三氯生联合抗菌药物对耐三氯生多重耐药鲍曼不动杆菌体外抗菌活性研究

In vitro antibacterial activity of triclosan in combination with different antibacterial agents against triclosan-resistant multidrug-resistant Acinetobacter baumannii

目的评价三氯生联合不同抗菌药物对耐三氯生多重耐药鲍曼不动杆菌的体外抗菌活性。方法收集2016—2017年温州医科大学附属第一医院临床分离的626株鲍曼不动杆菌,通过VITEK 2-Compact全自动微生物分析仪检测其对临床常用抗菌药物的敏感性,琼脂稀释法检测三氯生的最低抑菌浓度(MIC);采用微量棋盘稀释法检测三氯生分别与4种可作为外用膏药(庆大霉素、红霉素、氯霉素和卡那霉素)和3种临床常用的抗菌药物(亚胺培南、美罗培南和环丙沙星)联用后,各药物对16株耐三氯生多重耐药鲍曼不动杆菌的MIC值的变化,并利用部分抑菌浓度指数(FICI)评价联合抑菌效应。结果626株鲍曼不动杆菌菌株中有17株对三氯生耐药,耐药率为2.7%(17/626)。且三氯生耐药菌株对环丙沙星、亚胺培南和头孢他啶等临床常用抗菌药物有较高的MIC值,多表现为多重耐药。三氯生与7种抗菌药物联用后,各药物对16株耐三氯生多重耐药鲍曼不动杆菌的MIC值较单药MIC值均表现为不同程度降低。其中,三氯生与庆大霉素、氯霉素和环丙沙星联用后,表现为协同作用的分别有62.5%、56.25%和62.5%,相加作用的分别有37.5%、43.75%和37.5%;与红霉素、卡那霉素、亚胺培南、美罗培南联用后,表现为协同作用的分别有37.5%、25%、12.5%和12.5%,相加作用的分别有37.5%、56.25%、62.5%和62.5%,无关作用的分别有25%、18.75%、25%和25%。三氯生与上述药物联用并无拮抗作用。结论三氯生与庆大霉素、氯霉素和环丙沙星在体外联用对本组三氯生耐药的多重耐药鲍曼不动杆菌具有较好的联合抗菌活性,均表现为协同和相加作用,与卡那霉素、红霉素、亚胺培南和美罗培南联用后部分表现为无关作用,均无拮抗作用。

Objective To investigate the in vitro antibacterial activity of triclosan combined with different antibacterial agents against triclosan-resistant multidrug-resistant Acinetobacter baumannii (A.baumannii). Methods A total of 626 A. baumannii strains were collected from the First Affiliated Hospital of Wenzhou Medical University from 2016 to 2017. The sensitivity of these A. baumannii strains to common antibiotics was detected by VITEK 2-compact automatical microbiological analyzer and the minimum inhibitory concentrations (MIC) of triclosan were detected by agar dilution method. Checkerboard method was used to detect the changes in MIC values of triclosan against 16 triclosan-resistant multidrug-resistant A. baumannii strains after it was used in combination with four external ointments, including gentamicin, erythromycin, chloramphenicol and kanamycin, and three common antibiotics of imipenem, meropenem and ciprofloxacin, respectively. Fractional inhibitory concentration index (FICI) was used to evaluate the joint bacteriostatic effects. Results Among the 626 A. baumannii strains, 17 were resistant to triclosan with a drug resistance rate of 2.7%(17/626). These triclosan-resistant strains had high MIC values for ciprofloxacin, imipenem, ceftazidime and other commonly used clinical antibiotic and most of them were multidrug-resistant. After triclosan was used in combination with seven different antibacterial drugs, the MIC values of all drugs decreased to various degrees compared with those when they were used alone. Triclosan in combination with gentamicin, chloramphenicol and ciprofloxacin showed synergistic effects on 62.5%, 56.25% and 62.5% of the 16 strains and additive effects on 37.5%, 43.75% and 37.5%, respectively. When it was used in combination with erythromycin, kanamycin, imipenem and meropenem, synergistic effects on 37.5%, 25%, 12.5% and 12.5%, additive effects on 37.5%, 56.25%, 62.5% and 62.5%, and indifferent effects on 25%, 18.75%, 25% and 25% of the strains were detected, respectively. No antagonistic effect was found between triclosan and any of the above antibiotics. Conclusions Triclosan combined with gentamicin, chloramphenicol and ciprofloxacin had better in vitro antibacterial effects against the triclosan-resistant multidrug-resistant A. baumannii strains in this study with synergistic and additive effects. Some indifferent effects were found between triclosan and kanamycin, erythromycin, imipenem and meropenem, but no antagonistic effects were detected.