A Meta-analysis of Randomized, Controlled Trials Comparing Short- and Long-Course Antibiotic Therapy for Urinary Tract Infections in Children

Abstract

Background. Short-course antibiotic regimens, ranging in duration from a single dose to 3 days, are the current standard of care for the treatment of acute lower urinary tract infections (UTIs) in adult women. Despite multiple small randomized, controlled trials (RCTs) showing no difference in efficacy between short-course (≤3 days) and long-course (7–14 days) therapy in children, concerns about occult pyelonephritis and renal scarring have prompted standard recommendations of 7 to 14 days of antibiotics for UTIs in children. Objective. To determine whether long-course antibiotic therapy is more effective than short-course therapy for the treatment of UTIs in children, and to explore potential sources of heterogeneity in the results of existing studies. Methods. We searched online bibliographic databases (Medline and Cochrane Clinical Trials Registry) for RCTs comparing short- and long-course therapy for the treatment of UTI in children, and examined the references of all retrieved articles. Candidate studies for meta-analysis were restricted to RCTs comparing short-course (≤3 days) and long-course (7–14 days) outpatient therapy for acute UTI in children age 0 to 18 years. We excluded studies that were restricted to children with recurrent UTI or included children with asymptomatic bacteriuria. Sixteen studies met the inclusion criteria. Study quality was evaluated using a 9-item scoring system developed by the investigators. Data on the primary outcomes—treatment failure and reinfection rate—were extracted when available and reanalyzed based on intention to treat whenever possible. To determine whether anatomic level of infection (upper vs lower urinary tract) influenced the results, the meta-analysis was repeated on the subgroup of studies that attempted to restrict their participants to children with lower UTI. To determine whether there was a dose-response effect for the duration of short-course therapy, we performed separate subgroup analyses of studies of single-dose or single-day therapy and studies of 3-day therapy. To explore other potential sources of study result heterogeneity, such as study quality and patient age, we developed a random-effects regression model that included these variables as covariates. Results. The pooled estimate for the relative risk (RR) of treatment failure with short-course antibiotic therapy was 1.94 (95% confidence interval [CI]: 1.19–3.15) and for the RR of reinfection was 0.76 (95% CI: 0.39–1.47). When we excluded the 3 studies that did not attempt to restrict their participants to patients with lower UTI, the pooled RR of treatment failure was 1.74 (95% CI: 1.05–2.88) and of reinfection was 0.69 (95% CI: 0.32–1.52). For the subgroup of studies comparing single-dose or 1-day therapy to long-course therapy, the pooled RR of treatment failure was 2.73 (95% CI: 1.38–5.40) and of reinfection was 0.37 (95% CI: 0.12–1.18). For the subgroup of studies comparing 3-day therapy to long-course therapy, the pooled RR of treatment failure was 1.36 (95% CI: 0.68–2.72) and of reinfection was 0.99 (95% CI: 0.46–2.13). In the meta-regression, neither study quality nor mean participant age was significantly associated with the odds ratio of treatment failure or reinfection, in either the complete set of studies or the subset of studies restricted to patients with lower UTI. Conclusions. In pooled analyses of published studies comparing long- and short-course antibiotic treatment of UTI in children, long-course therapy was associated with fewer treatment failures without a concomitant increase in reinfections, even when studies including patients with evidence of pyelonephritis were excluded from the analysis. Until there are more accurate methods for distinguishing upper from lower UTI in children, no additional comparative trials are warranted and clinicians should continue to treat children with UTI for 7 to 14 days.