Antibiotic class comparisons for the treatment of pyelonephritis and complicated urinary tract infections: a systematic review and meta-analysis
Abstract
BACKGROUND
The relative efficacy of antibiotic classes for pyelonephritis and complicated UTI (cUTI) remains unclear, as different antibiotic classes vary in antimicrobial activity, pharmacodynamics, and pharmacokinetics.
METHODS
Systematic review and meta-analysis. We searched PubMed, Cochrane CENTRAL, clinical-trial registries, and conference abstracts through 30 November 2025. Randomized controlled trials comparing antibiotic classes in adults with pyelonephritis/ cUTI were eligible (PROSPERO CRD42023448020). Five comparisons were analyzed: quinolones vs β-lactams, cephalosporins vs penicillins, aminoglycosides vs quinolones or beta-lactams, trimethoprim-sulfamethoxazole vs quinolones or beta-lactams, and ESBL-active agents vs non-ESBL-active antibiotics. The primary outcome was clinical cure by day 7. We compiled risk ratios (RRs) with 95% confidence intervals (CI) using fixed-effect meta-analyses. Risk of bias was assessed with ROB 2.0 and evidence certainty using GRADE.
RESULTS
Thirty-seven RCTs were included, comprising 7,904 mainly hospitalized participants (62.7% women). Most had some risk-of-bias concerns. No significant difference in clinical cure was observed with moderate evidence certainty, across all comparisons. Relapse increased significantly with TMP/ SMX compared to quinolones or beta-lactams (RR 2.34 [1.29, 4.24]) and microbiological cure improved with ESBL-active antibiotics (RR 1.07 [1.02, 1.13], very low certainty evidence). TMP/ SMX increased adverse…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,904 participants or records.
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