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30min及延长输注1、2、3、4、5h的药效学达标概率。结果:对于传统30min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、5h的给药,哌拉西林他唑巴坦4.5g q8h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2g q6h,亚胺培南0.5g q6h、1g q6h,美罗培南0.5g q6h延长输注至3h时,获得最高的CFR,分别为84.38%、78.50%、87.03%、81.53%。而头孢他啶2g q8h,哌拉西林他唑巴坦4.5g q6h,亚胺培南1g q8h,美罗培南1g q8h、2g q8h延长输注至4h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,3h或者4h可能为最佳输注时间。
AIM： To evaluate pharmacodyna- mic 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 ceftaz- idime, 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 piperacil- lin-tazobactam 4.5 g q8 h was gradually pro- longed,the highest CFR was achieved by a 5 h prolonged infusion. However, the highest CFR was achieved by 3 h prolonged infusion for dos- age 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%, respective- ly. The highest CFR was achieved by 4 h pro- longed infusion for dosage regimens of ceftazi- dime 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 a- gainst severe infection. Prolonged infusion regi- mens improve pharmacodynamic target attain- ment. 3 h or 4 h is probably optimal infusion time.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2015年第1期51-55,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
宁波市自然科学基金(2012A610231)
关键词
蒙特卡罗模拟
药效学
重症感染
延长输注
monte carlo simulation
pharma-codynamics
severe infection
prolonged infusion
