刃天青法检测青蒿琥酯对耐药结核分枝杆菌药物敏感性初步研究

目的 了解青蒿琥酯(artesunate,ASN)单独或联合利福平(rifampicin,RFP)、异烟胼(isoniazid,INH)、链霉素(streptomycin,SM)、氧氟沙星(ofloxacin,OFLX)等抗结核药物对耐药结核分枝杆菌的抑制作用,为耐药结核的治疗寻找新的有效药物提供依据.方法 采用刃天青法检测ASN对耐药结核分枝杆菌的抑制作用,并采用ASN联合RFP、INH、OFLX、SM对耐药结核分枝杆菌抗结核药物MIC研究.结果 本研究测试的14株耐药菌株中,7株MIC值为256μg/mL,6株MIC值为128μg/mL,1株MIC为512μg/mL,MIC50为256μg/mL,MIC90为256μg/mL.16株敏感株中,MIC50为128μg/mL,MIC90为256μg/mL.两者差异无统计学意义(P＞0.05).此外,当ASN终浓度为32 ～ 128μg/mL时,能明显改善耐药MTB对RFP、INH、OFLX、SM等抗结核药物的敏感性.结论 ASN对抗耐药结核分枝杆菌作用可能甚微,但其能协同或逆转抗结核药物改善耐药MTB的药物敏感性,可能成为耐多药结核治疗备选新药.

Preliminary Study on the Effect of Artesunate to Drug-resistantce Mycobacterium Tuberculosis Detected by Resazurin Method

Objective To investigate the effect of artesunate (ASN)on resistant Mycobacterium tuberculosis alone or in combination with rifampicin (RFP),isoniazid (INH),Ofloxacin (OFLX),streptomycin (SM),and provide a basis for finding new and effective drug for treatment of MDR-TB.Methods ASN was detected to inhibit resistant Mycobacterium tuberculosis by Resazurin method,and the MICs of resistant Mycobacterium tuberculosis to RFP,INH,OFLX,SM in combination with ASN were studied.Results The MIC values of ASN to seven strains,six strains and one strain were 256μg/mL,128μg/mL and 512μg/mL.The MIC50 of ASN to 14 resistant isolates was 256 μg/mL,and MIC90 was 256μg/mL.The MIC50 of ASN to 16 sensitive isolates was 128μg/mL,and MIC90 was 256μg/mL.There was no significant difference between two groups (P ＞0.05).In addition,when the concentration of ASN was 32-128μg/mL,it significantly improved the drug sensitivity of RFP,INH,OFLX and SM in resistant Mycobacterium tuberculosis.Conclusion ASN has a faint inhibitory effect on resistant Mycobacterium tuberculosis,but it can reverse the MIC of RFP,INH,OFLX and SM-resistant Mycobacterium tuberculosis,and may become a new drug for multidrug-resistant Mycobacterium tuberculosis treatment.