Strongly Bactericidal All-Oral β-Lactam Combinations for the Treatment of Mycobacterium abscessus Lung Disease

Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0079022. doi: 10.1128/aac.00790-22. Epub 2022 Sep 1.

Abstract

Bioactive forms of oral β-lactams were screened in vitro against Mycobacterium abscessus with and without the bioactive form of the oral β-lactamase inhibitor avibactam ARX1796. Sulopenem was equally active without avibactam, while tebipenem, cefuroxime, and amoxicillin required avibactam for optimal activity. Systematic pairwise combination of the four β-lactams revealed strong bactericidal synergy for each of sulopenem, tebipenem, and cefuroxime combined with amoxicillin in the presence of avibactam. These all-oral β-lactam combinations warrant clinical evaluation.

Keywords: NTM; amoxicillin; avibactam; cefuroxime; nontuberculous mycobacteria; sulopenem; synergy; tebipenem.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Carbapenems
  • Cefuroxime
  • Humans
  • Lactams
  • Lung Diseases* / drug therapy
  • Microbial Sensitivity Tests
  • Mycobacterium abscessus*
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Carbapenems
  • Lactams
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • sulopenem
  • avibactam
  • Amoxicillin
  • beta-Lactamases
  • Cefuroxime
  • tebipenem