The <i>ahpC</i> c−54t compensatory mutation is not always a valid surrogate for isoniazid resistance in <i>Mycobacterium tuberculosis</i>
Thirteen commercial genotypic antimicrobial susceptibility assays interrogate mutations upstream of <i>ahpC</i> to infer isoniazid resistance for <i>Mycobacterium tuberculosis</i>. We demonstrate that relying on one of these compensatory mutations (i.e., <i>ahpC</i> c-54t)-rather than causative resistance mutations in <i>katG</i> that <i>ahpC</i> compensates for-can result in systematic false-resistant results for isoniazid with the Cepheid Xpert MTB/XDR and suboptimal treatment. The WHO mutation catalog should be refined to address this scenario.
Authors
- Sophia B. Georghiou (ORCID: https://orcid.org/0000-0003-0099-903X)
- David L. Dolinger
- Claudio U. Köser (ORCID: https://orcid.org/0000-0002-0232-846X)
- Taane Gregory Clark (ORCID: https://orcid.org/0000-0001-8985-9265)
- Jody Phelan (ORCID: https://orcid.org/0000-0001-8323-7019)
- Stefan Niemann (ORCID: https://orcid.org/0000-0002-6604-0684)
- Lilla Lörinczi
- Viktória Szél
Institutions
- University of Cambridge (GB)
- London School of Hygiene & Tropical Medicine (GB)
- German Center for Infection Research (DE)
- Research Center Borstel - Leibniz Lung Center (DE)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1128/aac.00265-25
- Citations
- 1
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- UK Research and Innovation
- Deutsche Forschungsgemeinschaft