优化抗生素联合应用的研究  

Optimization of antibiotics in combination

作　　者：张丽华[1] 王凌峰[2] 孟昭彦[3] 于庆萍[3] 高柏青[1] 巴特[2] 王晓冬[1] 马文慧[3] 李跃宇[3] 张军[2] 

机构地区：[1]内蒙古医学院第三附属医院药剂科,包头014010 [2]内蒙古医学院第三附属医院烧伤科,包头014010 [3]内蒙古医学院第三附属医院检验科,包头014010

出　　处：《中华烧伤杂志》2008年第2期93-96,共4页Chinese Journal of Burns

基　　金：内蒙古包头医药卫生基金（2006-49）

摘　　要：目的了解环丙沙星、阿米卡星与抗铜绿假单胞菌的β内酰胺类药物体外联用的抗菌活性，优化抗生素治疗方案。方法采用棋盘法设计，微量肉汤稀释法测定上述抗生素不同组合对33株临床分离的铜绿假单胞菌的最低抑菌浓度（MIC），判定联合效应，计算其药代动力学／药效学（PK／PD）参数。结果阿米卡星与头孢他啶联用主要表现为协同作用，协同比率为57．6％；环丙沙星与头孢他啶、头孢吡肟、亚胺培南／西司他丁、美罗培南联用以协同和相加作用为主。氨基糖苷类和氟喹诺酮类抗生素，在PK／PD研究中，以血药浓度峰值（Cmax）／MIC为主要参数；β内酰胺类抗生素以血药浓度超过MIC的时间（T〉MIC）为主要参数。结论抗菌药物联用后，MIC显著降低，抗菌作用明显增强。所有抗生素的联用均以协同和相加作用为主，无拮抗作用。PK／PD研究，对制定合理给药方案、提高临床疗效具有重要作用。Objective To evaluate the antibacterial activity of Ciprofloxacin ,Amikacin in combination with β-1actams against Pseudomonas aeruginosa strains in vitro,to optimize treatment regime for antibiotics on the basis of pharmacokinetics （PK）/pharmacodynamics （PD） and drug sensitivity tests. Methods With checkerboard titration method,the minimal inhibitory concentrations（ MIC ） of a combination of antibiotics in different concentrations for 33 clinically isolated Pseudomonas aeruginosa strains were determined by broth dilution. Fractional inhibitory concentrations（FIC） were calculated for judging synergic effect of antibiotics. Results The combination of Amikacin and Ceftazidime showed synergic effects （accounting for 57.6% ）. The combinations of Ciprofloxacin with Ceftazidime, Cefepime, Imipenem/Cilastatin, Meropenem showed synergic or additive effect. In the study with PK/PD, Cmax/MIC was the principal parameters for evaluation of aminoglycoside and fluoroquinolone antibiotics,while T 〉 MIC was the principal parameter to be used to evaluate β-1actams antibiotics. Conclusion When antibiotics are used in combination ,MICs can be reduced significantly and antibacterial activities are enhanced remarkably. The combination of antibiotics results mainly in synergic or additive effect,and no inhibitory effect is observed . PK/PD analysis plays an important role in planning optimal combination regime to raise clinical efficacy.

关 键 词：抗菌药 药代动力学 假单胞菌 铜绿 微生物敏感性试验 药效学 

分 类 号：R446.5[医药卫生—诊断学]