The differential effect of clarithromycin and azithromycin on induction of macrolide resistance in Mycobacterium abscessus

Future Microbiol. 2019 Jun:14:749-755. doi: 10.2217/fmb-2018-0310. Epub 2019 Jul 4.

Abstract

Aim: Antibiotic resistance in Mycobacterium abscessus renders treatment poorly effective. Despite erm(41)-gene-mediated macrolide resistance, treatment with azithromycin or clarithromycin is recommended. It is contested whether macrolides differ in erm(41) induction. We determine whether this is the case. Methods:M. abscessus CIP104536 was used. Minimum inhibitory concentrations of clarithromycin and azithromycin were determined. Time-kill kinetics of M. abscessus exposed to azithromycin or clarithromycin were performed and RNA was isolated at predetermined intervals for erm(41) quantification. Results: Minimum inhibitory concentrations increased >30-fold. Time-kill kinetics showed a temporary bacteriostatic effect, abrogated by induced resistance. Erm(41) expression was increased following exposure to either macrolide for 7 days. Conclusion: Both macrolides induce resistance similarly, and this should not be an argument in choosing either macrolide for therapy.

Keywords: azithromycin; clarithromycin; macrolide resistance.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azithromycin / pharmacology*
  • Clarithromycin / pharmacology*
  • Drug Resistance, Bacterial / drug effects*
  • Gene Expression Profiling
  • Macrolides / pharmacology
  • Microbial Sensitivity Tests
  • Mycobacterium abscessus / drug effects*
  • RNA, Bacterial / analysis
  • RNA, Messenger / analysis
  • Transcriptional Activation / drug effects*

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • RNA, Bacterial
  • RNA, Messenger
  • Azithromycin
  • Clarithromycin