Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial.

CONTEXT: Although fluoroquinolones remain the most reliable urinary antimicrobial, resistance rates have increased and effective fluoroquinolone-sparing antimicrobials are needed. OBJECTIVE: To determine whether cefpodoxime is noninferior to ciprofloxacin for treatment of acute cystitis. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial of 300 women aged 18 to 55 years with acute uncomplicated cystitis comparing ciprofloxacin (n = 150) with cefpodoxime (n = 150); patients were from a student health center in Seattle, Washington, and a referral center in Miami, Florida. The study was conducted from 2005 to 2009 and outcomes were assessed at 5 to 9 days and 28 to 30 days after completion of therapy. Intent-to-treat and per-protocol analyses were performed; 15 women in the ciprofloxacin group and 17 women in the cefpodoxime group were lost to follow-up. INTERVENTIONS: Patients were given 250 mg of ciprofloxacin orally twice daily for 3 days or 100 mg of cefpodoxime proxetil orally twice daily for 3 days. MAIN OUTCOME MEASURES: Overall clinical cure (defined as not requiring antimicrobial treatment during follow-up) at the 30-day follow-up visit. Secondary outcomes were clinical and microbiological cure at the first follow-up visit and vaginal Escherichia coli colonization at each follow-up visit. The hypothesis that cefpodoxime would be noninferior to ciprofloxacin by a 10% margin (ie, for the difference in the primary outcome for ciprofloxacin minus cefpodoxime, the upper limit of the confidence interval would be <10%) was formulated prior to data collection. RESULTS: The overall clinical cure rate at the 30-day visit with the intent-to-treat approach in which patients lost to follow-up were considered as having clinical cure was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%); and for the intent-to-treat approach in which patients lost to follow-up were considered as having not responded to treatment, the clinical cure rate was 83% (124/150) for ciprofloxacin compared with 71% (106/150) for cefpodoxime (difference of 12%; 95% CI, 3%-21%). The microbiological cure rate was 96% (123/128) for ciprofloxacin compared with 81% (104/129) for cefpodoxime (difference of 15%; 95% CI, 8%-23%). At first follow-up, 16% of women in the ciprofloxacin group compared with 40% of women in the cefpodoxime group had vaginal E coli colonization. CONCLUSIONS: Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for noninferiority for achieving clinical cure. These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum ß-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00194532.

Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women.

BACKGROUND: There is a paucity of data on the efficacy of nitrofurantoin for the treatment of acute uncomplicated cystitis in regimens shorter than 7 days. Evidence-based use of this drug is increasingly important as trimethoprim-sulfamethoxazole resistance among uropathogens increases. METHODS: To assess the efficacy of nitrofurantoin vs trimethoprim-sulfamethoxazole, 338 women aged 18 to 45 years with acute uncomplicated cystitis were randomized to open-label treatment with either trimethoprim-sulfamethoxazole, 1 double-strength tablet twice daily for 3 days, or nitrofurantoin, 100 mg twice daily for 5 days. Clinical cure 30 days after therapy was the main outcome measure. Secondary outcomes included clinical and microbiological cure rates 5 to 9 days after therapy and, for trimethoprim-sulfamethoxazole-treated women, clinical cure stratified by the trimethoprim-sulfamethoxazole susceptibility of the uropathogen. RESULTS: Clinical cure was achieved in 79% of the trimethoprim-sulfamethoxazole group and in 84% of the nitrofurantoin group, for a difference of -5% (95% confidence interval, -13% to 4%). Clinical and microbiological cure rates at the first follow-up visit were also equivalent between the 2 groups. In the trimethoprim-sulfamethoxazole arm, 7 of 17 women (41%) with a trimethoprim-sulfamethoxazole-nonsusceptible isolate had a clinical cure compared with 84% of women with a trimethoprim-sulfamethoxazole-susceptible isolate (P < .001). CONCLUSION: A 5-day course of nitrofurantoin is equivalent clinically and microbiologically to a 3-day course of trimethoprim-sulfamethoxazole and should be considered an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women.

Isolation of fluoroquinolone-resistant rectal Escherichia coli after treatment of acute uncomplicated cystitis.

OBJECTIVES: Given increasing rates of co-trimoxazole resistance among uropathogens causing acute uncomplicated cystitis, fluoroquinolones, nitrofurantoin and fosfomycin are often considered as alternative empirical therapy. The choice between these drugs should depend in part on whether they are associated with the isolation of drug-resistant microbial flora. We conducted a randomized treatment trial to assess the effects of ciprofloxacin, nitrofurantoin and fosfomycin on the rectal microbial flora of women with acute uncomplicated cystitis, including isolation of fluoroquinolone-resistant strains. METHODS: Pre-menopausal women presenting with acute uncomplicated cystitis were randomized to treatment with 3 days of ciprofloxacin, 7 days of nitrofurantoin, or a single dose of fosfomycin. Women were followed for 1 month for evaluation of clinical and microbiological responses as well as for isolation of resistant rectal E. coli. RESULTS: Sixty-two women (25 ciprofloxacin, 17 nitrofurantoin, 20 fosfomycin) were enrolled and eligible for analysis. All three regimens were well tolerated and resulted in >90% clinical and bacteriological cure. The prevalence of rectal E. coli was markedly decreased by ciprofloxacin and fosfomycin, but not by nitrofurantoin. One woman treated with ciprofloxacin had emergence of two ciprofloxacin-resistant rectal E. coli strains within 10 days of completing therapy. No emergence of resistance was observed in the other two treatment groups. CONCLUSIONS: This study demonstrates that fluoroquinolone-resistant E. coli remain infrequent in the rectal flora of women with uncomplicated cystitis in Seattle. However, a 3 day course of a fluoroquinolone for treatment of uncomplicated cystitis was followed by isolation of fluoroquinolone-resistant rectal E. coli in one patient.

Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial.

CONTEXT: The high prevalence of resistance to trimethoprim-sulfamethoxazole and other antimicrobials among Escherichia coli causing acute cystitis in women has led to increased use of alternative antibiotics. One such antibiotic, amoxicillin-clavulanate, has not been well studied. OBJECTIVE: To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate to that of a 3-day regimen of ciprofloxacin in the treatment of acute cystitis in women. The primary study hypothesis was that the amoxicillin-clavulanate and ciprofloxacin treatment groups would differ in clinical cure. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind treatment trial of 370 women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis and a urine culture with at least 10(2) colony-forming units of uropathogens per milliliter from a university student health center or a health maintenance organization. INTERVENTIONS: Women were randomly assigned to receive amoxicillin-clavulanate (500 mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for 3 days and were followed up for 4 months. MAIN OUTCOME MEASURES: The main outcome measure was clinical cure. Secondary study outcomes of interest were microbiological cure and vaginal E coli colonization at the 2-week follow-up visit. RESULTS: Clinical cure was observed in 93 (58%) of 160 women treated with amoxicillin-clavulanate compared with 124 (77%) of 162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate was not as effective as ciprofloxacin even among women infected with strains susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin-clavulanate group vs 114 [77%] of 149 women in the ciprofloxacin group; P = .004). The difference in clinical cure rates occurred almost entirely within the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared with 153 (95%) of 161 women treated with ciprofloxacin (P<.001). At this visit, 45% of women in the amoxicillin-clavulanate group compared with 10% in the ciprofloxacin group had vaginal colonization with E coli (P<.001). CONCLUSIONS: A 3-day regimen of amoxicillin-clavulanate is not as effective as ciprofloxacin for the treatment of acute uncomplicated cystitis, even in women infected with susceptible strains. This difference may be due to the inferior ability of amoxicillin-clavulanate to eradicate vaginal E coli, facilitating early reinfection.

Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.