Reappraisal of Single-Dose Antibiotic Treatment for Uncomplicated Urinary Tract Infection in Adult Women: A Systematic Review and Network Meta-Analysis of 58 Randomized Clinical Trials

Abstract

Background: This systematic review and network meta-analysis of randomized clinical trials (RCTs) was conducted to reappraise the efficacies of various antibiotic regimens for the treatment of uncomplicated urinary tract infection (UTI), with a particular focus on single-dose therapies. Methods: The PubMed/Medline, Embase, and Cochrane Library databases were searched for relevant publications up to April 2018. Subsequently, the identified trials were evaluated for eligibility using the PICOS (participants, interventions, comparators, outcomes, and study design) approach according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Moreover, the efficacies of each antibiotic treatment regimen in terms of clinical and microbial responses were directly and indirectly compared. Findings: This analysis included 58 prospective RCTs (19,527 patients) with at least two arms that compared the efficacies of several antibiotic regimens, including placebo effect, in female patients with uncomplicated UTI. Notably, all antibiotic therapy regimens except amoxicillin single-dose and nitrofurantoin 3-days were significantly more effective than placebo with respect to clinical responses, while all except 1st-generation cephalosporin single-dose and nitrofurantoin 3-day treatments were more effective in terms of microbial responses. Notably, 2nd-, 3rd-, and 4th-generation fluoroquinolone; fosfomycin trometamol; trimethoprim-sulfamethoxazole; 3rd-generation cephalosporin; and amoxicillin/clavulanic acid single-dose therapies yielded more effective clinical and microbial responses, compared to placebo. Interpretation: Our meta-analysis showed that most single-dose therapies were not inferior to longer-duration antibiotic regimens. Although appropriate antibiotics for uncomplicated UTI should be determined based on preceding studies of local drug resistance, the potential benefits and uses of single-dose therapy should be reconsidered. Funding Statement: This study was supported by a faculty research grant from the Yonsei University College of Medicine (6-2018-0043). Declaration of Interests: The authors have nothing to disclose. Ethics Approval Statement: The authors used the PRISMA framework to analyze and summarize our systematic analysis and meta-review process. This systematic review was registered in PROSPERO (CRD42018093529).