Acquisition of Cross-Resistance to Bedaquiline and Clofazimine following Treatment for Tuberculosis in Pakistan

Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00915-19. doi: 10.1128/AAC.00915-19. Print 2019 Sep.

Abstract

We report on the first six cases of acquired resistance to bedaquiline in Pakistan. Seventy sequential isolates from 30 drug-resistant-tuberculosis patients on bedaquiline-containing regimens were retrospectively tested for bedaquiline resistance by MIC testing and by the detection of mutations in relevant genes. We documented cases failing therapy that developed specific mutations in Rv0678 and had increased MICs associated with cross-resistance to clofazimine during treatment. This study underlines the relevance of surveillance programs following the introduction of new drugs.

Keywords: XDR; antibiotic resistance; bedaquiline; clofazimine; multidrug resistance; tuberculosis; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Clofazimine / pharmacology*
  • Diarylquinolines / pharmacology*
  • Drug Resistance, Microbial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Pakistan
  • Retrospective Studies
  • Tuberculosis
  • Whole Genome Sequencing

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline
  • Clofazimine