2. Academic Validation
  3. Cross-resistance of isoniazid, para-aminosalicylic acid and pasiniazid against isoniazid-resistant Mycobacterium tuberculosis isolates in China

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

  • J Glob Antimicrob Resist. 2020 Mar:20:275-281. doi: 10.1016/j.jgar.2019.08.005.
Guilian Li 1,  Jingrui Zhang 2,  Yi Jiang 1,  Li-Li Zhao 1,  Haican Liu 1,  Machao Li 1,  Xiuqin Zhao 1,  Kanglin Wan 3
Affiliations

Affiliations

  • 1 Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
  • 2 Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Laboratory, Shijiazhuang Obstetrics and Gynecology Hospital, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050000, China.
  • 3 Tuberculosis Branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: wankanglin@icdc.cn.
PMID: 31425771 DOI: 10.1016/j.jgar.2019.08.005
Abstract

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.

Keywords

Cross-resistance; Isoniazid; Mycobacterium tuberculosis; Para-aminosalicylic acid; Pasiniazid.

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