In Vitro Activity of Mecillinam Against ESBL- and Non-ESBL-Producing Escherichia coli and Klebsiella pneumoniae Urinary Isolates

The rising prevalence of multidrug-resistant (MDR) Enterobacterales poses a major challenge for the empirical treatment of urinary tract infections (UTIs). We evaluated the in vitro activity of mecillinam against urinary Escherichia coli and Klebsiella pneumoniae isolates, including extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing isolates. In this prospective, single-center study conducted in Spain (December 2020–March 2021), urinary isolates of E. coli and K. pneumoniae from patients with suspected UTIs were tested for susceptibility to mecillinam and other commonly used antibiotics. A total of 503 isolates were analyzed, including 285 non-ESBL-producing and 218 ESBL-producing isolates. Overall susceptibility was 96.2% (95% CI, 94.2–97.7%) for mecillinam and 98.2% for ertapenem. Mecillinam susceptibility was 96.5% (95% CI, 93.6–98.3%) among non-ESBL-producing isolates and 95.9% (95% CI, 92.3–98.1%) among ESBL-producing isolates, with MIC50 values of 0.5 mg/L and 1 mg/L, respectively. Among ESBL-producing isolates, susceptibility to fosfomycin and trimethoprim–sulfamethoxazole was 72.9% and 44.0%, respectively. These findings demonstrate high in vitro activity of mecillinam against urinary E. coli and K. pneumoniae isolates, including both ESBL-producing and non-ESBL-producing isolates, and provide microbiological evidence supporting further clinical evaluation of pivmecillinam as an oral treatment option for UTIs.