亚胺培南或美罗培南联合利福平降低不动杆菌防耐药突变浓度的体外研究

Study on decreasing mutant prevention concentrations of imipenem or meropenem in combination with rifampicin against Acinetobacter in vitro

目的在体外探讨亚胺培南(IMP)和美罗培南(MER)单用及其分别与利福平(RFP)联用对不动杆菌的防耐药突变浓度(MPC)的影响,为防止细菌耐药的产生提供理论依据。方法采用琼脂二倍稀释法,测定IMP或MER与RFP在体外单独以及联合应用的最低抑菌浓度(MIC)、计算部分抑菌浓度(FIC)指数。用肉汤法富集浓度为1010CFU/ml不动杆菌,采用琼脂平板二倍稀释法测定IMP和MER单药以及分别与RFP联用时对16株临床分离不动杆菌的MPC,并计算相应的选择指数(SI)。结果 IMP或MER分别与RFP联合应用后均以无关作用为主,未见拮抗作用,存在一定比例协同作用。IMP和MER单用对上述16株不动杆菌的SI均为16～128;分别与RFP联合使用SI均下降为1～32,联合用药较单独用药SI下降2～32倍。结论 IMP或MER分别与RFP联合使用均可降低其单用对不动杆菌的MPC,缩小MSW,防止耐药突变菌的产生。

Aim To investigate the mutant prevention concentrations of imipenem or meropenem alone and in combination with rifampicin against Acinetobacter in vitro,which provided evidence for new strategies for restricting the development of resistance.Methods The minimal inhibitory concentrations of imipenem,meropenem,rifampicin,imipenem or meropenem in combination with rifampicin against 16 Acinetobacter strains were tested by agar dilution method,and the fractional inhibitory concentration indexes were calculated.The cells of 10 10 colony forming units per milliliter Acinetobacter were enriched in broth.The mutant prevention concentrations of the above drugs against 16 Acinetobacter strains were detected with agar dilution method,and the selectivity indexes were calculated.Results The primary action of imipenem or meropenem in combination with rifampicin in vitro showed no interaction.The minor action was synergy.And there was no antagonistic effect observed.The selectivity indexes of imipenem and meropenem alone against 16 Acinetobacter strains were 16 ～ 128,and those of the combination application with rifampicin for Acinetobacter were both 1 ～ 32.The selectivity indexes for the combination application both decreased by 2 ～ 32-fold.Conclusion Combination application of antimicrobial agents can decrease mutant prevention concentrations of Acinetobacter,and narrow the mutant selection windows,so the emergence of resistant strains can be decreased.