抗菌药物治疗链球菌的蒙特卡洛模拟研究

Monte Carlo simulation study on antimicrobial agents for the treatment of Streptococcus

摘要:

目的 借助全国血流感染耐药监测联盟（BRICS）平台收集的链球菌属细菌，评价头孢曲松、左氧氟沙星及莫西沙星给药方案，以期为临床医生合理用药提供依据。 方法 采用琼脂稀释法测定头孢曲松、左氧氟沙星及莫西沙星药物敏感情况，应用蒙特卡洛模拟方法研究三种药物不同给药方案的达标概率和累计反应分数（CFR）。 结果 最低抑菌浓度（MIC）检测结果显示，头孢曲松、左氧氟沙星和莫西沙星对肺炎链球菌的敏感率分别为82.22%、97.78%、97.78%，对其他链球菌的敏感率分别为97.66%、80.14%、81.07%。蒙特卡洛模拟结果显示，头孢曲松以1、2 g/24 h剂量治疗链球菌属细菌感染，获得的CFR均≥ 90%。左氧氟沙星以750 mg/24 h剂量治疗其他链球菌感染，获得的CFR为93%；左氧氟沙星500 mg/24 h剂量治疗链球菌属细菌感染，获得的CFR值< 90%。莫西沙星以400、800 mg/24 h剂量给药治疗其他链球菌感染，获得的CFR均>90%，治疗肺炎链球菌感染获得的CFR均 < 90%。 结论 采用头孢曲松、左氧氟沙星和莫西沙星治疗链球菌引起的血流感染时，头孢曲松对其MIC值不同时必须选择不同给药剂量才能进行有效治疗，左氧氟沙星以750 mg/24 h给药疗效明显高于以500 mg/24 h给药，若莫西沙星对链球菌属细菌MIC值不在敏感范围内，则不建议用于其感染的治疗。

Abstract:

Objective To evaluate the administration scheme of ceftriaxone, levofloxacin and moxifloxacin based on Streptococcus spp. collected by national blood infection Bacterial Resistant Investigation Collaborative System (BRICS), provide basis for clinicians to use antimicrobial agents rationally. Methods Antimicrobial susceptibility of ceftriaxone, levofloxacin and moxifloxacin was determined by agar dilution method, probability of target attainment (PTA)and cumulative fraction of response (CFR)of different administration schemes of three antimicrobial agents was studied with Monte Carlo simulation method. Results Minimum inhibitory concentration (MIC) detection result showed that the susceptibility rates of ceftriaxone, levofloxacin and moxifloxacin to Streptococcus pneumoniae were 82.22%, 97.78% and 97.78% respectively, to other Streptococcus were 97.66%, 80.14% and 81.07% respectively. Monte Carlo simulation result showed that CFR were both ≥ 90% when ceftriaxone was used to treat streptococcus spp. infection at doses of 1 g/24 hour and 2 g/24 hour; CFR was 93% when levofloxacin was used to treat other streptococcal infection at dose of 750 mg/24 hour; CFR was < 90% when levofloxacin was used to treat Streptococcal spp. infection at dose of 500 mg/24 hour; CFR was both >90% when moxifloxacin was used to treat other streptococcal infection at doses of 400 mg/24 hour and 800 mg/24 hour, CFR was both < 90% when moxifloxacin was used to treat Streptococcus pneumoniae. Conclusion When ceftriaxone, levofloxacin and moxifloxacin are used to treat bloodstream infection caused by Streptococcus, different dosage of ceftriaxone should be selected for effective treatment according to different MIC value, therapeutic effect of levofloxacin at 750 mg/24 hours is significantly better than that at 500 mg/24 hours, moxifloxacin is not recommended for the treatment of Streptococcus spp. infection if MIC value is not within the susceptible range.