Gepotidacin outperformed nitrofurantoin on microbiological cure in pooled phase 3 data

Design

Pooled subgroup analysis of two phase 3 randomised trials

Population

Women and girls ≥12 years with uncomplicated UTI

Primary outcome

Therapeutic success (clinical plus microbiological) at day 10-13

Effect

+9.6 points (95% CI 4.1-15.2) susceptible; +20.8 points (9.2-32.4) non-susceptible

Gepotidacin is a first-in-class oral antibacterial. This analysis pooled two phase 3 trials, EAGLE-2 and EAGLE-3, in which women and girls aged 12 and over with uncomplicated UTI received gepotidacin 1,500 mg or nitrofurantoin 100 mg twice daily for five days. Therapeutic success at day 10-13 required both symptom resolution and microbiological clearance.

In nitrofurantoin-susceptible infections, gepotidacin's therapeutic success was 9.6 percentage points higher (95% CI 4.1-15.2), driven by microbiological success (10.4 points); clinical success alone differed by 2.8 points, an interval crossing zero. In nitrofurantoin non-susceptible infections, differences were larger: 20.8 points for therapeutic success and 20.7 for microbiological success, with clinical success again not clearly different. Results were consistent in subgroups at higher risk of resistance, including recurrent UTI, diabetes and ESBL-producing organisms.

Subgroup analyses are descriptive. Symptom resolution, which matters most to patients, did not clearly differ.

Where gepotidacin is available, it is a reasonable option when nitrofurantoin resistance is known or likely. Its status in India is not stated in this paper.

• Therapeutic success was 9.6 points higher than nitrofurantoin in susceptible infections.
• The advantage rose to about 21 points in nitrofurantoin non-susceptible infections.
• Symptom resolution alone did not clearly differ between the two drugs.
• Send a urine culture in recurrent or treatment-resistant cystitis to guide choice.
• Reserve newer agents for resistant or likely resistant infection to protect them.

Why it matters

Rising nitrofurantoin resistance leaves fewer oral options for cystitis, and this is randomised evidence for one.

Don't overread it

The advantage was mainly microbiological; symptom resolution did not clearly differ.

The statistics, in plain English

A 9.6-point difference with an interval of 4.1-15.2 is a clear advantage on the combined endpoint. The clinical-only interval crossed zero, so the symptomatic benefit is uncertain. Subgroup results describe patterns; they were not designed to prove differences.

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