蒙特卡洛模拟评价和优化鲍曼不动杆菌血流感染给药方案  

Use of Monte Carlo simulation to estimate and optimize therapeutic regimens of bloodstream infections caused by Acinetobacter baumannii

作　　者：辛娜[1] 吴跃刚[2] 王馨 喻玮[3] 嵇金如 应超群 王培培 刘志盈 李卓[1] 肖永红[3] Xin Na;Wu Yue-gang;Wang Xin;Yu Wei;Ji Jin-ru;Ying Chao-qun;Wang Pei-pei;Liu Zhi-ying;Li Zhuo;Xiao Yong-hong(Department of Laboratory,the First Affiliated Hospital of Xi'an Medical University,Xi'an 710077;Department of Respiratory Medicine,Huashan Central Hospital,Xi'an 710043;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003)

机构地区：[1]西安医学院第一附属医院检验科,西安710077 [2]西安市华山中心医院呼吸内科,西安710043 [3]浙江大学医学院附属第一医院,传染病诊治国家重点实验室,国家感染性疾病临床研究中心,感染性疾病诊治协同创新中心,杭州310003

出　　处：《中国抗生素杂志》2022年第12期1285-1290,共6页Chinese Journal of Antibiotics

基　　金：浙江省重点研发计划(No.2021C03068)。

摘　　要：目的应用蒙特卡洛模拟研究头孢哌酮/舒巴坦、替加环素和多黏菌素B治疗鲍曼不动杆菌血流感染的疗效,预测和评价不同抗菌药物的抗菌效果,进而优化临床给药方案。方法借助全国血流感染细菌耐药监测联盟(BRICS)平台收集2018—2019年血流感染来源的鲍曼不动杆菌514株,使用文献公开发表的头孢哌酮/舒巴坦、替加环素和多黏菌素B的药动学参数,基于药动学/药效学(PK/PD)理论利用蒙特卡洛模拟法,计算不同给药方案在各特定的MIC值获得的目标概率,即达标概率(PTA)和累积反应分数(CFR),以PTA或CFR≥90%作为临床疗效评价的指标。结果治疗鲍曼不动杆菌引起的血流感染,头孢哌酮/舒巴坦给药方案4.5 g q6 h在最低抑菌浓度(MIC)≤1 mg/L时,可获得大于或接近90%的目标PTA值,临床分离菌的CFR值为21.53%。替加环素推荐剂量(50 mg q12 h),在MIC≤0.25 mg/L时,可获得大于90%的目标PTA值,100 mg q12 h的给药方案对临床菌株的CFR值为81.04%。多黏菌素B 1.25 mg/kg 1h输注q12 h给药方案,可使MIC≤1 mg/L的细菌的PTA达到90%以上,高剂量的多黏菌素给药方案[负荷2 mg/kg 2 h输注后2.5 mg/(kg·d)持续输注]在MIC为2 mg/L时,可提供较高的PTA(96.83%),临床CFR可达到96.26%。结论头孢哌酮/舒巴坦治疗鲍曼不动杆菌感染时,应考虑到大剂量的给药方案。同时由于鲍曼不动杆菌对头孢哌酮/舒巴坦群体耐药率较高导致CFR值较低,临床治疗中可能需要使用其他抗生素或将头孢哌酮/舒巴坦与其他抗菌药物联合使用取得更好的治疗效果。替加环素建议使用100 mg q12 h的给药方案,多黏菌素B建议使用负荷2.5 mg/kg 2 h输注后1.5 mg/kg 1 h输注q12 h或负荷2 mg/kg 2 h输注后2.5 mg/(kg·d)持续输注的给药方案。Objective To evaluate the efficacy of cefoperazone/sulbactam,tigecycline,and polymyxin B in the treatment of bloodstream infections caused by Acinetobacter baumannii by Monte Carlo simulation,and to predict and evaluate the antibacterial effects of different antibiotics,so as to optimize the clinical administration scheme.Methods A total of 514 A.baumannii strains isolated from bloodstream infections from 2018 to 2019 were collected with the help of BRICS platform.The target probability(PTA)and cumulative response score(CFR)of different dosage regimens at each specific MIC value were calculated using Monte Carlo simulation based on the published pharmacokinetic parameters of cefoperazone/sulbactam,tigecycline and polymyxin B,and PK/PD theory.PTA or CFR≥90%was used as the evaluation index of clinical efficacy.Results In the treatments of bloodstream infections caused by A.baumannii,cefoperazone/sulbactam(2:1)4.5 g q6 h achieved more than or close to 90%PTA with MIC≤1 mg/L,and the CFR value was 21.53%.Using the recommended dose of tigecycline(50 mg,q12 h),when MIC≤0.25 mg/L,more than 90%of the target PTA value could be obtained,and the CFR value of 100 mg q12 h was 81.04%.The results showed that polymyxin B(1.25 mg/kg,1 h infusion,q12 h)could make the PTA of bacteria with MIC≤1 mg/L reach more than 90%.The high dose polymyxin B[loading 2 mg/kg infused for 2 h,2.5 mg/(kg·d)continuous infusion]could provide higher PTA(96.83%)and CFR(96.26%)when MIC was 2 mg/L.Conclusion When cefoperazone/sulbactam is used in the treatment of A.baumannii infection,the high dose regimen should be considered.The higher resistance rate of A.baumannii to cefoperazone/sulbactam leads to lower CFR value.It may be appropriate to use other antibiotics or combine cefoperazone/sulbactam with other antibacterial agents in clinical treatment to achieve better therapeutic outcomes.Tigecycline is recommended to be administered with 100 mg q12 h.Polymyxin B is recommended to be administered with loading 2.5 mg/kg infused for 2 h,1.5 mg/kg i

关 键 词：鲍曼不动杆菌 蒙特卡洛模拟 达标概率 累积反应分数 

分 类 号：R9[医药卫生—药学]