Meropenem-vaborbactam: a carbapenem and beta-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae

Meropenem-vaborbactam is a carbapenem and beta-lactamase inhibitor combination that is newly indicated for the treatment of complicated urinary tract infections (cUTI), including adult pyelonephritis. Vaborbactam was developed due to emergence of carbapenem-resistant strains of Enterobacteriaceae. In a phase I trial, patients that received meropenem-vaborbactam 2-2 g intravenously over 3 h every 8 h, C (max) was 58.2 +/- 10.8 mu g/mL for meropenem and 59.0 +/- 8.4 mu g/mL for vaborbactam. AUC(0-8) was 186 +/- 33.6 mu g aEuro cent h/mL for meropenem and 204 +/- 34.6 mu g aEuro cent h/mL for vaborbactam. V (ss) = 16.3 +/- 2.6 L for meropenem and 17.6 +/- 2.6 L for vaborbactam. Protein binding for vaborbactam averaged 33% in humans. Plasma clearance ranged from 10.42 +/- 1.85 to 14.77 +/- 2.84 L/h. One phase III trial evaluated efficacy for meropenem-vaborbactam 2-2 g intravenously every 8 h versus piperacillin-tazobactam 4-0.5 g intravenously every 8 h in complicated UTI. It found non-inferiority and statistical superiority for meropenem in overall success at the end of treatment primary end point. In another phase III trial evaluating efficacy in carbapenem-resistant Enterobacteriaceae (CRE) infections, meropenem-vaborbactam 2-2 g intravenously every 8 h was associated with decreased 28-day mortality and increased clinical cure compared with a best available therapy group.