriuria who were then followed for 36 months. For the first 6 weeks, the study was double-blinded and placebo-controlled, so that patients received either 14 days of antimicrobial treatment or placebo. Furthermore, patients were monitored meticulously, and there are data on duration and complications of diabetes, medications, ethnic background, sexual activity, previous urinary tract infections, genitourinary surgery, reproductive history, urinary symptoms, and quantitative urine cultures including sensitivity testing, urinalysis, and measurement of blood sugars, glycosylated hemoglobin, renal function, and urinary protein and glucose. All factors were analyzed statistically, and the results are unequivocal.

As compared with placebo, antimicrobial therapy effectively reduced the incidence of asymptomatic bacteriuria in treated women as assessed four weeks after therapy. However, the antimicrobial therapy did not alter the incidence of symptomatic bacteriuria (cystitis, pyelonephritis, and hospitalization) during the ensuing 27 months of follow-up, although there was a slight but nonsignificant trend in favor of the antimicrobial treatment. Treatment also did not alter the time to the first symptomatic episode of urinary tract infection. Most subjects in both treatment groups had no symptomatic episodes during the follow-up period. The treated patients did have significantly more new episodes of asymptomatic bacteriuria, and they had more adverse events from antimicrobial therapy for urinary tract infections. The metabolic status and diabetic complications (renal function, degree of proteinuria, and glycosylated hemoglobin level) remained similar in the treated and untreated groups. There was no association of symptomatic episodes with previous genitourinary surgery, ethnic background, type or duration of diabetes, presence or absence of retinopathy or nephropathy, blood glucose level, or presence or absence of pyuria, glycosuria, or proteinuria. Thus, the results of this complex but excellent study strongly suggest that there are no substantial benefits from screening women with diabetes mellitus for asymptomatic bacteriuria or from treating it. Although treatment resulted in the short-term clearance of bacteriuria, it failed to prevent symptomatic episodes and hospitalizations or even to delay the onset of symptomatic infections. These observations are consistent with earlier observations showing that treatment of asymptomatic bacteriuria was not beneficial in schoolgirls, patients with spinal cord injuries, or institutionalized elderly men and women.

The study by Harding and colleagues should lead to a change in our delivery of health care to women with diabetes mellitus. Resources now spent on screening and treatment in such patients should instead be used to identify the precursors that do lead to symptomatic urinary tract infections in patients with diabetes. Asymptomatic bacteriuria in women with diabetes mellitus may just be an innocent visitor; even if it is an enemy, a few weeks of antimicrobial therapy for asymptomatic infection is not beneficial. But we must fight back promptly and effectively when the enemy reveals itself and threatens the well-being of women with diabetes.


Vincent T. Andriole, M.D.
Yale University School of Medicine
New Haven, CT 06520

References

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  2. Patterson JE, Andriole VT. Bacterial urinary tract infections in diabetes. Infect Dis Clin North Am 1997;11:735-750. [ISI][Medline]
  3. Zhanel GG, Nicolle LE, Harding GKM, Manitoba Diabetic Urinary Infection Study Group. Prevalence of asymptomatic bacteriuria and associated host factors in women with diabetes mellitus. Clin Infect Dis 1995;21:316-322. [ISI][Medline]
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  8. Nicolle LE, Friesen D, Harding GKM, Roos LL. Hospitalization for acute pyelonephritis in Manitoba, Canada, during the period from 1989 to 1992: impact of diabetes, pregnancy, and aboriginal origin. Clin Infect Dis 1996;22:1051-1056. [ISI][Medline]
  9. Forland M, Thomas VL. The treatment of urinary tract infections in women with diabetes mellitus. Diabetes Care 1985;8:499-506. [Abstract]
  10. Patterson TF, Andriole VT. Detection, significance, and therapy of bacteriuria in pregnancy: update in the managed health care area. Infect Dis Clin North Am 1997;11:593-608. [ISI][Medline]
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  12. Harding GKM, Zhanel GG, Nicolle LE, Cheang M. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med 2002;347:1576-1583. [Abstract/Full Text]