以多黏菌素为基础的七种联合方案对XDR-AB体外抗菌活性的比较

Comparison of in vitro activities of seven colistin-based combination therapies against XDR-AB

目的通过体外联合药敏实验观察多黏菌素分别与利福平、亚胺培南、舒巴坦、替加环素、米诺环素、磷霉素、氯霉素联合用药对泛耐药鲍曼不动杆菌(XDR-AB)的体外抗菌活性。方法用微量肉汤稀释法分别检测多黏菌素、利福平、亚胺培南、舒巴坦、替加环素、米诺环素、磷霉素、氯霉素对XDR-AB的最小抑菌浓度(MIC),并应用棋盘法检测多黏菌素分别联合上述7种抗菌药物两两联合的MIC。根据单一用药和联合用药的MIC计算部分抑菌浓度指数(FICI),并作出协同、相加、无关及拮抗效应的判断。结果除多黏菌素与替加环素组合方案外,以多黏菌素为基础的其余联合方案对XDR-AB的体外联合效应主要表现为协同和相加效应,没有拮抗效应,具有良好的体外抗菌活性。多黏菌素联合利福平、亚胺培南、舒巴坦、米诺环素、磷霉素、氯霉素的协同及相加作用率分别为0和90%、80%和17%、0和60%、40%和50%、17%和43%、30%和60%,未观察到拮抗作用;而多黏菌素联合替加环素协同作用率为4%,相加作用率为40%,无相关作用率为36%,拮抗作用率为20%。结论多黏菌素联合利福平、亚胺培南、舒巴坦、米诺环素、磷霉素、氯霉素对XDR-AB均具有良好的体外抗菌活性,为治疗XDR-AB感染提供了重要的理论依据。

Objective To explore the in vitro activity of colistin （ COL） in combination with rifampicin （ RFP）, infipenem （ IPM ）, sul- bactam（ SUL）, tigecycline（YIG）, minocycline（ MIN）, fosfomycin（FOS） and chloramphenicol（CHL） against extensively drug resistant Acinetobacter baumannii （XDR-AB） using the microtitre plate chequerboard assay. Methods The broth microdilution method was used to determine minimal inhibitory concentration（MIC） for the 8 drugs, and then the checkerboard method was used to determine the MIC for the combined use of drugs. According to the MIC results, the values of fractional inhibitory concentration（FIC） and FIC index （FICI） were calculated. Results Except tigecycline,colistin-based combination（ COL ＋ RFP, COL ＋ IPM,COL ＋ SUL,COL ＋ MIN,COL ＋ FOS, COL ＋ CHL） had synergistic and additive effect but no antagonistic effect. The rates of synergistic and additive were 0 and 90%for COL ＋ RFP, 80% and 17% for COL ＋ IPM, 0 and 60%for COL ＋ SUL, 40% and 50% for COL ＋ MIN, 17% and 43% for COL ＋ FOS, and 30% and 60% for COL ＋ CHL, respectively. The synergistic rate of eolistin combined with tigeeyeline was 4% , additive rate was 40%, independent rate was 36% , and antagonism rate was 20%. Conclusion Compared to the monotherapy, all the eolistin-based combinations have a better activity against XDR-AB in vitro, and the eolistin-based combination may be a good alternative of therapy.