Comparative effectiveness of oral antibiotics to treat uncomplicated urinary tract infections in male outpatients
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: New IDSA guidelines define uncomplicated UTI (uUTI) as infection limited to the bladder in both men and women. This study compared the effectiveness of β-lactams, nitrofurantoin and trimethoprim/sulfamethoxazole (TMP/SMX) to fluoroquinolones for outpatient uUTI treatment in men. Materials & methods: A retrospective cohort of adult male outpatients diagnosed with uUTI during 2019–2021 in the Department of Veterans Affairs system was created. Inclusion required an Emergency Department, Urgent/Primary Care visit with ICD-10 documentation of UTI and a prescription of interest dispensed. Patients with recent UTI, hospitalization, infectious co-diagnosis, temperature >99.9 F, pyelonephritis or prostatitis, or for whom asymptomatic bacteriuria treatment was appropriate were excluded. Overlap weighting propensity scores and generalized estimating equation models assessed the relative risk of a subsequent UTI-related visit or hospitalization within 3–30 days with a new antibiotic dispensed. Results: A total of 45,442 males (mean [SD]) age 71.6 (12.7) years were treated at 130 VA medical centers. Treatment n (%) included: β-lactams 17,655 (38.9%), nitrofurantoin 8394 (18.5%), TMP/SMX 9709 (21.4%) and fluoroquinolones 9684 (21.3%). UTI-related return visits occurred in 5453 (12.0%) and UTI-related hospitalization occurred in 1431 (3.1%). The adjusted relative risk (aRR, [95% CI]) of a return visit compared with fluoroquinolones was higher for β-lactams (1.22, [1.02, 1.48]) and nitrofurantoin (1.47, [1.23, 1.74]) but not for TMP/SMX (0.99, [0.80, 1.23]). The aRR for UTI-related hospitalization was not different for β-lactams (1.06, [0.80, 1.40] or TMP/SMX [0.80, [0.56, 1.15], but was lower for nitrofurantoin [0.60, [0.41, 0.89]). Conclusion: Compared with fluoroquinolones, β-lactam and nitrofurantoin prescribed for outpatient uUTI were associated with modestly increased UTI-related return visits but not hospitalization in men.
Plain language summary
Historically, urinary tract infection (UTI) in men have been considered to be complicated and to require prolonged treatment with antibiotics that achieve high systemic concentrations. New treatment guidelines classify infection limited to the bladder as uncomplicated (uUTI) in men which can be treated with shortened courses of select antibiotics. This study compared the effectiveness of commonly prescribed antibiotics for outpatient uUTI in men. A retrospective cohort of outpatients diagnosed with uUTI in the U.S. Department of Veterans Affairs system was conducted. Propensity score methods and generalized estimating equation models assessed the relative risk for subsequent UTI-related visit or hospitalization. The findings indicate that the commonly prescribed oral antibiotics nitrofurantoin, aminopencillins, and cephalosporins, but not trimethoprim/sulfamethoxazole were associated with a higher UTI return visit rate than fluoroquinolones and that shortened course treatment was not associated with a worse outcome. These findings generally support the new guideline recommendations for antibiotic selection and treatment duration in men.
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References
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Received: 9 October 2025
Accepted: 13 February 2026
Published online: 26 March 2026
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Comparative effectiveness of oral antibiotics to treat uncomplicated urinary tract infections in male outpatients. (2026) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2025-0163
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