蒙特卡洛模拟评价鞘内注射万古霉素治疗耐甲氧西林金黄色葡萄球菌颅内感染的给药方案

Use of Monte Carlo simulation to estimate intrathecal injection of vancomycin dosing regimens in the treatment of intracranial infections due to MRSA after craniotomy

目的应用蒙特卡洛模拟评价万古霉素鞘内注射治疗成人开颅术后耐甲氧西林金黄色葡萄球菌(MRSA)颅内感染的给药方案。方法查阅有关成都地区万古霉素对MRSA菌株的最低抑菌浓度值(MIC)及其分布频率与中国成人开颅术后脑膜炎感染患者的群体药动学资料,Crystal Ball软件模拟5 000例次后得到相应目标获得概率(PTA)和累计反应分数(CFR)。结果当MIC值分别为0.03、0.06、0.12、0.25、0.50、1、2 mg·L^(-1)时,万古霉素对MRSA的MIC分布频率分别为12.79%、12.79%、12.79%、12.79%、12.79%、29.07%和6.98%。当MIC分别为≤0.25、0.05、1、2 mg·L^(-1)时,分别予2.5、5、10、20 mg·d-1即可达到满意的抗菌活性(PTA=100%);鞘内注射10 mg·d-1的给药方案,其CFR大于90%。结论结合各MIC分布频率与达满意抗菌活性的最低剂量可知,大多数成人开颅术后MRSA颅内感染的患者鞘内注射万古霉素10 mg·d-1时均可达到满意的治疗效果,经验性鞘内注射万古霉素时可考虑10 mg·d-1的给药剂量方案。

Objective To estimate intrathecal injection of vancomycin dosing regimens in the treatment of intracranial infections due to methicillin-resistant Staphylococcus aureus(MRSA) after craniotomy using Monte Carlo simulation.Methods The minimal inhibitory concentration(MIC) distribution for vancomycin against MRSA in Chengdu and the population pharmacokinetic data of vancomycin in adult Chinese patients with post-craniotomy meningitis reported previously were collected.Five thousand times Monte Carlo simulation were conducted to obtain probability of target attainment(PTA) and cumulative fractions of response(CFR) by using Crystal Ball software.Results The MIC distribution frequency of vancomycin against MRSA was 12.79% for 0.03,0.06,0.12,0.25 and0.50 mg·L^(-1),29.07% for 1 mg·L^(-1),and 6.98% for 2 mg·L^(-1),respectively.If MIC was lower than or equal to 0.25,0.05,1 and2 mg·L^(-1),the lowest dose of vancomycin with satisfactory antibacterial activity(PTA = 100%) was 2.5,5,10 and 20 mg·d-1,respectively.The CFR of 10 mg·d-1 intrathecal injection of vancomycin was higher than 90%.Conclusions The regimen of 10 mg·d-1 of intrathecal injection of vancomycin is sufficient to achieve target levels in most adult Chinese patients with intracranial infections due to MRSA after craniotomy.Empiric regimen of 10 mg·d-1 of intrathecal injection of vancomycin could be considered for those patients.