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为评价7种β-内酰胺药物对革兰阴性菌感染的给药方案,本文用药动学/药效学的蒙特卡洛模拟,获取药效学指标(f%T>MIC)的累积效应分数(CFR)。其中,亚胺培南/西司他丁、美罗培南的CFR最高,二者0.5gtid对铜绿假单胞菌的抑菌CFR分别为76.12%和80.56%,而敏感率为74.7%和78.4%,对产超广谱β-内酰胺酶(ESBLs)菌和易产头孢菌素酶(AmpC)菌株的杀菌CFR和敏感率均达100%;头孢他啶1gtid对产ESBLs肺炎克雷伯菌、哌拉西林钠/三唑巴坦钠3.375gqid对鲍曼不动杆菌的抑菌CFR(53.89%、47.59%)与敏感率(53.2%、47.5%)基本一致;增加头孢吡肟的剂量和给药次数可提高CFR值,2gtid对产气肠杆菌、枸橼酸杆菌属的杀菌CFR为92.83%、96.99%,大于敏感率(67.3%、78.8%)。因此,对产ESBLs菌和易产AmpC酶菌株,选用方案为亚胺培南/西司他丁0.5gtid或美罗培南0.5gtid;对产ESBLs大肠埃希菌,可选哌拉西林钠/三唑巴坦钠3.375gq4h;对产气肠杆菌、枸橼酸杆菌属,或选用头孢吡肟2gtid;对铜绿假单胞菌、鲍曼不动杆菌感染的经验治疗需考虑联合用药。基于PK/PD的蒙特卡洛模拟,可用以评价抗感染治疗的效果,优化给药方案设计。
To evaluate the dosing regimen of seven β-lactam drugs against Gram-negative infections, the cumulative effect score of pharmacodynamic parameters (f% T> MIC) was obtained using Monte Carlo simulation of pharmacokinetics / pharmacodynamics (CFR). Among them, imipenem / cilastatin and meropenem had the highest CFR. The inhibition rates of 0.5gtid against P. aeruginosa were 76.12% and 80.56% respectively, while the sensitivity rates were 74.7% and 78.4% The bactericidal CFR and sensitivity of ESBLs and AmpC strains were both 100%. Ceftazidime 1gtid was effective in producing ESBLs-producing Klebsiella pneumoniae, piperacillin The antibacterial CFR (53.89%, 47.59%) of sodium / tazobactam sodium 3.375gqid against Acinetobacter baumannii was basically the same as the sensitivity (53.2%, 47.5%); the dosage and times of adding cefepime When the CFR value was increased, the bactericidal CFR of 2gtid against Enterobacter aerogenes and Citrobacter was 92.83% and 96.99%, respectively, higher than the sensitivity (67.3% and 78.8%). Therefore, the production of ESBLs bacteria and easy to produce AmpC enzyme strains, options for imipenem / cilastatin 0.5gtid or meropenem 0.5gtid; ESBLs-producing Escherichia coli, optional piperacillin sodium / triazole Batan sodium 3.375gq4h; Enterobacter aerogenes, Citrobacter genus, or the choice of cefepime 2gtid; Pseudomonas aeruginosa, Acinetobacter baumannii experience in the treatment of infection should be considered in combination. Based on PK / PD Monte Carlo simulation, can be used to evaluate the effect of anti-infective therapy, drug design optimization.