磷霉素与头孢哌酮/舒巴坦联用及分别联合其他抗生素对多重耐药鲍曼不动杆菌体外抗菌活性对比研究

The comparisons of fosfomycin and cefoperazone/sulbactam in combination or with other antibiotics for their in vitro antibacterial activity against multidrug-resistant Acinetobacter baumannii

目的评价磷霉素与头孢哌酮/舒巴坦作为基础药物,二者联用及分别与亚胺培南、米诺环素的联合用药方案,用于多重耐药鲍曼不动杆菌的体外联合抗菌效应对比。方法分离多重耐药鲍曼不动杆菌临床株30株,采用微量肉汤稀释棋盘法,测定不同浓度组合的抗生素联用最低抑菌浓度,并计算部分抑菌浓度指数(fractiona inhibitory concentration index,FICI)判定联合效应。将不同联合用药配伍方案进行对比,评价优劣。结果磷霉素联合亚胺培南、头孢哌酮/舒巴坦联合亚胺培南、磷霉素联合米诺环素、头孢哌酮/舒巴坦联合米诺环素、头孢哌酮/舒巴坦联合磷霉素,FIC指数分布分别为:FICI≤0.5占56.7%(17/30)、10%(3/30)、36.7%(11/30)、50%(15/30)、6.7%(2/30);0.55<FICI≤1占43.3%(13/30)、83.3%(25/30)、63.3%(19/30)、40%(12/30)、50%(15/30);1<FIC<4占0、6.7%(2/30)、0、10%(3/30)、43.3%(13/30);FIC≥4均为0。磷霉素和头孢哌酮/舒巴坦分别使联用后的亚胺培南MIC50降为单用时的1/16、1/2,MIC90降为单用时的1/8、1/2;均使联用后的米诺环素MIC50、MIC90降为单用时的1/8和1/4。结论联合用药方案对比,头孢哌酮/舒巴坦联合米诺环素最具优势,协同作用最强,优于磷霉素联合米诺环素,但提高米诺环素抗菌活性的能力相当。头孢哌酮/舒巴坦联合亚胺培南以相加、无关效应为主,试验结果可见联用后效果逊于磷霉素联合亚胺培南,且磷霉素提高亚胺培南抗菌活性的能力更强。

Objective To evaluate the in vitro antimicrobial effects of fosfomycin and cefoperazone/sulbactam as the basic drugs in combination with each other,and with imipenem and minocycline against multi-drug resistant Acinetobacter baumannii.Methods 30 clinical strains of multi-drugresistant Acinetobacter baumannii were isolated.Adopting a checkerboard design,the broth microdilution assay was used to test the effects of the compounds on the organisms.We also determined the single and combination MIC of antibacterial drugs against 30 strains of Acinetobacter baumannii and calculated the fractional inhibitory concentration(FIC)index,to judge the combination effects.Different combinations of drugs were compared to evaluate their advantages and disadvantages.Results After the combined application of fosfomycin with imipenem,cefoperazone/sulbactam with imipenem,fosfomycin with minocycline,cefoperazone/sulbactam with minocycline,or cefoperazone/sulbactam with fosfomycin,the distribution of the FIC index was as follows:FICI≤0.5 accounting for 56.7%(17/30),10%(3/30),36.7%(11/30),50%(15/30),6.7%(2/30),0.5<FICI≤1 accounting for 43.3%(13/30),83.3%(25/30),63.3%(19/30),40%(12/30),50%(15/30),1<FICI<4 accounting for 0,6.7%(2/30),0,10%(3/30),43.3%(13/30),and no antagonistic effects were observed.Fosfomycin and cefoperazone/sulbactam reduced the MIC50 of the combined drug imipenem to 1/16 and 1/2 of the single-use time,and MIC90 to 1/8 and 1/2 of the single-use time respectively;they both reduced the MIC50 and MIC90 of the combined drug minocycline to 1/8 and 1/4 of the single-use time.Conclusion Cefoperazone/sulbactam combined with minocycline had the strongest synergistic effects and is superior to fosfomycin combined with minocycline,but the ability to improve the antimicrobial activity of minocycline is comparable.Cefoperazone/sulbactam combined with imipenem had additive and irrelevant effects in most cases.The results showed that the combined effects were inferior to fosfomycin combined with imipenem,and fosfomycin had stronger ability to improve the antimicrobial activity of imipenem.