Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness.
Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men.
Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized.
Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment.
Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication.
Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group.
Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI.
Trial Registration: ClinicalTrials.gov identifier: NCT01994538.
|Original language||English (US)|
|Number of pages||8|
|Journal||JAMA - Journal of the American Medical Association|
|State||Published - Jul 27 2021|
Bibliographical noteFunding Information:
reports research and consulting funding from Genentech and the National Institute of Allergy and Infectious Diseases for COVID trials; consultancy fees from Genentech; and grants from the US Department of Veterans Affairs (VA) Rehabilitation Research & Development Service and the Agency for Healthcare Research and Quality. Ms Amundson reports receiving salary support for this trial during the conduct of the study from VA Merit Review grants. Dr. Johnson reports grant support from Allergan/Actavis, Cipla/Achaogen, Melinta, Merck, Shionogi, Synitron, Tetraphase; consulting fees from Crucell/Janssen; and pending patents for 2 E coli strain tests. No other conflicts were reported.
Funding/Support: The study was funded by the VA Merit Review Program, grant number I01BX007080. Dr Trautner’s work is supported in part by a grant from the Houston VA Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety (CIN 13-413).
© 2021 American Medical Association. All rights reserved.
- Anti-Bacterial Agents/administration & dosage
- Ciprofloxacin/administration & dosage
- Double-Blind Method
- Drug Administration Schedule
- Duration of Therapy
- Middle Aged
- Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
- Urinary Tract Infections/drug therapy
PubMed: MeSH publication types
- Equivalence Trial
- Research Support, Non-U.S. Gov't
- Randomized Controlled Trial
- Multicenter Study
- Pragmatic Clinical Trial
- Journal Article
- Comparative Study