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目的 根据药动学/药效学(PK/PD)理论评价β-内酰胺类药物治疗大肠埃希菌(E.coli)所致的血流感染的给药方案。方法 回顾性调查医院2013年7月-2016年6月血流感染的细菌分布及耐药监测报告,按照美国临床实验室标准化协会(CLSI)2013版标准,对大肠埃希菌的最低抑菌浓度设置为离散均匀分布,确定4种抗菌药物的16种给药方案,运用PK/PD模型和蒙特卡洛模拟10000例“真实患者”的累积反应分数(CFR),优化出最佳初始给药方案。结果 哌拉西林他唑巴坦4种给药方案(3.375g,q8h;3.375g,q6h;4.5g,q8h;4.5g,q6h)、头孢他啶4种给药方案(1.0g,q12h;1.0g,q8h;2.0g,q12h;2.0g,q8h)、头孢吡肟4种给药方案(1.0g,q12h;1.0g,q8h;2.0g,q12h;2.0g,q8h)的CFR均<80%;亚胺培南西司他丁4种给药方案(0.5g,q8h;0.5g,q6h;1.0g,q8h;1.0g,q6h)中0.5g,q6h的CFR为85.30%,1.0g,q6h的CFR为92.75%,其它两种给药方案CFR<80%。结论 医院大肠埃希菌所致的血流感染的经验治疗,建议选择最佳给药方案亚胺培南西司他丁1.0g,q6h,或次佳给药方案亚胺培南西司他丁0.5g,q6h,选择联合治疗方案,目标治疗则应根据大肠埃希菌MIC值选用相应的给药方案。
OBJECTIVE: To evaluate the dosage regimen of β-lactam in the treatment of E.coli-induced bloodstream infection according to the pharmacokinetic / pharmacodynamic (PK / PD) theory. Methods The bacterial distribution and drug resistance surveillance of bloodstream infection from July 2013 to June 2016 were retrospectively reviewed. According to the CLSI 2013 edition, the minimum inhibitory concentration against Escherichia coli Sixteen dosing regimens of four antibacterials were determined by discrete and uniform distribution. The optimum initial dose was optimized by PK / PD model and Monte Carlo simulation of cumulative response fraction (CFR) of 10000 “real patients” Drug program. Results Four dosage regimens of piperacillin and tazobactam (3.375g, q8h; 3.375g, q6h; 4.5g, q8h; 4.5g, q6h) the CFRs of all the four kinds of dosing regimens of cefepime (1.0g, q12h; 1.0g, q8h; 2.0g, q12h; 2.0g, q8h) were all less than 80% 0.5g, 0.5g, q6h; 1.0g, q8h; 1.0g, q6h), the CFR of q6h was 85.30%, the CFR of 1.0g and q6h was 92.75%, the other two dosing regimens CFR <80%. Conclusion The empirical treatment of Escherichia coli-induced bloodstream infection in hospitals suggests that the best dosing regimen imipenem cilastatin 1.0g, q6h, or the second best dosing regimen imipenem cilastatin 0.5g , q6h, select the combination of treatment options, the target treatment should be based on the value of E. coli MIC selected the appropriate dosing regimen.