In vitro efficacy of combinations of eight antimicrobial agents against Mycobacteroides abscessus complex

Int J Infect Dis. 2020 Aug:97:270-277. doi: 10.1016/j.ijid.2020.06.007. Epub 2020 Jun 9.

Abstract

Objectives: A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections.

Methods: We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method.

Results: We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively.

Conclusions: These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.

Keywords: Mycobacteroides abscessus complex; checkerboard assay; drug susceptibility testing; imipenem.

MeSH terms

  • Actinomycetales Infections / microbiology
  • Amikacin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / pharmacology
  • Doxycycline / pharmacology
  • Humans
  • Imipenem / pharmacology
  • Linezolid / pharmacology
  • Microbial Sensitivity Tests
  • Moxifloxacin / pharmacology
  • Mycobacteriaceae / classification
  • Mycobacteriaceae / drug effects*
  • Mycobacteriaceae / growth & development
  • Sequence Analysis, DNA
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Imipenem
  • Amikacin
  • fropenem
  • Clarithromycin
  • Linezolid
  • Doxycycline
  • Moxifloxacin