Rapid detection of clarithromycin resistance in clinical samples of nontuberculous mycobacteria by nucleotide MALDI-TOF MS

J Microbiol Methods. 2024 Apr:219:106894. doi: 10.1016/j.mimet.2024.106894. Epub 2024 Feb 5.

Abstract

The multidrug resistance of nontuberculous mycobacteria (NTM) poses a significant therapeutic challenge. Rapid and reliable drug susceptibility testing is urgently needed for evidence-based treatment decision, especially for macrolides. This study evaluated the utility of nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (NMTMS) in detecting clarithromycin resistance. Sixty-four clinical isolates were identified to species by NMTMS, and mutations associated with clarithromycin resistance were detected. Twenty-three M. abscessus (MAB) isolates and 30 M. intracellulare isolates (including M. intracellulare alone and M. intracellulare in combination with other SGM species) were included for analysis. The predictive sensitivity of NMTMS in detecting clarithromycin resistance was 82.35% (95% CI, 56.57% to 96.20%), with an AUC of 0.89 (95% CI, 0.77 to 0.96) in all MAB and M. intracellulare (n = 53), and up to 93.33% (95% CI, 68.05% to 99.83%) in MAB alone (n = 23). The assay provides a rapid, high-throughput, and highly sensitive tool for detecting clarithromycin resistance in NTM, especially in MAB. Optimization of the panel is necessary to enhance diagnostic accuracy.

Keywords: Clarithromycin; Drug resistance; Nontuberculous Mycobacterium; Nucleotide MALDI-TOF MS; Rapid detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clarithromycin / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium Infections, Nontuberculous* / diagnosis
  • Mycobacterium tuberculosis*
  • Nontuberculous Mycobacteria
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods

Substances

  • Clarithromycin