Analysis of drug-susceptibility patterns and gene sequences associated with clarithromycin and amikacin resistance in serial Mycobacterium abscessus isolates from clinical specimens from Northeast Thailand

PLoS One. 2018 Nov 29;13(11):e0208053. doi: 10.1371/journal.pone.0208053. eCollection 2018.

Abstract

Mycobacterium abscessus is an important infectious agent highly associated with drug resistance and treatment failure. We investigated the drug resistance situation of M. abscessus in Northeast Thailand and the possible genetic basis for this. Sixty-eight M. abscessus clinical isolates were obtained from 26 patients at Srinagarind Hospital during 2012-2016. Drug susceptibility tests and sequencing of erm(41), rrl and rrs genes were performed. Mycobacterium abscessus was resistant to 11/15 antibiotics (nearly 100% resistance in each case). Partial susceptibility to four antibiotics was found (amikacin, tigecycline, clarithromycin and linezolid). Non-massiliense subspecies were significantly associated with clarithromycin resistance (p<0.0001) whereas massiliense subspecies were associated with tigecycline resistance (p = 0.028). Inducible clarithromycin resistance was seen in 22/68 (32.35%) isolates: 21 of these isolates (95.45%) belonged to non-massiliense subspecies and resistance was explicable by the T28C mutation in erm(41). Inducible clarithromycin resistance was found in one isolate of the massiliense subspecies. Acquired clarithromycin resistance explicable by the A2271G/C mutation of rrl was seen in only 7/16 (43.75%) of strains. Inducible and acquired resistance mechanisms can be interchangeable during the course of infection. Rrs mutations were not associated with amikacin resistance in our study. Antibiotic resistance in subspecies of M. abscessus was reported from Northeast Thailand. Known resistance-associated mutations cannot explain all of the resistance patterns observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amikacin / pharmacology
  • Anti-Bacterial Agents
  • Clarithromycin / pharmacology
  • Drug Resistance, Bacterial / genetics*
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium / drug effects
  • Mycobacterium / genetics
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / genetics
  • Mycobacterium abscessus / drug effects
  • Mycobacterium abscessus / genetics*
  • Mycobacterium abscessus / pathogenicity
  • Sequence Analysis, DNA
  • Thailand / epidemiology

Substances

  • Anti-Bacterial Agents
  • Amikacin
  • Clarithromycin

Grants and funding

This study was financially supported by General Supportive Grant, Khon Kaen University, Thailand 2019 (Grant number: 6200039).This grant provided only research budget and no publication fee budget was provided. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.