Journal of Global Antimicrobial Resistance (Mar 2020)

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

  • Guilian Li,
  • Jingrui Zhang,
  • Yi Jiang,
  • Li-li Zhao,
  • Haican Liu,
  • Machao Li,
  • Xiuqin Zhao,
  • Kanglin Wan

Journal volume & issue
Vol. 20
pp. 275 – 281

Abstract

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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.

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