磷霉素联合4种抗菌药物对泛耐药鲍氏不动杆菌体外活性研究

Study on antibacterial activity in vitro of fosfomycin combined with four antibiotics against extensively drug-resistant Acinetobacter baumannii

目的探讨磷霉素(FOS)与4种临床常用抗菌药物联合应用,以增强临床分离泛耐药鲍氏不动杆菌(XDRAB)体外抗菌活性。方法收集临床分离的XDRAB 50株,采用微量肉汤法和棋盘法测定FOS与左氧氟沙星、美罗培南、阿米卡星及头孢哌酮/舒巴坦4种常用抗菌药物联合使用的最低抑菌浓度(MIC),计算其部分抑菌浓度指数(FIC);用扫描电镜对比观察药物单用和联用时细菌形态变化。结果 4种抗菌药物与FOS联合使用在体外对XDRAB抗菌活性较单用增强,FOS联用美罗培南FIC值显示协同与相加作用分别占32%和46%;FOS联用左氧氟沙星(LVX)占58%和26%;FOS联用头孢哌酮/舒巴坦(CFS)占32%和54%;FOS联用阿米卡星(AMK)则占44%和38%;FIC值显示FOS与4种抗菌药物联合使用,协同与相加作用约占80%;扫描电镜观察到1/4MIC浓度的FOS单用时,细菌肿胀变形,而与其他4种抗菌药物1/4MIC联用时,细菌变形坏死。结论联合使用FOS能增强左氧氟沙星、美罗培南、阿米卡星及头孢哌酮/舒巴坦4种抗菌药物对XDRAB的抗菌活性。

OBJECTIVE To evaluate the in vitro activity of fosfomycin（FOS）in combination with four antibiotics against extensively drug-resistant A.baumannii（XDRAB）so as to intensify the in vitro antimicrobial activity of the XDRAB.METHODS Totally 50 strains of XDRAB isolated in clinic were collected.The minimal inhibitory concentrations（MICs）of FOS combined with levofloxacin,meropenem,cefperazone-sulbactam（SCF）/sulbactam and amikacin（AMK）was detected by microdilution method and chessboard method.The fractional inhibitory concentration index（FIC）was calculated according to MIC results.Morphological changes of A.baumannii was observed by scanning electron microscope.RESULTS The four antibiotics had strengthened their antibacterial activity when combined with FOS.The FIC value showed synergy or additive effect.The result showed that the additive effect of FOS＋MER,FOS＋LVX,FOS＋CFS,FOS＋AMK were 32% and 46%,58% and 26%,32% and 54%,44% and 38%respectively.They were around 80%in synergy effect and additive effect when FOS was combined with four kinds of antibiotics showed by FIC values.Antagonism effect was not observed for any combination.Scanning electron microscope founded when 1/4MIC of fosfomycin was singly used,A.baumannii became swelling and distorted,but when combined with the 4kinds of antibiotics,most of the A.baumannii distorted and died.CONCLUSIONFosfomycin will have higher antibacterial activity against XDRAB when combined with the 4kinds of antibiotics.