优化β-内酰胺类抗铜绿假单胞菌的给药方案探讨

Oplimizing dosage regimens of β-lactam antibiotics against Pseudomonas aeruginosa

目的评价5种β-内酰胺类抗生素不同的给药方案对铜绿假单胞菌的药效学。方法测定宁波市李惠利医院2008年1—6月120株铜绿假单胞菌的最低抑菌浓度（MIC），应用蒙特卡罗模拟方法分析头孢他啶、头孢吡肟、哌拉西林／三唑巴坦、亚胺培南及美罗培南的药效学。结果应用传统的给药方案，头孢他啶2g，1次／8h获得的累积反应分数（CFR）最高（84．5％），其次为头孢他啶1g，1次／8h（78．0％），哌拉西林／Z唑巴坦4．5g，1次／6h（72．6％），美罗培南1g，1次／8h（69．2％），亚胺培南1g，1次／8h（64．2％）。改变给药方法后，当美罗培南的剂量从1g，1次／8h增加到2g，1次／8h时，CFR从69．2％增加到74．4％；将输注时间由30min延长到3h，可以看到CFR的增加，哌拉西林／三唑巴坦4．5g，1次／8h增加的CFR最多，为24．1％；其次为头孢吡肟2g，1次／12h，亚胺培南0．5g，1次／8h，分别为16．6％和14．6％。结论由于铜绿假单胞菌的耐药率较高，没有一种传统给药方案能获得理想的杀菌概率，各药的CFR均小于90％。因此，可以考虑改变给药方法，如增加给药剂量、增加给药次数、延长输注时间以及联合给药等。

Objective To evaluate pharmacodynamic profiling of dosage regimens of five β-lactam antibiotics against Pseudomonas aeruginosa. Methods Minimum inhibitory concentrations for 120 Pseudomonas aeruginosa from Jan uary to June 2008 in Ningbo Lihuih hospital were determined. Monte Carlo simulation method was performed to calculate pharmacodynamic target attainment for ceftazidime, cefepime, piperacillin-tazobactam, imipenem and meropenem. Results When administered by traditional method, the highest CFR （84.5 % ） was achieved by ceftazidime 2 g every 8 hours, followed by ceftazidime 1 g every 8 hours （78.0%）, pipemcillin-tazobactam 4.5 g every 6 hours （72.6%）, meropenem 1 g every 8 hours （69.2%）, and imipenem 1 g every 8 hours （64.2%）.When the meropenem dosage was increased to 2 g every 8 hours, CFR increased to 74.4% ;when the infusion time was prolonged to 3 hours, increases of CFR were as follow：increases of piperacillin-tazobactam 4.5 g every 8 hours were 24.1% ,followed by cefepime 2 g every 12 hours and imipenem 0.5 g every 8 hours, 16.6% and 14.6%, respectively. Conclusions As a result of high resistance rate, no regimen attains optimal bactericidal exposure against Pseudomonas aeruginosa, the CFR of the five β-lactam antibiotics were below 90%. Therefore, it seems reasonable to change dosage regimens, such as increasing the dose, increasing the frequency, prolonging infusion time, as well as combination therapy.