Pharmacokinetic analysis of nacubactam, a novel β-lactamase inhibitor, co-administered with meropenem in patients with a complicated urinary tract infection.

Objectives: Nacubactam is a novel non-β-lactam β-lactamase inhibitor being developed to treat serious Gram-negative bacterial infections. We report data from the first clinical study evaluating nacubactam intravenous (more than 1.5 h) administered to adults with presumed/confirmed complicated urinary tract infections (cUTIs), including pyelonephritis. Patients and methods: In this non-randomized, open-label study, 20 patients (mean age 51.5 years; 85.0% white; Results: Nacubactam pharmacokinetic (PK) data were similar to those obtained in prior volunteer studies. With one exception (severe nausea), adverse events (AEs) were of mild to moderate intensity, with no new safety signals, severe AEs or death. Fifty per cent had achieved joint microbiological eradication and clinical cure. Exploratory efficacy analyses in eight evaluable patients with confirmed Gram (-) cUTI identified that at follow-up (ITT population), 75.0% had achieved a clinical response of cure and 62.5% had achieved a microbiological response of eradication. Predicted PK/PD indices suggested that all 20 patients would achieve exposure targets for meropenem (minimum inhibitory concentration of 4 mg/L) and nacubactam (8 mg/L). Conclusions: The consistent PK and safety profiles of nacubactam, and the ability to align the dosing regimen with partner antibiotics, confirm the suitability of nacubactam for further clinical development in patients with Gram-negative infections.