Synergistic Interactions of Indole-2-Carboxamides and β-Lactam Antibiotics against Mycobacterium abscessus

Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02548-19. doi: 10.1128/AAC.02548-19. Print 2020 Apr 21.

Abstract

New drugs or therapeutic combinations are urgently needed against Mycobacterium abscessus Previously, we demonstrated the potent activity of indole-2-carboxamides 6 and 12 against M. abscessus We show here that these compounds act synergistically with imipenem and cefoxitin in vitro and increase the bactericidal activity of the β-lactams against M. abscessus In addition, compound 12 also displays synergism with imipenem and cefoxitin within infected macrophages. The clinical potential of these new drug combinations requires further evaluation.

Keywords: MmpL3; Mycobacterium abscessus; drug synergism; indole-2-carboxamide; macrophage; therapeutic activity; β-lactam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cefoxitin / pharmacology
  • Colony Count, Microbial
  • Drug Synergism
  • Humans
  • Imipenem / pharmacology
  • Indoles / pharmacology*
  • Macrophages / microbiology
  • Microbial Sensitivity Tests
  • Mycobacterium Infections, Nontuberculous / drug therapy
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium abscessus / drug effects*
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Indoles
  • beta-Lactams
  • Cefoxitin
  • Imipenem