Comparative effectiveness of oral antibiotics to treat uncomplicated urinary tract infections in male outpatients

<b>Aim:</b> 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. <b>Materials & methods:</b> 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. <b>Results:</b> 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]). <b>Conclusion:</b> 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.