Melting the eis: Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New eis Promoter Variants

Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0250220. doi: 10.1128/AAC.02502-20. Epub 2021 Jun 17.

Abstract

Eis promoter mutations can confer reduced Mycobacterium tuberculosis kanamycin susceptibility. GenoType MTBDRsl, a widely used assay evaluating this region, wrongly classified 17/410 isolates as eis promoter wild type. Six out of seventeen isolates harbored mutations known to confer kanamycin resistance, and the remainder harbored either novel eis promoter mutations (7/11) or disputed mutations (4/11). GenoType MTBDRsl can miss established and new variants that cause reduced susceptibility. These data highlight the importance of reflex phenotypic kanamycin testing.

Keywords: Mycobacterium tuberculosis; extensive drug resistance; second-line injectables.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Diagnostic Tests, Routine
  • Drug Resistance, Multiple, Bacterial
  • Genotype
  • Humans
  • Kanamycin / pharmacology
  • Kanamycin Resistance / genetics
  • Microbial Sensitivity Tests
  • Mutation / genetics
  • Mycobacterium tuberculosis* / genetics
  • Tuberculosis, Multidrug-Resistant* / diagnosis
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / genetics

Substances

  • Antitubercular Agents
  • Kanamycin