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目的体外观察β-内酰胺类抗菌药物能否诱导产生异质性万古霉素中介金黄色葡萄球菌(hVISA),并对其进行药敏试验。方法挑选医院2015年8月-10月临床MRSA 5株,选择头孢他啶、哌拉西林/他唑巴坦、美罗培南3种常用β-内酰胺药物,逐步诱导菌株,应用菌群分析曲线法检测hVISA,E-test法测定hVISA对万古霉素、利奈唑胺、替加环素、达托霉素的MIC,棋盘格法测定联合药敏试验。结果 3种β-内酰胺类抗菌药物诱导产生的hVISA菌株分别为3株、3株、1株。7株hVISA对万古霉素的MIC范围在2~4mg/L,联合利福平、左氧氟沙星、夫西地酸药物后,hVISA对万古霉素的MIC范围分别为1~4mg/L,1~4mg/L,1~2mg/L,对利奈唑胺、替加环素、达托霉素的MIC范围分别为0.25~1mg/L,0.125~0.5mg/L,0.064~0.25mg/L。结论体外β-内酰胺类抗菌药物可以诱导产生hVISA,头孢类与半合成青霉素类较碳青霉烯类抗菌药物更容易诱导产生hVISA,联合用药不能显著降低hVSA对万古霉素的MIC值,新型治疗MRSA药物利奈唑胺、替加环素、达托霉素对hVISA均较为敏感,可有效治疗hVISA感染。
Objective To observe whether β-lactam antibiotics can induce heterogeneous vancomycin-mediated staphylococcus aureus (hVISA) in vitro and conduct drug susceptibility testing. Methods Five clinical MRSA patients were selected from August 2015 to October 2015 in our hospital. Three commonly used β-lactam drugs, ceftazidime, piperacillin / tazobactam, and meropenem, were selected to induce the strains gradually. Microbial population analysis was used to detect hVISA E-test method was used to determine the MIC of hVISA to vancomycin, linezolid, tigecycline and daptomycin. Results Three strains of hVISA induced by three kinds of β-lactam antibiotics were 3, 3 and 1, respectively. The range of MIC of hVISA against vancomycin was 2 ~ 4 mg / L for 7 strains of hVISA, and the range of MIC of hVISA to vancomycin was 1 ~ 4 mg / L and 1 ~ 4 mg, respectively after combining rifampicin, levofloxacin and fusidic acid / L, 1 ~ 2mg / L for linezolid, tigecycline, daptomycin MIC range of 0.25 ~ 1mg / L, 0.125 ~ 0.5mg / L, 0.064 ~ 0.25mg / Conclusion In vitro β-lactam antibiotics can induce hVISA, and cephalosporins and semi-synthetic penicillins are more likely to induce hVISA than carbapenems. Combination therapy can not significantly reduce the MIC of hVSA against vancomycin. The treatment of MRSA drug linezolid, tigecycline, daptomycin hVISA are more sensitive, effective treatment of hVISA infection.