Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation

作者全名："Xie, Jiao; Yang, Qianting; Han, Xinyan; Dong, Yuzhu; Zhang, Tao; Li, Youjia; Ji, Meixi; Liu, Chenwei; Cai, Yan; Wang, Yan"

作者地址："[Xie, Jiao; Yang, Qianting; Li, Youjia; Ji, Meixi; Liu, Chenwei; Cai, Yan; Wang, Yan] Xi An Jiao Tong Univ, Dept Pharm, Affiliated Hosp 2, Xian, Peoples R China; [Han, Xinyan; Zhang, Tao] Xi An Jiao Tong Univ, Coll Stomatol, Dept Pharm, Xian, Peoples R China; [Dong, Yuzhu] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 3, Chongqing, Peoples R China"

通信作者："Wang, Y (通讯作者)，Xi An Jiao Tong Univ, Dept Pharm, Affiliated Hosp 2, Xian, Peoples R China."

来源：ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000800284300004

JCR分区：Q1

影响因子：4.9

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：antifungal de-escalation treatment; critically ill patients; Monte Carlo simulations; PK/PD properties

摘要："Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database (n = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Cumulative fraction of response (CFR) was calculated for each dosing regimen. Most guideline-recommended dosing regimens of fluconazole and voriconazole could achieve target exposure as de-escalation treatment in critically ill patients. For initial echinocandin treatment, achievement of the target exposure decreased as body weight increased, and the intermittent dosing strategy had a slightly higher CFR value in most simulations compared to conventional dosing strategy. For Candida albicans and Candida glabrata infection, caspofungin at the lowest dose achieved a CFR of >90%, while micafungin or anidulafungin required almost the highest doses simulated in this study to achieve the same effect. None of the echinocandins other than 150 mg every 24 h (q24h) or 200 mg q48h of caspofungin achieved the target CFR for Candida parapsilosis infection. These findings support the guideline-recommended dose of triazoles for antifungal de-escalation treatment and confirm the insufficient dosage of echinocandins in critically ill patients, indicating that a dosing regimen based on body weight or intermittent dosing of echinocandins may be required."

基金机构："National Natural Science Foundation of China [71904155, 82003860]; Key Research and Development Program of Shaanxi [2021SF-179, 2021KW-65]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (71904155 and 82003860) and the Key Research and Development Program of Shaanxi (2021SF-179 and 2021KW-65).