Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection

Expert Opin Drug Metab Toxicol. 2018 Oct;14(10):1007-1021. doi: 10.1080/17425255.2018.1511702. Epub 2018 Sep 19.

Abstract

Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.

Keywords: Carbapenem-resistant Enterobacteriaceae; Klebsiella pneumoniae carbapenemase; complicated urinary tract infection; meropenem; pyelonephritis; vaborbactam.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Boronic Acids / administration & dosage*
  • Boronic Acids / pharmacokinetics
  • Drug Combinations
  • Drug Resistance, Bacterial
  • Humans
  • Meropenem
  • Randomized Controlled Trials as Topic
  • Thienamycins / administration & dosage*
  • Thienamycins / pharmacokinetics
  • Urinary Tract Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Boronic Acids
  • Drug Combinations
  • Thienamycins
  • vaborbactam
  • Meropenem