In vitro activity of sulopenem and comparator agents against US Enterobacterales clinical isolates collected during the SENTRY antimicrobial surveillance program in 2023

Abstract

Objective: Sulopenem is a thiopenem antibacterial with an oral and parenteral formulation. Sulopenem etzadroxil/probenecid, the oral formulation, was recently approved by the United States Food and Drug Administration for the treatment of women with uncomplicated urinary tract infection (UTI). This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales clinical isolates predominantly from patients with UTIs. Methods: A contemporary collection of 1086 community- and nosocomial-acquired Enterobacterales isolates was assembled from US medical centres. Isolates were susceptibility tested using the Clinical and Laboratory Standards Institute broth microdilution reference method. Results: Sulopenem demonstrated potent in vitro antimicrobial activity (MIC50/90, 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 98.0% of isolates at ≤0.5 mg/L. This activity was conserved against resistant phenotypes, including extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli (MIC50/90, 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC50/90, 0.06/0.12 mg/L). As would be expected, cross-resistance was found with imipenem and meropenem to a lesser extent. Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin-, and trimethoprim/sulfamethoxazole-non-susceptible subsets, including urinary isolates from patients in the community (MIC50/90, 0.03–0.12/0.12–0.5 mg/L). Sulopenem also maintained activity against community-acquired ESBL-producing Enterobacterales urinary isolates non-susceptible to two or more oral antimicrobial agents commonly used to treat UTIs. Conclusions: The potent in vitro activity of sulopenem against this large collection of contemporary Enterobacterales clinical isolates from multiple infection types supports its use in the treatment of uncomplicated UTI, as well as its further clinical evaluation in the treatment of other common bacterial infections demonstrating resistant phenotypes.