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

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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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

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Acknowledgements

We thank Huimin Guo and Tao Kang for assisting the nucleotide MALDI-TOF-MS experiments and result interpretation.

Funding

This research was funded by the National Key R&D Program of China (2022YFC2305204), China CDC-Tuberculosis Control and Prevention Project (232811), and Science and technology plan project of Zhejiang Province (2023C03102).

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Author notes

  1. Xichao Ou, Zexuan Song and Bing Zhao contributed equally to this work.

Authors and Affiliations

  1. National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing, 102206, People’s Republic of China

    Xichao Ou, Zexuan Song, Bing Zhao, Ruida Xing, Yiting Wang, Shengfen Wang, Hui Xia, Yang Zhou, Ping He & Yanlin Zhao

  2. School of Public Health, Peking University, Beijing, 100191, China

    Shaojun Pei

  3. Department of Tuberculosis, Beijing Dongcheng District Center for Disease Control, Beijing, 100050, China

    Chong Teng

  4. Laboratory of Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Children’s Hospital, Capital Medical University, Beijing, 100045, China

    Huiwen Zheng

  5. Clinical Laboratory, Beijing Tong Ren Hospital, Capital Medical University, Beijing, 100730, China

    Wencong He

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Ou, X., Song, Z., Zhao, B. et al. Diagnostic efficacy of an optimized nucleotide MALDI-TOF–MS assay for anti-tuberculosis drug resistance detection. Eur J Clin Microbiol Infect Dis 43, 105–114 (2024). https://doi.org/10.1007/s10096-023-04700-y

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