地产化注射用头孢唑林钠对葡萄球菌体外PK/PD研究  

In vitro pharmacokinetic/pharmacodynamic studies on localized cefazolin sodium for injection against staphylococci

作　　者：杜梦娇 王雪婷 肖永红 Du Mengjiao;Wang Xueting;Xiao Yonghong(Shandong First Medical University&Shandong Academy of Medical Sciences,Ji'nan 250117;Jinan Microecological Biomedicine Shandong Laboratory,Ji'nan 250098;Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,the First Hospital of Zhejiang University School of Medicine,Hangzhou 310003;Research Units of Infectious disease and Microecology,Chinese Academy of Medical Sciences,Hangzhou 310003)

机构地区：[1]山东第一医科大学(山东省医学科学院),济南250117 [2]济南微生态生物医学山东省实验室,济南250098 [3]浙江大学医学院附属第一医院传染病重症诊治全国重点实验室、国家感染性疾病临床医学研究中心、国家传染病医学中心、感染性疾病诊治协同创新中心,杭州310003 [4]中国医学科学院感染病及微生态研究创新单元,杭州310003

出　　处：《中国抗生素杂志》2024年第9期1075-1080,I0001,共7页Chinese Journal of Antibiotics

摘　　要：目的研究地产化注射用头孢唑林钠对葡萄球菌的体外抗菌效果,为临床用药提供参考。方法通过药敏实验、杀菌曲线和体外药动学/药效学(pharmacokinetics/pharmacodynamics,PK/PD)模型比较地产化与原厂头孢唑林钠体外抗菌效果。结果地产化与原厂头孢唑林钠对所测4株细菌的最低抑菌浓度(minimum inhibitory concentration,MIC)值完全一致,对金黄色葡萄球菌ATCC29213、2株临床分离甲氧西林敏感金黄色葡萄球菌(methicillin-susceptible Staphylococcus aureus,MSSA)的MIC值均为0.25μg/mL,对1株甲氧西林敏感凝固酶阴性葡萄球菌(methicillin-susceptible coagulas-negative Staphylococcus,MSCNS)MIC值均为0.06μg/mL。2种头孢唑林钠对4株葡萄球菌在3种药物浓度下的杀菌曲线无显著差异,药物浓度为1×MIC时细菌生长受到明显抑制,4株细菌24 h菌液浓度增量小于2 lgCFU/mL,药物浓度为2×MIC和4×MIC时,菌落数量均由6 lgCFU/mL持续下降到3 lgCFU/mL左右。分析动态杀菌曲线发现,2种头孢唑林钠整体PK/PD模拟结果相似,但对于菌株MSCNS117933和MSSA164342的杀菌曲线面积差,地产化头孢唑林钠参数值为(151.40±0.05)和(177.69±2.79)lgCFU·h/mL,原厂头孢唑林钠参数值为(151.10±0.11)和(170.4±1.96)lgCFU·h/mL,地产化参数值均大于原厂。结论地产化与原厂头孢唑林钠对葡萄球菌的抗菌效果整体相同。Objective To investigate the in vitro antimicrobial effects of cefazolin sodium for injection against staphylococci and provide reference for clinical medication.Methods Comparison of in vitro antimicrobial efficacy of localized and original cefazolin sodium by in vitro antibacterial susceptibility test,time-kill curve and pharmacokinetics/pharmacodynamics modeling was processed.Results The minimum inhibitory concentration(MIC)values of localized and original cefazolin sodium against staphylococci were consistent,with 0.25μg/mL against Staphylococcus aureus(S.aureus)ATCC29213 and 2 clinical strains of methicillin-sensitive S.aureus(MSSA),and 0.06μg/mL against 1 strain of methicillin-sensitive coagulase-negative Staphylococcus(MSCNS).There was no significant difference in the time-kill curve of the 2 types of cefazolin sodium against the 4 strains of S.aureus at 3 drug concentrations.Bacteria was significantly inhibited at the drug concentration of 1×MIC,and the total number of colonies of 4 strains increased by less than 2 lgCFU/mL in 24 h.The number of colonies gradually decreased from 6 lgCFU/mL to about 3 lgCFU/mL at the 2×MIC and 4×MIC drug concentrations.Overall,the PK/PD results of the 2 agents were similar by analyzing the dynamic sterilization curves,but the area difference of the bactericidal curves of localized cefazolin sodium against MSCNS117933 and MSSA164342 were greater than those of the original cefazolin sodium.The parameter values of the original cefazolin sodium were(151.40±0.05)and(177.69±2.79)lgCFU·h/mL,and the localized cefazolin sodium were(151.10±0.11)and(170.4±1.96)lgCFU·h/mL,respectively.Conclusion The antibacterial effect of localized cefazolin sodium against staphylococci is the same as that of original cefazolin sodium.

关 键 词：头孢唑林钠 药动学/药效学 地产化 葡萄球菌 杀菌曲线 体外 

分 类 号：R978.1[医药卫生—药品]