利奈唑胺与其他抗生素联用对耐甲氧西林黄色葡萄球菌体外抗菌活性研究

摘要

目的 探讨利奈唑胺与3种常用抗生素(利福平、左氧氟沙星、庆大霉素素)分别联用对临床分离的耐甲氧西林黄色葡萄球菌(MRSA)的体外抗菌活性,为临床有效地治疗MRSA感染提供理论依据.方法 常规方法培养分离细菌,获得纯培养后用VITEK全自动微生物分析仪来鉴定金黄色葡萄球菌,再根据CLSI(2006)标准,用微量肉汤法用苯唑西林测定MIC值,判定结果MIC值≥4 μg/ml为MRSA菌株.药敏试验方法采用微量肉汤稀释法.先测定四种抗菌药物单独应用受试的MIC值.联合药敏试验按棋盘法设计,测定利奈唑胺与其他3种抗生素联用的MIC.计算部分抑菌浓度(FIC)指数,FIC指数=MIC甲药联用/MIC甲药单用+MIC乙药联用/MIC乙药单用.判读标准:FIC指数≤0.5,协同作用；＞0.5～1.0,相加作用；＞1.0～2.0,无相关作用；＞2.0,拮抗作用.结果 利奈唑胺对30株MRSA的MIC范围为0.5～4.0 μg/ml,MIC90为4μg,/ml；左氧氟沙星对30株MRSA的MIC范围为16～256 μg/ml,MIC90为256 μg/ml；利福平对30株MRSA的MIC范围为8～256 μg/ml,MIC90为256 μg/ml；庆大霉素对30株MRSA的MIC范围为128～ 1024 μg/ml,MIC90为1024 μg/ml.利奈唑胺与左氧氟沙星联用MIC90降为2μg/rml,利奈唑胺与利福平联用MIC90降为lμg/ml,利奈唑胺与庆大霉素联用MIC90降为2μg/ml.结论 利奈唑胺对MRSA有较高敏感性,利奈唑胺与利福平联合应用以协同作用为主,利奈唑胺与左氧氟沙星、庆大霉素联合应用以协同和相加作用为主,二者均无拮抗作用.%Objective To investigate the antibacterial activity of linezolid combined with three kinds of commonly used antibiotics ( rifampicin,levofloxacin,gentamicin) against MRSA in vitro,and provide basis for treating MRSA infection in clinic.Methods Bacteria were isolated by conventional methods to obtain pure cultured microorganism with the VITEK automatic analyzer to identify Staphylococcus aureus,and then according to CLSI (2006) standard,the broth method with the determination of oxacillin minimal inhibitory concentr ation (MIC) values,MIC value determined result ≥ 4 μg/ml for the MRSA strain.Broth dilution method was used to test the susceptibility.Determination of four kinds of antimicrobial drugs first tested the MIC values alone.The combined sensitivity test method designed by the board to determine linezolid in conjunction with the other three kinds of antibiotics used for MIC.Inhibition index calculated part of the FIC (fractional inhibitory concentration index).FIC index =MIC Adrug combined with / MIC A drug alone + MIC B drugs combination / MIC B drug alone.Interpretation of standards:FIC index ≤0.5,synergy; ＞0.5 - 1.0,Additive effect; ＞ 1.0 -2.0,no relevant effect; ＞2.0,antagonism.Results Linezolid MIC against 30 strains of MRSA in the range of 0.5 -4.0 μg/ml,MIC90 was 4 μg/ml,levofloxacin against 30 strains of MRSA in the MIC range of 16 -256 μg/ml,MIC90for the 256 μg/ml,lrifampicin level of the 30 MRSA the MIC range of 8 -256 μg/ml,MIC90 for the 256 μg/ml,and gentamicin against 30 strains of MRSA in the MIC range of 128 - 1024 μg/ml,MIC90was 1024 μg/ml.Linezolid combined with levofloxacin MIC90 reduced to 2 μg/ml,linezolid and rifampicin combined with MIC90 reduced to 1 μg/ml,linezolid combined with gentamicin MIC90reduced to 2 μg/ml.Conclusions Linezolid has high sensitivity of the MRSA,linezolid and rifampicin in combination with synergistic based,combination of linezolid and levofloxacin,gentamicin has synergistic and additive effects,both of no antagonism.