Pivmecillinam for Treatment of Uncomplicated Urinary Tract Infection: New Efficacy Analysis.

Background: In April 2024-over 40 years after its first approval in Europe-pivmecillinam received approval from the United States Food and Drug Administration (FDA) for the treatment of uncomplicated urinary tract infection (uUTI) in women aged ≥18 years, caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. Herein, we describe the reanalysis from previously published clinical trials, conducted in accordance with current FDA efficacy criteria, which formed the basis for this regulatory approval.

Methods: Of 14 studies reviewed, 3 randomized, controlled trials offered suitable subject-level data from patients with uUTI treated with 185 mg pivmecillinam 3 times daily for 3-7 days. Efficacy endpoints for reanalysis were rates of overall (composite clinical and microbiological), clinical, and microbiological response in the microbiological intention-to-treat population (urine culture ≥105 colony-forming units/mL; ≤2 microorganism species; no baseline pathogen nonsusceptible to active comparator).

Results: Across the 3 primary studies, overall success rates with pivmecillinam at test of cure (Days 7-15) were 62.0%-71.7% (clinical success, 63.5%-82.7%; microbiological success, 74.3%-86.9%). Overall success was higher for pivmecillinam than for placebo (95% confidence interval for the difference, 41.2-62.0) or ibuprofen (31.2-56.5) and similar to cephalexin (-15.6 to 7.4). Response to pivmecillinam was demonstrated in uUTIs caused by Enterobacterales, including E. coli, P. mirabilis, and Klebsiella pneumoniae, as well as gram-positive S. saprophyticus.

Conclusions: This reanalysis of randomized, controlled trial data confirmed the efficacy of oral pivmecillinam in uUTI and was used to support its recent approval in the United States.