ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1688772
This article is part of the Research TopicAdvancements in Diversity and Drug Resistance Mechanisms in Mycobacterial DiseasesView all 14 articles
Determination of pyrazinamide minimum inhibitory concentrations against Mycobacterium tuberculosis clinical isolates at neutral pH 6.8 using broth microdilution method
Provisionally accepted
- 1University at Buffalo, Buffalo, United States
- 2PZA Innovation, Baltimore, MD 21215, United States
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Pyrazinamide (PZA) is a critical component of first-line tuberculosis (TB) treatment. Misdiagnosis of PZA resistance can lead to serious consequences, highlighting the need for accurate and reliable PZA susceptibility testing. While broth microdilution is a cost-effective and widely used method for determining the minimum inhibitory concentrations (MICs) of antibiotics, its current application for PZA has been limited by the requirement for acidic conditions in conventional Mycobacterium tuberculosis culture media. In this study, we determined PZA MICs against pyrazinamidase-positive M. tuberculosis clinical isolates at neutral pH 6.8 using a defined culture medium and standard protocol of broth microdilution method. Results showed that PZA MICs could be reliably determined in M. tuberculosis clinical isolates, with values ranging from ≤12.5 µg/mL to 100 µg/mL. This approach addresses the limitations of current acidic pH-based PZA susceptibility testes and provides a reliable and accurate method cost-effectively for improved PZA resistance detection. Adoption of this method could significantly enhance TB treatment, resistance surveillance, and efforts to combat drug-resistant TB.
Keywords: Mycobacterium tuberculosis, Pyrazinamide, susceptibility, minimum inhibitory concentration, isolates
Received: 19 Aug 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Tamblin, Shi, Chen and Reynolds. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jessica L. Reynolds, jlr8@buffalo.edu
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