Cross-resistance of isoniazid, para-aminosalicylic acid and pasiniazid against isoniazid-resistant Mycobacterium tuberculosis isolates in China

• Main Authors: Guilian Li, Jingrui Zhang, Yi Jiang, Li-li Zhao, Haican Liu, Machao Li, Xiuqin Zhao, Kanglin Wan
• Format: Article
• Language: English
• Published: Elsevier 2020-03-01
• Series: Journal of Global Antimicrobial Resistance
• Subjects: Cross-resistance; Mycobacterium tuberculosis; Isoniazid; Pasiniazid; Para-aminosalicylic acid
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213716519302036

Objectives: Pasiniazid is a chemical complex of isoniazid (INH) and para-aminosalicylic acid (PAS). The aim of this study was to explore the cross-resistance of INH, PAS and pasiniazid against INH-resistant Mycobacterium tuberculosis isolates in China. Methods: A Microplate alamarBlue® Assay was performed to determine the minimum inhibitory concentrations (MICs) of INH, PAS and pasiniazid against 109 INH-resistant M. tuberculosis isolates. A statistical analysis of the relationship between different genotypes, gene mutations, and INH, PAS or pasiniazid susceptibility was then performed. Results: Among the 109 INH-resistant isolates, 13 (11.9%) and 21 (19.3%) showed resistance to PAS and pasiniazid, respectively. Among the 13 PAS-resistant M. tuberculosis isolates, 11 remained susceptible to pasiniazid. Of 63 INH-resistant isolates harbouring mutations in katG, the inhA promoter or the oxyR–ahpC intergenic region, 52 remained susceptible to pasiniazid. Moreover, 11 of 13 pasiniazid-resistant isolates carried mutations in katG, the inhA promoter or the oxyR–ahpC intergenic region. Conclusion: Taken together, these results demonstrate that PAS resistance and mutations in thekatG gene, inhA promoter or oxyR–ahpC intergenic region in INH-resistant M. tuberculosis have little effect on pasiniazid susceptibility.