Escherichia coli Nissle 1917 for the prevention of recurrent uncomplicated urinary tract infections in women: a pilot randomized placebo-controlled trial

BACKGROUND: Recurrent urinary tract infections (rUTIs) represent a common clinical condition in women and are frequently associated with repeated antibiotic exposure. Increasing interest has therefore focused on non-antimicrobial preventive strategies. Escherichia coli Nissle 1917 (EcN) is a probiotic strain with documented antagonistic activity against uropathogens, although clinical evidence supporting its use in adult women with rUTIs remains limited. OBJECTIVE: To evaluate the efficacy and safety of EcN compared with placebo in women with recurrent uncomplicated urinary tract infections. Materials and methods: This pilot multicentre double-blind randomized placebo-controlled trial enrolled 50 women with recurrent uncomplicated UTIs. Patients were randomized to receive EcN or placebo and followed for 26 weeks. The primary endpoint was the occurrence of at least one microbiological recurrence during follow-up. Secondary endpoints included number of recurrences, time to first recurrence, urine culture results at scheduled follow-up visits, and patient-reported outcomes assessed using SF-36, PPBC, and PGI-I questionnaires. RESULTS: Fifty patients were included in the analysis (EcN n = 24; placebo n = 26). At least one microbiological recurrence during follow-up occurred in 4/24 patients (16.7%) treated with EcN compared with 11/26 patients (42.3%) receiving placebo, corresponding to a relative risk (RR) of 0.39 (95% CI 0.14-1.14; p = 0.089). Positive urine cultures at 12 weeks were less frequent in the EcN group compared with placebo (8.3% vs 23.1%). Kaplan-Meier analysis showed a numerically favourable recurrence- free survival trend for EcN-treated patients during follow-up. Global SF-36 scores improved in both groups, while exploratory analysis of SF-36 domains demonstrated a significantly greater improvement in the Vitality domain at 24 weeks in patients receiving EcN (Δ + 0.165 vs + 0.021; p = 0.041). PPBC and PGI-I scores also showed a trend toward benefit for EcN throughout follow-up. EcN was generally well tolerated, with mild gastrointestinal adverse events representing the most commonly reported side effects. CONCLUSIONS: EcN showed promising signals toward reduction of recurrent urinary tract infections and improvement in patientreported outcomes, particularly vitality-related quality-of-life measures. Although limited by the pilot nature of the study and the reduced sample size due to recruitment difficulties during the COVID-19 pandemic, the present findings support further adequately powered randomized trials investigating EcN as a non-antimicrobial preventive strategy in women with recurrent uncomplicated UTIs.