Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis.

BACKGROUND

Antimicrobial resistance threatens oral treatment options for acute uncomplicated urinary tract infection (uUTI). Gepotidacin (Blujepa) is a novel oral triazaacenaphthylene antibiotic evaluated in Phase 3 trials versus nitrofurantoin.

OBJECTIVES

To pool Phase 3 randomized evidence comparing gepotidacin and nitrofurantoin for efficacy and safety in female uUTI.

METHODS

PRISMA-compliant systematic review and random-effects meta-analysis of Phase 3 randomized controlled trials. Two investigators independently screened records (using Rayyan), extracted data and assessed risk of bias with RoB 2; certainty was rated with GRADE. Outcomes were pooled as risk ratios (RR) or mean differences with 95% confidence intervals (CI) using RevMan 5.4.

RESULTS

Three trials (EAGLE-2, EAGLE-3 and EAGLE-J) including 3510 participants (gepotidacin n = 1853; nitrofurantoin n = 1657) were included. Gepotidacin increased composite therapeutic success versus nitrofurantoin (RR 1.20; 95% CI 1.10-1.31; I2 = 0%; P < 0.001) and improved microbiological eradication (RR 1.14; 95% CI 1.07-1.21; I2 = 2%; P < 0.001). Gastrointestinal adverse events were more frequent with gepotidacin (diarrhoea RR 5.51; 95% CI 4.08-7.45; nausea RR 2.49; 95% CI 1.56-3.97). Serious adverse events were rare and similar between groups. Certainty of evidence per outcome is presented in Table S2 (available as Supplementary data at JAC Online).

CONCLUSIONS

Gepotidacin provides superior composite and microbiological outcomes relative to nitrofurantoin for female uUTI but is associated with increased mild-to-moderate gastrointestinal toxicity. Long-term tolerability and resistance surveillance are recommended.