Nitrofurantoin Versus Comparators in the Treatment of Cystitis due to Extended-Spectrum β-Lactamase-Producing Enterobacterales: A Multicenter Cohort Study.

Background: The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing bacteria has limited treatment options for cystitis. The recommendation of nitrofurantoin for treatment is based solely on in vitro studies.

Objective: We aimed to evaluate the effectiveness of nitrofurantoin versus comparators in treating cystitis due to ESBL-producing Enterobacterales in the clinical setting.

Methods: This was a multicenter retrospective cohort study of afebrile adults with symptomatic cystitis and a urine culture of ≥10⁵ CFU/mL of ESBL-producing organism susceptible to nitrofurantoin and comparator antibiotics. Patients were categorized based on treatment (nitrofurantoin vs comparator). Clinical cure was the primary endpoint. Reinfection and relapse were secondary endpoints.

Results: Of 225 patients, 66 received nitrofurantoin and 159 received a comparator. Carbapenems were the most used comparator (57.2%). Clinical cure rates were not significantly different between the groups in crude (77.3% vs 86.2%; P = 0.101) and regression analyses (adjusted odds ratio [aOR], 0.82; 95% CI, 0.34-1.99). Of 35.4% of nitrofurantoin patients and 66.0% comparators group patients who had follow-up cultures, lower odds of relapse and reinfection were observed with nitrofurantoin, though not statistically significant (aOR, 0.28; 95% CI, 0.07-1.18 and aOR, 0.43 with 95% CI of 0.13-1.43, respectively). However, the inpatient setting was significantly associated with higher odds of relapse (aOR, 8.83; 95% CI, 1.07-72.74; P = 0.043).

Conclusion and relevance: Nitrofurantoin was as effective as comparators in treating cystitis due to ESBL-producing Enterobacterales. The inpatient setting was associated with higher odds of relapse. Further larger research trials are needed to validate these findings.