应用蒙特卡罗模拟法评价不同MRSA感染人群利奈唑胺给药方案  

Use of Monte Carlo simulation to optimize linezolid dosing regimens in MRSA-infected patients

作　　者：刘晓东[1] 于丹[1] 张智洁[2] 马喆[1] 肇丽梅[1] 

机构地区：[1]中国医科大学附属盛京医院药学部,沈阳110004 [2]中国医科大学附属盛京医院检验科,沈阳110004

出　　处：《实用药物与临床》2013年第10期931-933,共3页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省教育厅2010年立项课题(L2010578)

摘　　要：目的 依据抗菌药物的PK/PD原理,运用蒙特卡罗模拟法对国内外健康人群及肾功能不全患者应用利奈唑胺的给药方案进行评价.方法 测定我院2013年1-3月144株甲氧西林耐药金黄色葡萄球菌（MRSA）的最低抑菌浓度（MIC）,收集国内外已发表的利奈唑胺的药代动力学资料,利用Crystal Ball软件模拟5 000例患者的目标获得概率（PTA）和累计反应分数（CFR）.结果 对于国外健康人群,当MIC=1时,PTA〉90%;当MIC=2或4时,PTA〈90%.对于国内健康人群,PTA均〈90%.对于国外肾功能不全患者,当肌酐清除率在40~80、10~39 mL/min,PTA均〈90%;对于肌酐清除率〈10 mL/min的患者,当MIC=1时,PTA〉90%,当MIC=2或4时,PTA〈90%.对于国内重症感染患者,当MIC=1时,PTA〉90%;当MIC=2或4时,PTA〈90%.各群体的CFR均〈90%.结论 当MIC=1时,国外健康人群、国内重症感染患者及肌酐清除率〈10 mL/min的患者,给予利奈唑胺600 mg q12h的剂量可达到满意的抗菌活性;而国内健康人群及肌酐清除率在10~39、40~80 mL/min的患者则达不到满意的抗菌活性,应考虑联合用药.Objective To optimize linezolid dosing regimens in MRSA-infected patients using Monte Carlo simulation according to PK/PD theory for antibiotics. Methods To Determine the strains of methicillin resistant staphylococcus aureus （MRSA） minimum bacteriostatic concentration （MIC） in our hospital from January to March 2013. The population pharmacokinetic data of linezolid reported previously were collected. The PTA and CFR of 5 000 patients were simulated using Crystal Ball software. Results For foreign healthy people, when the MIC = 1, PTA 〉 90% , when the MIC = 2 or 4, PTA 〈 90 % ; For domestic healthy people, PTA 〈 90% ; For foreign creatinine clearance in 40 - 80/10 -39 mL/min,the PTA was less than 90%. For foreign creatinine clearance 〈 10 mL/min,when the MIC = 1, PTA 〉 90% , when the MIC = 2 or 4, PTA 〈 90% ; The CFR were 〈 90% in all groups. Conclusion When the MIC = 1, foreign and domestic healthy people and creatinine clearance 〈 10 mL/min patients, give the dose of 600 mg ql2h can achieve satisfactory antimicrobial activity ;domestic healthy people and creatinine clearance in 10 -39/40 N 80 mL/ min can not reach satisfactory antimicrobial activity, and should consider drug combination. Monte carlo simulation can predict the best dosage regimen, and improve the clinical therapeutic effect.

关 键 词：蒙特卡罗模拟法 利奈唑胺 甲氧西林耐药金黄色葡萄球菌 

分 类 号：R515[医药卫生—内科学]