肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义

Evaluation on the clinical significance of introduction of cefepime breakpoint for Enterobacteriaceaeinto description of susceptible-dose dependence

目的评估美国临床实验室标准化研究所文件中肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感的临床意义,为合理使用抗菌药物提供参考依据。方法采用Phoenix WinNonlin 5.2和Matlab软件进行头孢吡肟药物代谢动力学模型建模和计算不同给药方案T>MIC%结果,进一步结合临床分离肠杆菌科致病菌体外药敏数据评估头孢吡肟药敏折点引入剂量依赖性敏感的临床意义。结果药物代谢动力学曲线显示,不同给药方案有不同的最高血药浓度和T>MIC%;增加单次给药剂量可显著提高最高血药浓度,单次给药1g和2g,Cmax分别为75μg/ml和150μg/ml,1g/12h方案64.68%时间血药浓度>8μg/ml、2g/12h方案81.65%时间血药浓度>8μg/ml;而缩短给药间隔则可以显著提升T>MIC%,1g/6h方案可以维持血药浓度一直>8μg/ml。结论肠杆菌科细菌对头孢吡肟药敏折点引入剂量依赖性敏感可以帮助临床医师更合理使用头孢吡肟。

OBJECTIVE To evaluate the clinical significance of the introduction of cefepime breakpoint for Enter-obacteriaceae into the description of susceptible-dose dependence （SDD） in CLSI M100-S24 .METHODS The Phoenix WinNonlin 5 .2 and the Matlab software were used to simulate the pharmacokinetic curves and calculate T〉 MIC% of cefepime under different dosing regimens respectively . The clinical microbiology data were also reviewed to further evaluate the clinical significance of the introduction of cefepime breakpoint for Enterobacteri-aceae into description of SDD .RESULTS Pharmacokinetic curves showed different dosing regimens had different Cmax and T〉MIC% .Increase of the single dose significantly elevated Cmax .At the single dose of 1 g and 2 g , Cmax was 75 μg/ml and 150 μg/ml respectively ,（plasma concentration was 〉8 μg/ml for 64 .68% of treatment duration in the 1 g/12 h regimen and was 〉8 μg/ml for 81 .65% of treatment duration in the 2 g/12 h regimen . Shorter dosing interval significantly increased T 〉 MIC% . The 1 q/6 h dosing regimen kept the plasma concentration higher than 8 μg/ml throughout the treatment duration .CONCLUSION Introduction of cefepime breakpoint for Enterobacteriaceae into description of SDD will help physicians to use cefepime more properly .