头孢比罗与万古霉素、利奈唑胺、达托霉素对血流感染葡萄球菌的体外药效学比较  

In vitro pharmacodynamic study of ceftobiprole,vancomycin,linezolid and daptomycin against staphylococcal bloodstream infections

作　　者：李玲琴 喻玮[1] 嵇金如 刘志盈 肖永红[1] Li Lingqin;Yu Wei;Ji Jinru;Liu Zhiying;Xiao Yonghong(State Key Laboratory for Diagnosis and Treatment of Infectious Disease,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;the Infectious Department,Taizhou Municipal Hospital,Taizhou 318000,China)

机构地区：[1]浙江大学医学院附属第一医院传染病诊治国家重点实验室,杭州310003 [2]台州市立医院感染科,台州318000

出　　处：《中华传染病杂志》2023年第12期773-780,共8页Chinese Journal of Infectious Diseases

基　　金：中央高校基本科研业务费专项资金(2022ZFJH03);浙江省重点研发计划(2021C03068)。

摘　　要：目的分析头孢比罗、万古霉素、利奈唑胺、达托霉素对血流感染金黄色葡萄球菌(SAU)和凝固酶阴性葡萄球菌(CNS)的体外药效,并评价各给药方案的抗菌效果,为临床用药提供依据。方法全国血流感染细菌耐药监测联盟收集了2021年1月至12月来自我国51家医院血培养的葡萄球菌共1777株,采用稀释法测定头孢比罗、万古霉素、利奈唑胺、达托霉素对葡萄球菌的最低抑菌浓度(MIC);通过蒙特卡罗模拟(MCS)预测4种药物不同给药方案的目标获得概率(PTA)和累积达标率(CFR)。结果头孢比罗对耐甲氧西林金黄色葡萄球菌(MRSA)表现出较强的抗菌活性,MIC50(抑制50%细菌的MIC值)、MIC90(抑制90%细菌的MIC值)分别为0.500、1.000 mg/L,MIC范围为≤0.060~4.000 mg/L;对SAU和CNS的耐药率分别为0.1%(1/1073)和7.7%(54/704)。万古霉素、达托霉素未检测到葡萄球菌耐药。4种药物对甲氧西林敏感金黄色葡萄球菌(MSSA)均未见耐药。MCS发现,标准给药方案头孢比罗500 mg(每8 h 1次)、达托霉素6 mg·kg-1·d-1对葡萄球菌均可达到较高的PTA和CFR;万古霉素、利奈唑胺的标准给药方案对葡萄球菌均CFR低。万古霉素1000 mg(每8 h 1次)给药时,MRSA、MSSA的CFR均≥90.0%,而CNS的CFR仍<80.0%。利奈唑胺600 mg(每8 h 1次)给药时,对葡萄球菌的CFR均≥90.0%。结论头孢比罗、万古霉素、利奈唑胺、达托霉素对葡萄球菌均有较强的抗菌活性。头孢比罗、达托霉素标准给药方案可达到有效的抗菌效果,万古霉素、利奈唑胺有必要根据MIC及菌种适当增加用药剂量。Objective To evaluate the antibacterial efficacy of ceftobiprole,vancomycin,linezolid,and daptomycin against Staphylococcus aureus(SAU)and coagulase-negative Staphylococcus(CNS)bloodstream infections,which can provide a reference for clinical medication.Methods A total of 1777 strains of staphylococci were isolated from blood culture of 51 hospitals within the Blood Bacterial Resistant Investigation Collaborative System(BRICS)from January to December in 2021.The dilution method was used to assess the minimum inhibitory concentrations(MIC)of ceftobiprole,vancomycin,linezolid and daptomycin on staphylococci.Additionally,the probability of target attainment(PTA)and cumulative fraction of response(CFR)of these medications in varied dosage regimens were predicted using Monte Carlo simulation.Results Ceftobiprole demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus(MRSA),the MIC50 and MIC90 were 0.500 and 1.000 mg/L,respectively,and the MIC range was≤0.060 to 4.000 mg/L.Meanwhile,the ceftobiprole-resistance rate of SAU was 0.1%(1/1073),but the resistance rate of CNS was 7.7%(54/704).There was no evidence of staphylococcal resistance to daptomycin or vancomycin.Against methicillin-sensitive Staphylococcus aureus(MSSA),no resistance to the four drugs was observed.Monte Carlo simulation showed that standard drug regimens of ceftobiprole(500 mg once every eight hours)and daptomycin(6 mg·kg-1·d-1)achieved high PTA and CFR against staphylococcus.The current vancomycin and linezolid standard treatment for staphylococcal bloodstream infections had a low CFR.When vancomycin 1000 mg once every eight hours was used,the CFRs of MRSA and MSSA were both≥90.0%,while the CFR of CNS was still less than 80.0%.CFR of linezolid against staphylococcus was≥90.0%under the dosages of 600 mg once every eight hours.Conclusions Ceftobiprole,vancomycin,linezolid and daptomycin all show strong antibacterial activity against staphylococcus.Ceftobiprole and daptomycin standard treatment represen

关 键 词：万古霉素 利奈唑胺 达托霉素 头孢比罗 血流感染 葡萄球菌 体外药效学 蒙特卡洛模拟 

分 类 号：R969[医药卫生—药理学]