Assessment of antimycobacterial activities of pure compounds extracted from Thai medicinal plants against clarithromycin-resistant Mycobacterium abscessus

评估从泰国药用植物中提取的纯化合物对克拉霉素耐药性脓肿分枝杆菌的抗分枝杆菌活性

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作者:Auttawit Sirichoat #, Irin Kham-Ngam #, Orawee Kaewprasert, Pimjai Ananta, Awat Wisetsai, Ratsami Lekphrom, Kiatichai Faksri

Background

Infection with Mycobacterium abscessus is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against M. abscessus.

Conclusions

This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.

Methods

Twenty-three compounds were evaluated for antimycobacterial activity against thirty M. abscessus clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity.

Results

Five out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against M. abscessus, with MIC values ranging from <1 to >128 μg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%). Conclusions: This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.

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