The ddn Trp20Stop Mutation and Its Association with Lineage 4.5 and Resistance to Delamanid and Pretomanid in Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0102622. doi: 10.1128/aac.01026-22. Epub 2022 Nov 21.

Abstract

High-confidence resistance mutations for new and repurposed anti-TB drugs, such as delamanid (DLM) and pretomanid (Pa), are rare and more data are needed in order to correctly interpret the results generated by genotypic drug susceptibility testing. In this study performed on clinical Mycobacterium tuberculosis complex isolates, we report that in the Swedish strain collection the ddn mutation Trp20Stop is found exclusively among DLM and Pa resistant (Pa MIC >16 mg/L) isolates assigned to lineage 4.5.

Keywords: Mycobacterium tuberculosis; antibiotic resistance; delamanid; pretomanid.

MeSH terms

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

Substances

  • OPC-67683
  • Antitubercular Agents
  • pretomanid
  • Nitroimidazoles