多重耐药革兰阴性杆菌体外联合药效数据库初建

目的研究临床常用抗生素对多重耐药革兰阴性杆菌的协同和相加作用,初步建立体外联合药效数据库。方法选取磷霉素(PHOS)、左氧氟沙星(LEV)、头孢他啶(CAZ)、复方新诺明(SMZ)、哌拉西林/他唑巴坦(TZP)、头孢哌酮/舒巴坦(SCF)和亚胺培南(IMP)7种抗生素,两两组合为21种药物组。经超广谱β-内酰胺酶(ESBLs)和改良碳青霉烯灭活试验(mCIM)确认,172株多重耐药革兰阴性杆菌分为耐碳青霉烯肺炎克雷伯菌(20株,A组)、泛耐药的鲍曼不动杆菌(50株,B组)、产ESBLs的肠杆菌(62株,C组)和耐碳青霉烯的铜绿假单胞菌(40株,D组)4个耐药菌组。棋盘稀释法测定21种药物组对4个耐药菌组的体外联合药效,统计学分析采用Whonet5.6。结果172株待测菌株均对7种抗生素单药耐药。联合药效检测结果显示:4组均未出现拮抗作用;对A组耐药菌呈现协同作用的药物组有10组,部分协同作用的有14组,无相加作用,PHOS+LEV药物组协同百分率最高(30%,6/20);对B组耐药菌呈现协同作用的药物组有12组,部分协同作用的有10组,相加作用的有3组,LEV+SMZ药物组协同作用百分率最高(56%,28/50);对C组耐药菌呈现协同作用的药物组有14组,部分协同作用的有17组,相加作用的有16组,IMP+LEV药物组协同作用百分率最高(30.6%,19/62);对D组耐药菌呈现协同作用的药物组有12组,部分协同作用的有14组,相加作用的有13组,IMP+LEV药物组协同作用百分率最高(20%,8/40)。结论喹诺酮类、碳青霉烯类、磺胺类和磷霉素等药物联合应用,对多重耐药革兰阴性杆菌有较好的协同作用,治疗前行体外联合药效监测,可提高抗生素使用的准确性,临床应用价值较高。

Establishment of a database of in vitro combined drug efficacy against multi-drug resistant Gram-negative bacilli

Objective To study the synergistic and additive effects of commonly used antibiotics on multi-drug resistant Gram-negative bacilli and to establish a database of combined pharmacodynamics in vitro.Methods Seven antibiotics including fosfomycin(PHOS),levofloxacin(LEV),ceftazidime(CAZ),compound sulfamethoxazole(SMZ),piperacillin/tazobactam(TZP),cefoperazone/sulbactam(SCF)and imipenem(IMP)were selected and grouped into 21 drug pairs.Based on the results of extended spectrumβ-lactamases(ESBLs)test and modified carbapenem inactivation method(mCIM),a total of 172 strains of multidrug-resistant Gram-negative bacilli were divided into four groups:20 strains of carbapenem-resistant Klebsiella pneumoniae(group A),50 strains of pan-resistant Acinetobacter baumannii(group B),62 strains of ESBLs-producing Enterobacter(group C)and 40 strains of carbapenem-resistant Pseudomonas aeruginosa(group D).Chessboard dilution method was used to detect the in vitro combined efficacy of 21 drug pairs on drug-resistant bacteria from the four groups.Whonet 5.6 was used for statistical analysis.Results All 172 strains were single drug resistant to the seven antibiotics.Results of the combined drug efficacy test showed that no antagonism was found in the four groups.In group A,ten drug pairs,especially the combination of PHOS+LEV(30%,6/20),had synergistic effects and 14 showed partial synergistic effects,but no additive effect was detected.Synergistic effects,partial synergistic effects and additive effects were respectively achieved by 12,ten and three drug pairs in group B.The LEV+SMZ combination had synergistic effects against 56%(28/50)of the strains,which was the highest among all combinations.There were 14,17 and 16 drug pairs showing synergistic effects,partial synergistic effects and additive effects in group C,respectively,and the strongest synergistic effects were achieved by the IMP+LEV combination(30.6%,19/62).There were 12,14 and 13 drug pairs having synergistic effects,partial synergistic effects and additive effects in group D,respectively,and the strongest synergistic effects were achieved by the IMP+LEV combination(20%,8/40).Conclusions The combined use of quinolones,carbapenems,sulfonamides and PHOS could have good synergistic effects against multi-drug-resistant gram-negative bacilli.Monitoring the in vitro combined efficacy before treatment would improve the accuracy of antibiotic use and is of great clinical value.