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Research Letters |

Intravesical Bacille Calmette-Guérin in Patients With Asymptomatic Bacteriuria FREE

Harry W. Herr, MD
JAMA. 2011;305(14):1413-1414. doi:10.1001/jama.2011.428.
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To the Editor: Asymptomatic bacteriuria is common in adults and does not require treatment.1 Practice guidelines, however, recommend antibiotics to sterilize the urine before urological procedures.2 Although intravesical bacille Calmette-Guérin (BCG) therapy for high-risk superficial bladder cancer is not specifically mentioned, urologists are reluctant to administer BCG to infected patients because of a possible risk of bacterial or BCG sepsis or an abrogated response to BCG.3 On the other hand, antibacterial treatment of asymptomatic bacteriuria leads to treatment delay and promotes antibiotic resistance. This study investigated whether intravesical BCG is safe and effective in bladder cancer patients with asymptomatic bacteriuria.

Two hundred consecutive patients with bladder cancer seen as outpatients in the urology department at Memorial Sloan-Kettering Cancer Center by 1 surgeon between January 1, 2009, and December 31, 2010, were eligible. All agreed to participate and provided oral informed consent. None was febrile or had symptoms of a urinary tract infection (UTI). On the first day of treatment, each patient submitted a clean-catch voided urine sample for bacteriologic studies. Patients then underwent instillations of BCG through a small urethral catheter once a week for 6 weeks and did not receive antibiotics. Patients were monitored each week during treatments and then weekly by telephone. Febrile UTI was defined as fever 102°F or greater and a positive urine culture. After the first culture, no further urine cultures were obtained unless prompted by fever and symptoms. At 3 months, patients were evaluated for response to BCG by cystoscopy and biopsy. The sample size was based on a projected proportion of at least 20% of patients with bacteriuria,1 and at least 5% developing a UTI, with no difference between infected and uninfected patients. χ2 test was used to test the correlation of bacteriuria with the frequency of UTI and response to BCG therapy, with a 2-sided significance level of .05. Data analyses were conducted using SPSS version 19 (SPSS Inc, Chicago, Illinois). The study was approved by the hospital's institutional review board.

The median age of the patients was 67 years (range, 36-93 years), and 148 (74%) were male. None of the patients had previous UTIs. All had received a single intravenous dose of a broad-spectrum antibiotic 2 to 4 weeks previously at the time of their transurethral tumor resection. None had an indwelling catheter or used self-catheterization. Sixteen patients had diabetes. None was taking immunosuppressive medications.

All 200 patients received 6 doses of BCG without receiving antibiotics, and all were evaluated at 3 months. Fifty-one patients (25%) had significant single-organism bacteriuria at baseline (Table). Only 1 (1.9%; 95% confidence interval, 0.86%-3.1%) developed a subsequent febrile UTI after completing induction BCG therapy. Another patient with sterile urine developed a UTI. The UTIs developed 1 week and 3 weeks, respectively, after the patients completed 6 weeks of induction BCG therapy. Both infections resolved with oral antibiotics. None of the patients was admitted for bacterial or BCG sepsis. UTI developed with equal frequency (P = .15) despite presence of bacteriuria, and there was no difference (P = .97) in the 3-month response to BCG between infected and uninfected patients (Table).

Table Graphic Jump LocationTable. Outcomes After Bacille Calmette-Guérin Therapy by Urine Culture Results

In this study, instillation of BCG into bladder cancer patients with asymptomatic bacteriuria did not result in sepsis or reduced response. The study is limited by a small number of patients treated by 1 surgeon in a single center. If the findings are replicated, screening urinalysis and culture to detect and treat bacteriuria in afebrile patients with bladder cancer may be unnecessary before starting weekly intravesical BCG therapy, as long as attention is paid to meticulous instillation technique and patients are closely monitored. Such a strategy would result in timely administration of BCG therapy and avoid overuse of antibiotics.4

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM.Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society.  Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults.  Clin Infect Dis. 2005;40(5):643-654
PubMed   |  Link to Article
Schaeffer EM. Prophylactic use of antimicrobials in commonly performed outpatient urologic procedures.  Nat Clin Pract Urol. 2006;3(1):24-31
PubMed   |  Link to Article
Billips BK, Forrestal SG, Rycyk MT, Johnson JR, Klumpp DJ, Schaeffer AJ. Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli Infect Immun. 2007;75(11):5353-5360
PubMed   |  Link to Article
Gross PA, Patel B. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria.  Clin Infect Dis. 2007;45(10):1335-1337
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Outcomes After Bacille Calmette-Guérin Therapy by Urine Culture Results

References

Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM.Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society.  Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults.  Clin Infect Dis. 2005;40(5):643-654
PubMed   |  Link to Article
Schaeffer EM. Prophylactic use of antimicrobials in commonly performed outpatient urologic procedures.  Nat Clin Pract Urol. 2006;3(1):24-31
PubMed   |  Link to Article
Billips BK, Forrestal SG, Rycyk MT, Johnson JR, Klumpp DJ, Schaeffer AJ. Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli Infect Immun. 2007;75(11):5353-5360
PubMed   |  Link to Article
Gross PA, Patel B. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria.  Clin Infect Dis. 2007;45(10):1335-1337
PubMed   |  Link to Article
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