4种β-内酰胺类抗生素延长输注对重症感染的药效学研究

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (1): 51-55.

4种β-内酰胺类抗生素延长输注对重症感染的药效学研究

叶龙强¹, 石林惠¹, 裘晓蕙², 金雨虹¹, 蔡挺³

¹宁波市医疗中心李惠利医院重症医学科,宁波 315040,浙江;
²宁波市医疗中心李惠利医院肾内科,宁波 315040,浙江;
³宁波市第二医院呼吸内科,宁波 315010,浙江

收稿日期:2014-04-21 修回日期:2014-08-08 发布日期:2020-07-20
作者简介:叶龙强,男,硕士,主治医师,研究方向:重症感染与优化给药。Tel:13567480636 E-mail:longqiangy@126.com
基金资助:
宁波市自然科学基金(2012A610231)

Pharmacodynamics of prolonged dosing regimens of four β-lactam antibiotics against severe infection

YE Long-qiang¹, SHI Lin-hui¹, QIU Xiao-hui², JIN Yu-hong¹, CAI Ting³

¹Department of Intensive Care Unit, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, Zhejiang, China;
²Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, Zhejiang, China;
³Department of Respiration, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China

Received:2014-04-21 Revised:2014-08-08 Published:2020-07-20

摘要/Abstract

摘要： 目的: 评价4种β-内酰胺类抗生素延长输注给药方案对重症感染的药效学。方法: 测定医院明确为重症感染的120株革兰阴性杆菌的MIC,应用 10 000 例蒙特卡罗模拟分析头孢他啶、哌拉西林他唑巴坦、亚胺培南及美罗培南传统输注 30 min 及延长输注1、2、3、4、5 h 的药效学达标概率。结果: 对于传统30 min输注方案,没有一种抗生素能获得90%以上的累积反应分数(CFR)。缩短给药间隔、增加每次给药剂量、延长输注时间均能增加CFR。对于4种抗生素延长输注1、2、3、4、5 h 的给药,哌拉西林他唑巴坦 4.5 g q8 h的给药方案随着输注时间延长,获得的CFR相应逐渐增加。头孢他啶 2 g q6 h,亚胺培南 0.5 g q6 h、1 g q6 h,美罗培南 0.5 g q6 h延长输注至 3 h 时,获得最高的CFR,分别为 84.38%、78.50%、87.03%、81.53%。而头孢他啶 2 g q8 h,哌拉西林他唑巴坦 4.5 g q6 h,亚胺培南 1 g q8 h,美罗培南 1 g q8 h、2 g q8 h延长输注至4 h时,获得最高的CFR,分别为 83.12%、89.94%、83.87%、82.29%、86.98%。结论: 由于重症感染的耐药率较高,常规给药方案不能获得理想的药效学。延长输注时间能增加药效学达标概率,3 h 或者 4 h 可能为最佳输注时间。

关键词: 蒙特卡罗模拟, 药效学, 重症感染, 延长输注

Abstract: AIM: To evaluate pharmacodynamic profiling of dosage regimens of four β-lactam antibiotics against severe infection. METHODS: Minimum inhibitory concentrations for 120 Gram-negative bacteria from patients managed in intensive care unit were determined. A 10 000-subject Monte Carlo simulation was performed to calculate pharmacodynamic target attainment for traditional infusion and prolonged dosing regimens of 1,2,3,4 h and 5 h infusion of ceftazidime,piperacillin-tazobactam,imipenem and meropenem. RESULTS: No regimen of traditional infusion achieved cumulative fraction of response (CFR) of greater than 90%.Increasing doses,increasing frequencies and prolonging infusion time regimens achieved higher CFR.The results of prolonged infusion of 1,2,3,4 h and 5 h were as follows. When the infusion time of piperacillin-tazobactam 4.5 g q8 h was gradually prolonged,the highest CFR was achieved by a 5 h prolonged infusion. However, the highest CFR was achieved by 3 h prolonged infusion for dosage regimens of ceftazidime 2 g q6 h,imipenem 0.5 g q6 h,1 g q6 h and meropenem 0.5 g q6 h, 84.38%,78.50%,87.03%,81.53%,respectively.The highest CFR was achieved by 4 h prolonged infusion for dosage regimens of ceftazidime 2 g q8 h,piperacillin-tazobactam 4.5 g q6 h,imipenem 1 g q8 h and meropenem 1 g q8 h、2 g q8 h, 83.12%,89.94%,83.87%,82.29%,86.98%,respectively. CONCLUSION: As a result of high resistance rate in intensive care unit, no regimen attains optimal bactericidal exposure against severe infection. Prolonged infusion regimens improve pharmacodynamic target attainment.3 h or 4 h is probably optimal infusion time.

Key words: monte carlo simulation, pharmacodynamics, severe infection, prolonged infusion

中图分类号:

R978.1⁺1

叶龙强, 石林惠, 裘晓蕙, 金雨虹, 蔡挺. 4种β-内酰胺类抗生素延长输注对重症感染的药效学研究[J]. 中国临床药理学与治疗学, 2015, 20(1): 51-55.

YE Long-qiang, SHI Lin-hui, QIU Xiao-hui, JIN Yu-hong, CAI Ting. Pharmacodynamics of prolonged dosing regimens of four β-lactam antibiotics against severe infection[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(1): 51-55.

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