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

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Abstract

Meropenem-vaborbactam is a carbapenem and β-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, Cmax was 58.2 ± 10.8 μg/mL for meropenem and 59.0 ± 8.4 μg/mL for vaborbactam. AUC0–8 was 186 ± 33.6 μg • h/mL for meropenem and 204 ± 34.6 μg • h/mL for vaborbactam. Vss = 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.

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Authors and Affiliations

  1. School of Pharmacy, Texas Tech University Health Sciences Center, 1718 Pine Street, Abilene, TX, 79601, USA

    Young R. Lee & Nathaniel T. Baker

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  1. Young R. Lee
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  2. Nathaniel T. Baker
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Correspondence to Young R. Lee.

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Key Points

• Meropenem-vaborbactam is a newly developed carbapenem and β-lactamase inhibitor indicated for complicated UTI and targets resistance mechanism KPC and KPC-like carbapenemases.

• Meropenem-vaborbactam has been found non-inferior to piperacillin-tazobactam for treatment of acute pyelonephritis in phase III study.

• Phase I and III studies report no serious adverse events with meropenem-vaborbactam, making it a safer choice over aminoglycosides, colistin, and tigecycline.

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Lee, Y.R., Baker, N.T. Meropenem-vaborbactam: a carbapenem and beta-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae. Eur J Clin Microbiol Infect Dis 37, 1411–1419 (2018). https://doi.org/10.1007/s10096-018-3260-4

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  • DOI: https://doi.org/10.1007/s10096-018-3260-4

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