The addition of avibactam renders piperacillin an effective treatment for Mycobacterium abscessus infection in an in vivo model

Antimicrob Resist Infect Control. 2018 Dec 13:7:151. doi: 10.1186/s13756-018-0448-4. eCollection 2018.

Abstract

Treating M. abscessus infection is challenging due to the potent β-lactamase BlaMab (Beta-lactamase of M. abscessus). Avibactam is a non-β-lactam, β-lactamase inhibitor shown to inhibit BlaMab. We tested whether avibactem can render piperacillin effective against M. Abscessus. In-vitro, avibactam enhanced the activity of piperacillin by 16-32 fold, with no significant effect on meropenem. In an in-vivo Galleria mellonella model, meropenem and piperacillin/avibactam significantly decreased infection burden compared to untreated controls. Neither piperacillin nor avibactam alone had a significant effect.

Keywords: Avibactam; Combination treatment; MIC; Mycobacterium abscessus; Piperacillin.

Publication types

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

MeSH terms

  • Animals
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / pharmacology
  • Azabicyclo Compounds / therapeutic use*
  • Disease Models, Animal
  • Drug Combinations
  • Drug Synergism
  • Meropenem / therapeutic use
  • Microbial Sensitivity Tests
  • Moths
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium abscessus / drug effects*
  • Piperacillin / administration & dosage
  • Piperacillin / pharmacology
  • Piperacillin / therapeutic use*
  • beta-Lactamase Inhibitors / therapeutic use*
  • beta-Lactamases

Substances

  • Azabicyclo Compounds
  • Drug Combinations
  • beta-Lactamase Inhibitors
  • avibactam
  • beta-Lactamases
  • Meropenem
  • Piperacillin