Early bactericidal activity of isoniazid: Advances and implications for dosage adjustment
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Updated: Nov 5, 2026

A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
Ningjian Cai1, Xiaoyi Jiang1, Chao Zhang1
1National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China.
Abstract:
Isoniazid (INH) remains a cornerstone of tuberculosis (TB) treatment; however, its early bactericidal activity (EBA) and associated adverse effects vary substantially among individuals. Although personalized dosing has been proposed, its clinical implementation remains limited, largely due to incomplete characterization of the predictive factors. This review synthesizes evidence from PubMed-indexed EBA studies of INH to identify key determinants of its variable efficacy and to guide individualized dose selection across different clinical settings. We found that individual N-acetyltransferase 2 (NAT2) acetylator status is a critical predictor of both the EBA of INH and the risk of drug-induced liver injury (DILI). Geographic variation in NAT2 acetylator phenotypes likely explains a substantial proportion of the regional disparities in reported EBA. Additionally, escalating the INH dosage may overcome low-level resistance associated with inhA promoter mutations. In conclusion, personalizing INH dosage based on NAT2 acetylator type-especially for rapid acetylators-and increasing doses to address inhA-mediated resistance may improve therapeutic efficacy and safety. Integrating these host and pathogen factors into clinical practice could help optimize TB treatment outcomes across diverse populations and resistance profiles.
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