Para-aminosalicylic acid increases the susceptibility to isoniazid in clinical isolates of Mycobacterium tuberculosis

Abstract

Tingting Zhang,1,2 Guanglu Jiang,1,2 Shu’an Wen,1,2 Fengmin Huo,1,2 Fen Wang,1,2 Hairong Huang,1,2 Yu Pang1,21National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of ChinaBackground: The purpose of this work was to assess the activity of para-aminosalicylic acid (PAS) in combination with isoniazid (INH) against clinical isolates of Mycobacterium tuberculosis (MTB).Materials and methods: A total of 72 MTB isolates with differential in vitro drug susceptibilities were included in this study, comprising 24 pan-susceptible, 24 MDR-TB, and 24 extensively drug-resistant (XDR) isolates. A microplate alamarBlue assay was performed to identify the minimal inhibitory concentrations (MICs) of MTB isolates. Results: The MIC50 of INH was 4 mg/L, and that of PAS was 0.063 mg/L against MTB isolates when single drug used. The combined use of INH and PAS resulted in 16-fold and 8-fold decrease in MIC50 for INH and PAS, respectively. The INH-PAS revealed synergistic activity in 94.4% of the isolates. In addition, there was no significant difference in the FIC index of the INH-PAS combination among individual isolates harboring different susceptibility pattern (P>0.05).Conclusion: The synergy between INH and PAS is demonstrated using non-multidrug-resistant (non-MDR) and MDR-TB strains, which will provide clinicians with useful hints to reuse this combination for treatment of TB patients in clinical practice.Keywords: Mycobacterium tuberculosis, isoniazid, para-aminosalicylic acid, synergy

Keywords

• Mycobacterium tuberculosis
• isoniazid
• para-aminosalicylic acid
• synergy