摘要
目的:应用蒙特卡洛模拟方法评价替加环素治疗临床常见革兰阴性杆菌引起的医院获得性肺炎(HAP)、复杂腹腔感染(cIAI)以及复杂皮肤软组织感染(cSSSI)的给药方案。方法:收集2018年中国CHINET耐药性监测网相关替加环素对鲍曼不动杆菌、大肠埃希菌、肺炎克雷伯菌以及阴沟肠杆菌的最低抑菌浓度(MIC)数据,结合药动学/药效学(PK/PD)理论利用蒙特卡洛模拟,计算不同给药方案的达标概率(PTA)和累计反应分数(CFR)。结果:治疗革兰阴性菌引起的医院获得性肺炎,当MIC≤0.5μg/mL时,替加环素50 mg q12h给药剂量的PTA>90%,当MIC≥1μg/mL,100 mg q12h剂量的PTA和CFR均大于90%,当MIC≥2μg/mL,50 mg q12h、75 mg q12h和100 mg q12h给药剂量的PTA小于90%。当替加环素治疗复杂腹腔感染,MIC≤0.5μg/mL时,50 mg q12h的PTA达到目标值,当MIC=1μg/mL时,仅100 mg q12h给药剂量的PTA大于90%。对复杂皮肤软组织感染,当MIC≤0.25μg/mL时,75 mg q12h和100 mg q12h的剂量可使PTA大于90%,当MIC≥0.5μg/mL,所有给药方案的PTA和CFR均小于90%。结论:替加环素50 mg q12h的剂量更适合用于治疗HAP。当敏感菌MIC>0.5μg/mL时,替加环素治疗cIAI可能需要100mg q12h的剂量获得最佳临床疗效。替加环素治疗cSSSI,只有当MIC≤0.25μg/mL,可以选用75 mg q12h、100 mg q12h的给药方案。对大肠埃希菌引起的三种感染,替加环素50 mg q12h的给药剂量可能获得较好的临床疗效。
AIM:To evaluate the dose regimens of tegacycline for treatment of hospital-acquired pneumonia,complex abdominal infection and complex skin and soft tissue infection caused by Gramnegative bacterial infections with Monte Carlo model.METHODS:The minimum inhibitory concentrations(MICs)of tegacycline against Acinetobacter baumannii,Escherichia coli,Klebsiella pneumoniae and Enterobacter cloacae were collected from the CHINET in 2018.The target probability(PTA)and cumulative response fraction(CFR)of different regimens were calculated using Monte Carlo simulation based on PK/PD theory of tegacycline.RESULTS:In the treatments of HAP caused by gram-negative bacteria,when MIC≤0.5μg/mL,the PTA of 50 mg q12h was greater than 90%,and when MIC≥1μg/mL,PTA and CFR of 100 mg q12h were both greater than 90%,When MIC≥2μg/mL,50 mg q12h,75 mg q12h and 100 mg q12h doses of PTA were less than 90%.In the treatment of cIAI,when MIC≤0.5μg/mL,PTA of 50 mg q12h reached the target value,and when MIC=1μg/mL,PTA of 100 mg q12h was greater than 90%.For complex skin and soft tissue infection,when the MIC≤0.25μg/mL,the PTA of 75 mg q12h and 100 mg q12h was greater than 90%,and the PTA of the three administration regimen was less than 90%,when the MIC≥0.5μg/mL.CONCLUSION:The dose of 50 mg q12h is more suitable for the treatment of HAP,when MIC>0.5μg/mL,tigecycline may need 100 mg q12h to obtain the best clinical efficacy in the treatment of cIAI.For cSSSI.when MIC≤0.25μg/mL,tigecycline can be administered with 75 mg q12h and 100 mg q12h.For the three types of infections caused by Escherichia coli,the conventional dose of tigecycline may achieve clinical efficacy.
作者
武玉洁
赵程程
席庆
WU Yujie;ZHAO Chengcheng;XI Qing(Department of Pharmacy,General Hospital of Aviation,Beijing 100012,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2023年第9期1027-1033,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
关键词
替加环素
革兰阴性菌
蒙特卡洛模拟
药效学/药动学
tegacycline
gram-negative bacteria
Monte Carlo simulation
pharma-codynamics/pharmacokinetics
