Meropenem/vaborbactam: a next generation β-lactam β-lactamase inhibitor combination

Expert Rev Anti Infect Ther. 2020 Jul;18(7):643-655. doi: 10.1080/14787210.2020.1756775. Epub 2020 May 3.

Abstract

Introduction: infections due to carbapenem-resistant Enterobacterales (CRE) constitute a worldwide threat and are associated with significant mortality, especially in fragile patients, and costs. Meropenem-vaborbactam (M/V) is a combination of a group 2 carbapenem with a novel cyclic boronic acid-based β-lactamase inhibitor which has shown good efficacy against KPC carbapenemase-producing Klebsiella pneumoniae, which are amongst the most prevalent types of CRE.

Areas covered: This article reviews the microbiological and pharmacological profile and current clinical experience and safety of M/V in the treatment of infections caused by CRE.

Expert opinion: M/V is a promising drug for the treatment of infections due to KPC-producing CRE (KPC-CRE). It exhibited an almost complete coverage of KPC-CRE isolates from large surveillance studies and a low propensity for resistance selection, retaining activity also against strains producing KPC mutants resistant to ceftazidime-avibactam. Both meropenem and vaborbactam have a favorable pharmacokinetic profile, with similar kinetic properties, a good intrapulmonary penetration, and are efficiently cleared during continuous venovenous hemofiltration (CVVH). According to available data, M/V monotherapy is associated with higher clinical cure rates and lower rates of adverse events, especially in terms of nephrotoxicity, if compared to 'older' combination therapies.

Keywords: Carbapenem-Resistant Enterobacterales (CRE); KPC carbapenemase; KPC-producing Klebsiella pneumoniae; meropenem-vaborbactam (M/V).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Boronic Acids / administration & dosage*
  • Boronic Acids / pharmacokinetics
  • Boronic Acids / pharmacology
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Drug Combinations
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Hemofiltration
  • Heterocyclic Compounds, 1-Ring / administration & dosage*
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Meropenem / administration & dosage*
  • Meropenem / pharmacokinetics
  • Meropenem / pharmacology
  • Tissue Distribution
  • beta-Lactamase Inhibitors / administration & dosage
  • beta-Lactamase Inhibitors / pharmacokinetics
  • beta-Lactamase Inhibitors / pharmacology

Substances

  • Anti-Bacterial Agents
  • Boronic Acids
  • Drug Combinations
  • Heterocyclic Compounds, 1-Ring
  • beta-Lactamase Inhibitors
  • meropenem and vaborbactam
  • Meropenem