Diagnostic efficacy of an optimized nucleotide MALDI-TOF-MS assay for anti-tuberculosis drug resistance detection

Eur J Clin Microbiol Infect Dis. 2024 Jan;43(1):105-114. doi: 10.1007/s10096-023-04700-y. Epub 2023 Nov 18.

Abstract

Purpose: We aimed at evaluating the diagnostic efficacy of a nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay to detect drug resistance of Mycobacterium tuberculosis.

Methods: Overall, 263 M. tuberculosis clinical isolates were selected to evaluate the performance of nucleic MALDI-TOF-MS for rifampin (RIF), isoniazid (INH), ethambutol (EMB), moxifloxacin (MXF), streptomycin (SM), and pyrazinamide (PZA) resistance detection. The results for RIF, INH, EMB, and MXF were compared with phenotypic microbroth dilution drug susceptibility testing (DST) and whole-genome sequencing (WGS), and the results for SM and PZA were compared with those obtained by WGS.

Results: Using DST as the gold standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 98.2%, 98.7%, and 0.97 for RIF; 92.8%, 99%, and 0.90 for INH; 82.4%, 98.0%, and 0.82 for EMB; and 92.6%, 99.5%, and 0.94 for MXF, respectively. Compared with WGS as the reference standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 97.4%, 100.0%, and 0.98 for RIF; 98.7%, 92.9%, and 0.92 for INH; 96.3%, 100.0%, and 0.98 for EMB; 98.1%, 100.0%, and 0.99 for MXF; 98.0%, 100.0%, and 0.98 for SM; and 50.0%, 100.0%, and 0.65 for PZA.

Conclusion: The nucleotide MALDI-TOF-MS assay yielded highly consistent results compared to DST and WGS, suggesting that it is a promising tool for the rapid detection of sensitivity to RIF, INH, EMB, and MXF.

Keywords: Drug resistance; Drug susceptibility testing; Mycobacterium tuberculosis; Nucleotide MALDI-TOF–MS.

MeSH terms

  • Antitubercular Agents / pharmacology
  • Ethambutol
  • Humans
  • Isoniazid
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis*
  • Rifampin
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Streptomycin
  • Tuberculosis, Multidrug-Resistant* / diagnosis
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Antitubercular Agents
  • Streptomycin
  • Ethambutol
  • Isoniazid
  • Rifampin