一/二代头孢菌素用于肝胆外科手术预防性抗菌的效果模拟研究

Effects of the first- and second-generation cephalosporins on preventive antibacterial therapy in hepatobiliary surgery:a simulation study

目的模拟在微生物敏感性水平下一/二代头孢菌素用于肝胆外科手术预防性抗菌的效果。方法以2 g头孢唑啉和1.5 g头孢呋辛分别作为一、二代头孢菌素的考察模型,以大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌和表皮葡萄球菌为目标菌群。利用蒙特卡洛模拟,计算两药给药后6 h内给药间期游离药物浓度大于最低抑菌浓度的时间(fT>MIC)对各最低抑菌浓度(MIC)的目标获得概率(PTA),以及fT>MIC对具有累积MIC分布的各目标菌群的累积反应分数(CFR),以PTA或CFR≥90%认为效果最优。结果 2 g头孢唑啉对MIC≤2μg/mL、MIC=4μg/mL、MIC=8μg/mL和MIC=16μg/mL的分离菌,可分别在给药后6 h、5 h、3 h和1 h内达到≥90%PTA;1.5 g头孢呋辛对MIC≤0.5μg/mL、MIC=1μg/mL、MIC=2μg/mL、MIC=4μg/mL、MIC=8μg/mL和MIC=16μg/mL的分离菌,可分别在给药后6 h、5 h、4 h、3 h、2 h和1 h内达到≥90%PTA;两药均对MIC>16μg/mL的分离菌无法在给药后1 h内达到≥90%PTA。对具有累积MIC分布的各目标菌群,2 g头孢唑啉对金黄色葡萄球菌和表皮葡萄球菌分别在给药后6 h和1 h内达到≥90%CFR;1.5 g头孢呋辛对金黄色葡萄球菌和表皮葡萄球菌分别在给药后3 h和2 h内达到≥90%CFR;两药对其他目标菌群在给药后6 h内的任意时间均无法达到≥90%CFR。结论在缺乏目标菌的具体MIC报告时,基于目前的微生物敏感性水平,头孢唑啉和头孢呋辛均较宜用于以金黄色葡萄球菌为污染菌的肝胆外科手术的抗菌预防;对于历时<6 h、<3 h的手术,分别术前给予一剂头孢唑啉、头孢呋辛即可,否则术中须追加使用抗生素。两者均不宜于以肠杆菌科细菌为污染菌的肝胆外科手术预防性抗菌。

Objective To simulate the effects of the first-and second-generation cephalosporins on preventive antibacterial therapy in hepatobiliary surgery at the current level of microbiological sensitivity.Methods Two grams of cefazolin and 1.5 grams of cefuroxime were applied as the exploratory models of the first-and second-generation cephalosporins respectively,and Escherichia coli,Klebsiella pneumoniae,Staphylococcus aureus and Staphylococcus epidermidis as the targeted bacteria.Monte Carlo Simulation was employed to calculate the probability of target attainment(PTA) of the time of free medicine concentration remains over minimum inhibitory concentration during the dosing interval(fT>MIC) at various minimum inhibitory concentrations(MIC),as well as the cumulative fraction of response(CFR) of fT>MIC for various targeted bacteria with pooled MIC distribution within 6 h after administration of cefazolin and cefuroxime,with PTA or CFR ≥90% as the optimal effect.Results Two-gram cefazolin against the isolated strain of MIC ≤ 2 μg/mL,MIC=4 μg/mL,MIC=8 μg/mL and MIC=16 μg/mL achieved ≥90% PTA within 6 h,5 h,3 h and 1 h after administration,respectively;one and a half-gram cefuroxime against the isolated strain of MIC ≤0.5 μg/mL,MIC=1 μg/mL,MIC=2 μg/mL,MIC=4 μg/mL,MIC=8 μg/mL and MIC=16 μg/mL achieved ≥90% PTA within 6 h,5 h,4 h,3 h,2 h and 1 h after administration,respectively;whereas both antibiotics against the isolated strains of MIC >16 μg/mL failed to achieve ≥90% PTA within 1 h after administration.For various targeted bacteria with pooled MIC distribution,two-gram cefazolin against Staphylococcus aureus and Staphylococcus epidermidis achieved ≥90% CFR within 6 h and 1 h after administration,respectively;one and a half-gram cefuroxime against Staphylococcus aureus and Staphylococcus epidermidis achieved ≥90% CFR within 3 h and 2 h after administration,respectively;but both antibiotics against the other targeted bacterium failed to reach ≥90% CFR at any time up to 6 h after administration.Conclusion In the absence of specific MIC reports for the targeted bacteria,cefazolin and cefuroxime are suitable for antibacterial prophylaxis in hepatobiliary surgery with Staphylococcus aureus as a contaminated bacteria based on current microbial sensitivity level;a single-dose cefazolin and cefuroxime may be sufficient for the surgery lasting less than 6 h and 3 h respectively,otherwise intraoperative supplement of antibiotics is required.However,both antibiotics are not suitable for preventive antibacterial therapy in the hepatobiliary surgery with Enterobacteriaceae as a contaminating bacterium.