A Systematic Review and Network Meta-analysis of Empirical Antibiotics for Complicated Urinary Tract Infections

BACKGROUND: Empiric antibiotic selection for complicated urinary tract infections (cUTIs) is increasingly complex due to the rising prevalence of multidrug-resistant organisms. We conducted a network meta-analysis (NMA) to compare clinical efficacy and safety among existing empiric treatment options. METHODS: We performed a frequentist random-effects NMA of randomized controlled trials evaluating single-agent empiric regimens for adults with cUTIs. The primary endpoints were clinical response (CR), microbiological response, and serious adverse events (AEs). Ceftriaxone served as the common comparator. RESULTS: Forty-seven trials were identified through a systematic search. In the primary analysis of 17 studies published after the year 2000, evaluating agents currently accessible in the United States, in which baseline ceftriaxone non-susceptibility among Enterobacterales averaged approximately 15%. Ceftriaxone demonstrated CR rates comparable to broader-spectrum alternatives. Although some agents achieved higher microbiological eradication, these differences did not translate into superior clinical cure rates. Safety profiles were stable across antibiotic classes, with no significant differences in serious AEs compared to cephalosporins. CONCLUSIONS: Ceftriaxone remains an effective empiric option for hemodynamically stable adults with cUTIs in settings with comparable resistance prevalence. These findings provide evidence to support antimicrobial stewardship efforts that prioritize narrower-spectrum agents, preserving broader-spectrum therapies for patients at highest risk for resistant pathogens.