Isoniazid Resistance in Mycobacterium tuberculosis Is a Heterogeneous Phenotype Composed of Overlapping MIC Distributions with Different Underlying Resistance Mechanisms

Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00092-19. doi: 10.1128/AAC.00092-19. Print 2019 Jul.

Abstract

MIC testing using the Bactec mycobacteria growth indicator tube system 960 of 70 phylogenetically diverse, isoniazid-resistant clinical strains of Mycobacterium tuberculosis revealed a complex pattern of overlapping MIC distributions. Whole-genome sequencing explained most of the levels of resistance observed. The MIC distribution of strains with only inhA promoter mutations was split by the current concentration endorsed by the Clinical and Laboratory Standards Institute to detect low-level resistance to isoniazid and is, consequently, likely not optimally set.

Keywords: MGIT 960; MIC; Mycobacterium tuberculosis; isoniazid resistance; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Drug Resistance, Bacterial / genetics
  • Isoniazid / pharmacology*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Whole Genome Sequencing

Substances

  • Antitubercular Agents
  • Isoniazid