目的 依据药动/药效(PK/PD)原理,应用蒙特卡洛模拟评价及优化头孢类抗菌药物的给药方案。方法 将临床常用静脉滴注头孢类药物头孢拉定、头孢呋辛、头孢曲松、头孢吡肟0.75 g qid、 1 g qid、2 g bid 、2 g tid 4种给药方案分别对大肠埃希菌、阴沟肠杆菌、肺炎克雷白杆菌、鲍曼不动杆菌、枸橼酸杆菌、金黄色葡萄球菌、肺炎链球菌、铜绿假单胞菌进行最低抑菌浓度(MIC)测定及蒙特卡洛模拟,评价各给药方案疗效。结果 头孢拉定、头孢呋辛的耐药率较高(47.31%~100%),累计反应分数(CFR)均小于90%;头孢呋辛对大肠埃希菌、肺炎克雷白杆菌、枸橼酸杆菌及肺炎链球菌均有可取的给药方案;头孢吡肟对8种菌株均有至少1种给药方案的CFR大于90%,并且符合时间依赖性药物特点。结论 对于治疗病菌感染,在选用头孢类药物时应遵从抗生素使用原则。目标治疗应进行致病菌株药敏试验,根据MIC值模拟相应的给药方案,实现个体化给药。
Abstract
OBJECTIVE To evaluate and optimize the treatment regimen of cephalosporins based on Monte Carlo simulation and the pharmacokinetics/pharmacodynamics (PK/PD) model.METHODS The treatment regimens of cefradine, cefuroxime, ceftriaxone and cefepime are 0.75 g qid, 1 g qid, 2 g bid and 2 g tid. And a total of 903 strains from eight species were collected. The minimum inhibitory concentration (MIC) was measured by trace broth dilution method. Monte Carlo simulation was used to simulate the regimens against Escherichia coli, Bacillus, Klebsiella pneumoniae, Acinetobacter baumannii, Citrobacter, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa. Then,the cumulative fraction of response (CFR) was calculated.RESULTS Cefhradine and cefuroximes′ rates of resistance were higher (47.31%-100%), the cumulative reaction scores(CFR) were all less than 90%. Cefuroxime has desirable regimen for Escherichia coli, Klebsiella pneumoniae, Citrobacter and Streptococcus pneumoniae. Cefepime has at least one dose regimen′s CFR for more than 90%, and cephalosporins is consistent with time-dependent drug characteristics.CONCLUSION For the treatment of infectious diseases, the choice of cephalosporins should be used to follow the principles of antibiotics. Target therapy should be used to test the pathogen susceptibility test, according to the value of MIC to simulate the corresponding dosing regimen, to achieve individualized administration.
关键词
头孢类抗菌药 /
药动/药效 /
蒙特卡洛模拟
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Key words
cephalosporins antibiotic /
pharmacokinetics/pharmacodynamics /
Monte Carlo simulation
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中图分类号：
R969.3
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参考文献
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脚注
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基金
河南省科技厅攻关项目资助(162102310540)
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