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Oral β‐Lactams for Complicated Urinary Tract Infections: A Systematic Review and Point‐Counterpoint Comparison With Trimethoprim/Sulfamethoxazole and Fluoroquinolones

Ashlan J. Kunz Coyne, Jeannette L. Bouchard, Spencer H. Durham, Amy Y. Kang, Kinsey M. Johannemann, W Justin Moore, Kevin Nguyen, James M. Sanders et al.

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy, 2026

3 citations

Abstract

BACKGROUND: Rising resistance and toxicity concerns with fluoroquinolones (FQs) and trimethoprim/sulfamethoxazole (TMP/SMX) have prompted interest in oral β-lactams as alternatives for complicated urinary tract infections (cUTIs). This review evaluates the effectiveness, safety, and pharmacokinetic (PK) considerations of oral β-lactams compared to FQs and TMP/SMX in these clinical contexts. A structured point-counterpoint discussion explores their role in antimicrobial stewardship and patient-centered therapy. METHODS: A systematic PubMed search identified studies published between January 2000 and December 2025. Eligible studies included randomized trials and observational cohort studies evaluating clinical effectiveness, microbiological outcomes, or safety of oral β-lactams for cUTIs or bacteremic UTI compared with FQs or TMP/SMX. Outcomes of interest included treatment success, recurrence, adverse events, and PK considerations. Excluded studies involved special populations, nontraditional agents, or infections outside the scope of cUTI. Data were synthesized narratively due to heterogeneity in study design and outcome reporting. RESULTS: Seventeen observational studies met the inclusion criteria. Oral β-lactams demonstrated comparable effectiveness to FQs and TMP/SMX for cUTIs, including bacteremic UTI, when dosed appropriately. Oral β-lactams with high oral bioavailability (e.g., cephalexin, cefpodoxime, cefuroxime, amoxicillin/clavulanate), showed success rates…

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