A study on the cross-resistance character of isoniazid, para-aminosalicylic acid and pasiniazid against isoniazid resistant Mycobacterium tuberculosis in China

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 character of INH, PAS and pasiniazid against INH resistantMycobacterium tuberculosis in China. Methods A microplate Alamar blue assay was performed to determine the minimum inhibitory concentrations (MICs) of INH, PAS and pasiniazid against 109 INH resistant M. tuberculosis isolates. We then performed a statistical analysis of the relationship between different genotypes, gene mutations and INH, PAS or pasiniazid susceptibility. Results Among 109 INH resistant isolates, 11.9% (13/109) and 19.3 % (21/109) showed resistance to PAS and pasiniazid, respectively. Among 13 PAS resistantM. tuberculosis, 11 were still susceptible to pasiniazid. 52 out of 63 INH resistant isolates harboring mutations in katG, inhA promoter or oxyR-ahpC intergenic region were susceptible to pasiniazid. 11 out of 13 pasisniazid resistant isolates carried mutations in katG, inhA promoter or oxyR-ahpC intergenic region. Conclusions Taken together, our results demonstrated that PAS resistance and mutations in katG, inhA promoter or oxyR-ahpC intergenic region in INH resistant M. tuberculosis has little effect on pasiniazid susceptibility.