环丝氨酸联合利福平和异烟肼对耐药结核分枝杆菌体外作用效果的研究

Study on the effects of D-Cycloserine combined with Rifampicin and Isoniazid on drug-resistant Mycobacterium tuberculosis in vitro

目的检测环丝氨酸(DCS)联合利福平和异烟肼对耐药结核分枝杆菌体外作用效果的研究。方法采用微孔板Alamar blue法测定38株临床分离株对DCS、利福平及异烟肼的最小抑菌浓度(MIC),使用棋盘稀释法检测DSC与利福平和异烟肼的体外联合作用,计算分级抑菌浓度指数(FICI)判定联合效应。结果DSC与利福平联用后,7株菌株(18.4%)表现为协同作用,24株菌株(63.2%)的联用MIC降低数个浓度梯度;DSC与异烟肼联用后,5株菌株(13.2%)表现为协同作用,22株菌株(57.9%)的联用MIC降低数个浓度梯度;两种联合药物方案均没有发现拮抗效应;DSC与利福平和异烟肼联用后MIC50和MIC90均降低。结论DSC与利福平和异烟肼联用均能不同程度地降低临床耐药株的耐药性,采用DCS联合用药有利于耐药结核病患者的治疗。

Objective To evaluate the effect of D-Cycloserine(DCS)combined with Rifampicin and Isoniazid on drug-resistant Mycobacterium tuberculosis in vitro.Methods The minimum inhibitory concentration(MIC)of 38 clinical isolates against DCS,Rifampicin and Isoniazid were determined by microporous plate Alamar Blue method,the combined effect of DSC and Rifampicin and Isoniazid in vitro was detected by checkerboard dilution method,and the combined effect was determined by fractional inhibitory concentration index(FICI).Results Seven strains(18.4%)displayed synergistic effect in DCS combination with Rifampicin,and combined MIC of 24 strains(63.2%)reduced several concentration gradients.After combined DSC with Isoniazid,5 strains(13.2%)showed synergistic effect,and the combined MIC of 22 strains(57.9%)reduced several concentration gradients.No antagonistic effect was observed with either combination drug regimen.MIC50 and MIC90 decreased after DSC combined with Rifampicin and Isoniazid.Conclusion DSC combined with Rifampicin and Isoniazid can reduce the resistance of clinical drug-resistant strains to varying degrees.DCS combined with therapy is beneficial to the treatment of drug-resistant tuberculosis patients.