目的 优化儿童耐甲氧西林金黄色葡萄球菌(MRSA)感染的万古霉素的经验给药方案。方法 根据万古霉素的药代动力学/药效动力学(PK/PD)模型,对不同剂量的万古霉素的给药方案进行蒙特卡罗模拟模拟,从而得出最佳的给药方案。结果 随着万古霉素的日剂量增加,预期AUC0-24/MIC> 400的百分比亦相应增加。当MIC为0.5 mg·L-1时,万古霉素的剂量为35 mg·kg-1·d-1,AUC0-24/MIC> 400的比例即可达99.41%。当MIC为1 mg·L-1时,剂量增加至65 mg·kg-1·d-1时, AUC0-24/MIC> 400才能达到 97.55%。当MIC为2 mg·L-1及以上时,没有剂量能达到AUC0-24/MIC>400的要求。结论 儿童MRSA感染时,当MIC为0.5 mg·L-1时,万古霉素的经验治疗剂量应大于35 mg·kg-1·d-1;当MIC为1.0 mg·L-1时,推荐剂量应大于65 mg·kg-1·d-1。
Abstract
OBJECTIVE To optimize vancomycin regimen in children with MRSA infection. METHODS Vancomycin AUC0-24/MIC predictions were performed across a range of dosages (20-70 mg·kg-1·d-1) using a Monte Carlo simulation (n=10 000). AUC0-24 was calculated as daily dose divided by vancomycin clearance, and daily dose was fixed for a given simulation. The MIC distribution for MRSA was obtained from the RESULTS of clinical laboratory, the First Affiliated Hospital of Guangxi Medical University, from 2012 to 2014 (n=430;30%≤0.5 mg·L-1; 58.6%= 12 mg·L-1; and 11.2%=2 mg·L-1; 0.2%=4 mg·L-1). RESULTS With increasing vancomycin daily dose, the percentage of patients predicted to achieve AUC0-24/MIC >400 similarly increased. At 35 mg·kg-1·d-1, the percentage predicted to achieve AUC0-24/MIC >400 was 99.41% when MIC was 0.5 mg·L-1. However, the dosage rose to 65 mg·kg-1·d-1 when MIC was 1 mg·L-1. At this regimen, the percentage predicted to achieve AUC0-24/MIC >400 was 97.55%. At a MIC of 2 mg·L-1 and more, none of the dosages predicted to achieve AUC0-24/MIC>400. CONCLUSION Recommended empiric vancomycin dosing in children should be above 35 mg·kg-1·d-1 when MIC is 0.5 mg·L-1. At the MIC is 1 mg·L-1, the recommended regimen should be over 65 mg·kg-1·d-1.
关键词
万古霉素 /
蒙特卡罗模拟 /
药代动力学/药效动力学 /
耐甲氧西林金黄色葡萄球菌 /
儿童
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Key words
vancomycin /
Monte Carlo simulation /
PK/PD /
MRSA /
children
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中图分类号:
R969.1
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81460569);广西卫生厅中医药科技专项(GZZJ13-17);广西高校中青年教师基础能力提升项目(KY2016YB098);广西壮族自治区卫生与计划生育委员会课题(Z2012112)
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