β-内酰胺类抗菌药物诱导异质性万古霉素中介金黄色葡萄球菌及其药敏试验研究

Exposure of beta-lactam antibiotics inducing heterogeneous vancomycin intermediate Staphylococcus aureus and its drug sensitive test

  • 摘要: 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2~4 mg/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1~4 mg/L,1~4 mg/L,1~2 mg/L,对利奈唑胺、替加环素、达托霉素的MIC范围分别为0.25~1 mg/L,0.125~0.5 mg/L,0.064~0.25 mg/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。

     

    Abstract: OBJECTIVE To determine whether exposure to beta-lactam antibiotics can induce heterogeneous vancomycin intermediate Staphylococcus aureus(hVISA) in vitro, and carry out its drug sensitive test. METHODS Five clinical strains of methicillin-resistant Staphylococcus aureus(MRSA) were selected, and three commonly used β-lactam antibiotics (ceftazidime, piperacillin-tazobactam and meropenem) were used to gradually induce the strains. The strains after induction were classified as hVISA according to the method of PAP/AUC. The MIC of vancomycin, linezolid, tigecycline and daptomycin against hVISA were determined by E-test, and the combined drug sensitivity was determined by checkerboard method. RESULTS Three, three and one hVISA strains were induced by ceftazidime, piperacillin-tazobactam and meropenem, respectively. The MIC of seven hVISA strains to vancomycin were 2-4mg/L. The MIC of hVISA to vancomycin combined with rifampin, levofloxacin and fusidic acid were 1-4mg/L, 1-4 mg/L and 1-2mg/L, respectively. The MIC to linezolid, tigecycline and daptomycin were 0.25-1 mg/L, 0.125-0.5 mg/L and 0.064-0.25 mg/L, respectively. CONCLUSION The hVISA strains can be induced by beta-lactam antibiotics in vitro. The cephalosporin and semi-synthetic penicillin are easier to induce hVISA stains than carbapenems. Combined medication can not be a significant reduction in MIC of hVISA to vancomycin. The new antibiotics (linezolid, tigecycline and daptomycin) against MRSA have higher sensitivity to hVISA, which can effectively treat the infection by hVISA.

     

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