嗜麦芽寡养单胞菌对黏菌素的耐药特征及体外联合抗菌活性研究

目的 研究黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素及复方磺胺甲噁唑联用对多重耐药嗜麦芽寡养单胞菌的体外抗菌活性。方法 收集2015—2018年分离自温州医科大学附属第一医院的431株嗜麦芽寡养单胞菌；采用微量肉汤稀释法检测黏菌素对嗜麦芽寡养单胞菌的最低抑菌浓度(minimal inhibitory concentration, MIC)，计算逐年耐药率；通过棋盘法和微量肉汤稀释法检测黏菌素分别与氯霉素、左氧氟沙星、头孢他啶、米诺环素与复方磺胺甲噁唑联用及各自单用时对多重耐药嗜麦芽寡养单胞菌的MIC值，并通过计算部分抑菌浓度指数(FICI)评价联合抑菌效果。结果 2015—2018年间，我院嗜麦芽寡养单胞菌对黏菌素的耐药率呈现逐年上升趋势；黏菌素与氯霉素、左氧氟沙星及米诺环素联用后均表现为协同或相加作用；与头孢他啶及复方磺胺甲噁唑联用都存在无关作用，未发现拮抗作用。结论 黏菌素与氯霉素、左氧氟沙星、米诺环素联合对多重耐药嗜麦芽寡养单胞菌具有较好的体外抗菌活性，将对临床联合用药治疗多重耐药嗜麦芽寡养单胞菌的选择更具指导意义。

The tracking and investigation of resistance characteristics of Stenotrophomonas maltophilia to colistin and in vitro antibacterial activity of drug combinations with colistin#br#

Objective To investigate the in vitro antibiotic activity of colistin combined with five antibiotics (chloroamphenicol, levofloxaci, ceftazidime, minocycline, and trimethoprim/sulphamethoxazole) against multidrug-resistant Stenotrophomonas maltophilia. Methods A total of 431 Stenotrophomonas maltophilia clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2015 to 2018. Minimal inhibitory concentrations (MICs) of colistin against Stenotrophomonas maltophilia were detected by the broth dilution method, and then the annual colistin resistance rate was analyzed. MICs of colistin combined with chloroamphenicol, levofloxaci, ceftazidime, minocycline, trimethoprim/sulphamethoxazole and the five drugs used alone against the three multidrug-resistant Stenotrophomonas maltophilia were detected by the checkerboard method and the broth dilution method. Fractional inhibitory concentration index (FICI) was calculated to evaluate antibiotic effects. Results During 2015—2018, the resistance rate of Stenotrophomonas maltophilia to colistin in our hospital showed an increasing trend. The combination of colistin with chloramphenicol, levofloxacin, and minocycline showed synergistic or additive effects. There was no effect of colistin in combination with ceftazidime and trimethoprim/sulphamethoxazole, and also no antagonism was found. Conclusion The combination of colistin with chloramphenicol, levofloxacin, and minocycline has good antibacterial activity against Stenotrophomonas maltophilia in vitro, it will be more instructive for the treatment of multidrug-resistant Stenotrophomonas maltophilia in clinical combination therapy.