Real-World Outcomes With Multidose Fosfomycin Compared to Nitrofurantoin for Lower Urinary Tract Infections Due to Extended-Spectrum β-Lactamase–Producing Enterobacterales

Background Nitrofurantoin and fosfomycin are recommended oral options for patients with lower urinary tract infections (UTI) due to extended-spectrum β-lactamase-–producing Enterobacterales (ESBL-E). Most studies that are available compare nitrofurantoin courses with a single dose of fosfomycin. Methods This was a retrospective study of noncritically ill adults hospitalized between January 2013 to October 2021, who were treated with multidose fosfomycin or nitrofurantoin for an ESBL-E UTI. We evaluated a composite primary outcome of clinical response combined with the absence of a recurrent UTI with the same pathogen in the 30 days after treatment. Results Out of 211 patients screened, 167 were included (fosfomycin n = 95; nitrofurantoin n = 72). A median of 3 doses of fosfomycin were used, while median duration of nitrofurantoin was 8 days. Patients treated with fosfomycin had a higher Charlson Comorbidity Index and more systemic signs of infection. The primary composite outcome was encountered in 91.6% (87/95) in the fosfomycin group and 83.3% (60/72) in the nitrofurantoin group, which met the predetermined noninferiority margin of 10%. Multivariate analysis identified absence of systemic involvement (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.109–9.091, P = 0.031), days on initial lead-in antibiotics (OR 1.4, 95% CI 1.034–1.912, P = 0.030), and duration of study antibiotics (OR 1.3, 95% CI 1.026–1.552, P = 0.027) as independent predictors of the composite primary outcome. There was a trend toward lower UTI recurrence in the fosfomycin group (23% vs 12%, P = 0.06). Conclusions Our finding suggests that multidose fosfomycin is an effective agent that is noninferior to nitrofurantoin for treatment of ESBL-E lower UTI.