鸟分枝杆菌复合群对氯法齐明、贝达喹啉和德拉马尼的药物敏感性

Susceptibility of Mycobacterium avium complex to clofazimine,bedaquiline and delamanid

目的通过研究鸟分枝杆菌复合群对氯法齐明、贝达喹啉和德拉马尼的药物敏感性,初步评估其对鸟分枝杆菌复合群肺病治疗的价值。方法采用微孔板Alamar Blue法测定氯法齐明、贝达喹啉和德拉马尼对12株鸟分枝杆菌临床分离株和81株胞内分枝杆菌临床分离株的最低抑菌浓度(MIC),使用相关软件计算MIC_(50)、MIG_(90)和流行病学界值(ECOFF)。结果氯法齐明对胞内分枝杆菌的MIC_(50)和MIC_(90)分别为0.25μg/mL和0.5μg/mL,ECOFF值为0.5μg/mL;贝达喹啉对胞内分枝杆菌的MIC_(50)和MIC_(90)分别为0.125μg/mL和0.25μg/mL,ECOFF值为0.25μg/mL;德拉马尼对97.5%(79/81)胞内分枝杆菌的MIC≥256μg/mL。氯法齐明对鸟分枝杆菌的MIC_(50)和MIC_(90)分别为0.25μg/mL和0.5μg/mL,ECOFF值为0.5μg/mL;贝达喹啉对75%(9/12)的鸟分枝杆菌的MIC均为0.062 5μg/mL;德拉马尼对91.7%(11/12)的鸟分枝杆菌的MIC均为>4μg/mL。结论氯法齐明、贝达喹啉对鸟分枝杆菌复合群有较好的体外抑菌活性,德拉马尼对鸟分枝杆菌复合群无明显抑菌作用。

ObjectiveTo investigate the susceptibility of Mycobacterium avium complex to clofazimine,bedaquiline and delamanid,and therefore to explore the possibility of using these drugs to treat Mycobacterium avium complex lung disease.MethodsThe minimum inhibitory concentrations(MICs)of clofazimine,bedaquiline,and delamanid against 12 M.avium clinical isolates and 81 M.intracellulare clinical isolates were determined by using the microplate alamar blue assay(MABA).ResultsThe MIC_(50 )and MIC_(90 )of clofazimine against M.intracellulare were 0.25μg/mL and 0.5μg/mL,respectively.ECOFF of clofazimine against M.intracellulare was 0.5μg/mL.The MIC_(50 )and MIC_(90 )of bedaquiline against M.intracellulare were 0.125μg/mL and 0.25μg/mL,respectively.ECOFF of bedaquiline against M.intracellulare was 0.25μg/mL.The MICs of delamanid against 97.5%(79/81)of M.intracellulare clinical isolates were≥256μg/mL.The MIC_(50 )and MIC_(90 )of clofazimine against M.avium were 0.25μg/mL and 0.5μg/mL,respectively.ECOFF of clofazimine against M.avium was 0.5μg/mL.The MICs of bedaquiline against 75%(9/12)of M.avium clinical isolates were 0.0625μg/mL;and the MICs of delamanid against 91.7%(11/12)of M.avium clinical isolates were>4μg/mL.ConclusionsClofazimine and bedaquiline showed acceptable in vitro activity against M.avium complex,and Delamanid has no effect on M.avium complex.