The Journal of Informed Pharmacotherapy 2000;1:210-212.
Download a PDF version of this article
Reviewer: Peter J. Zed, B.Sc., B.Sc. (Pharm), Pharm.D.
Reviewer's email address: email@example.com
Reviewer's profession/specialty: Pharmacy/Emergency Medicine
Talan DA, Stamm WE, Hooton TM, Moran GJ, Burke T, Iravani A, Reuning-Scherer J, Church DA. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women. A randomized trial. JAMA 2000;283:1583-90. PubMed Citation
This study was a prospective, multicentre, randomized, double-blind trial designed to compare the safety, efficacy and relative costs of oral ciprofloxacin for 7 days or oral trimethoprim-sulfamethoxazole for 14 days in women with acute uncomplicated pyelonephritis. Premenopausal women at least 18 years of age with a clinical diagnosis of acute uncomplicated pyelonephritis were enrolled in 25 outpatient centers. Eligible patients had flank pain and/or costovertebral angle tenderness; a temperature higher than 38.0C orally, or higher than 38.6C rectally; and pyuria. The primary study endpoints were continued bacteriologic and clinical cure through the 4-11 day posttherapy visit. Secondary endpoints included bacteriologic and clinical responses through the 22-48 day posttherapy visit. Adverse drug events, and health resource use and cost-per-cure analysis from the perspective of the third-party payer were also completed for all enrolled patients.
1. Was assignment of patients randomized?
Yes. Initial stratification to decide whether an initial dose of antimicrobial would be given intravenously or orally was made by the treating physician. Patients receiving an initial intravenous dose were administered 400 mg (IV) of ciprofloxacin or 1 g (IV) of ceftriaxone. Eligible patients were then randomly assigned to receive ciprofloxacin 500 mg or trimethoprim- sulfamethoxazole 160/800 mg tablets (PO) twice daily for 14 days. Ciprofloxacin-treated patients received placebo (PO) twice daily for the final 7 days.
1. How large was the treatment effect?
The primary endpoint of bacteriological cure at 4-11 days posttherapy for efficacy-valid patients was achieved in 99% of ciprofloxacin-treated patients compared to 89% for those treated with trimethoprim-sulfamethoxazole, absolute risk reduction (ARR) 10%, number needed to treat (NNT) 10; (95% confidence interval [CI] 0.04-0.16, p=0.004). Clinical cure at 4-11 days posttherapy was achieved in 96% of ciprofloxacin-treated patients compared to 83% for those treated with trimethoprim- sulfamethoxazole, ARR 13%, NNT 8; (95% CI 0.06-0.22, p=0.002). These results did not change when evaluated using intention-to-treat analysis for both bacteriologic and clinical cure. Bacteriological cure at the 22-48 days posttherapy was achieved in 85% of ciprofloxacin-treated patients compared to 74% for those treated with trimethoprim- sulfamethoxazole (95% CI 0.00-0.21, p=0.08). Clinical cure at 22-48 days posttherapy was achieved in 91% of ciprofloxacin-treated patients compared to 77% for those treated with trimethoprim-sulfamethoxazole, ARR 14%, NNT 8; (95% CI 0.03-0.23, p=0.02).
Forty-seven (18.4%) of all uropathogens (44 E. coli, 2. E. aerogenes and 1 P. mirabilis) were resistant to trimethoprim-sulfamethoxazole, while only one strain (P. mirabilis) was resistant to ciprofloxacin (0.4%, p<0.001). Among trimethoprim-sulfamethoxazole treated patients bacteriological and clinical cure was 50% (7 of 14) and 35% (6 of 17), respectively, as compared to 96% (73 of 76) and 92% (76 of 83) success rates for infections involving susceptible strains.
Adverse effects occurred in 33% of trimethoprim-sulfamethoxazole treated patients compared to 24% for those treated with ciprofloxacin resulting in study discontinuation in 11% and 6%, respectively. Gastrointestinal events (16% vs. 9%), headache (10% vs. 5%) and rash (7% vs. 2%) occurred more frequently in the trimethoprim-sulfamethoxazole group.
Health care resources for hospital stay, return medical visits or telephone consultation, laboratory tests including cultures were all higher in the trimethoprim-sulfamethoxazole-treated patients. The mean total cost per patient was $687 (US) for the trimethoprim-sulfamethoxazole group and $531 (US) for the ciprofloxacin group, a difference of $156 (US) (95% CI -$118-$443 (US)). The mean cost per cure was also higher in the trimethoprim-sulfamethoxazole group as compared to ciprofloxacin at $770 (US) and $615 (US), a difference of $155 (95% CI $102-$207 (US)).
2. How precise was the estimate of the treatment effect?
The 95% CI for the primary endpoint of continued bacteriologic and clinical cure at days 4-11 did not cross zero indicating statistical significance.
2. Were all clinically important outcomes considered?
Copyright © 2000 by the Journal of Informed Pharmacotherapy. All rights reserved.