Applying Pharmacogenomics to Antifungal Selection and Dosing: Are We There Yet?

IF 2.3 Q3 INFECTIOUS DISEASES Current Fungal Infection Reports Pub Date : 2020-03-01 Epub Date: 2020-01-16 DOI:10.1007/s12281-020-00371-w

Matthew A Miller, Yee Ming Lee

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引用次数: 9

Abstract

Purpose of review: This review summarizes recent literature for applying pharmacogenomics to antifungal selection and dosing, providing an approach to implementing antifungal pharmacogenomics in clinical practice.

Recent findings: The Clinical Pharmacogenetics Implementation Consortium published guidelines on CYP2C19 and voriconazole, with recommendations to use alternative antifungals or adjust voriconazole dose with close therapeutic drug monitoring (TDM). Recent studies demonstrate an association between CYP2C19 phenotype and voriconazole levels, clinical outcomes, and adverse events. Additionally, CYP2C19-guided preemptive dose adjustment demonstrated benefit in two prospective studies for prophylaxis. Pharmacokinetic-pharmacodynamic modeling studies have generated proposed voriconazole treatment doses based on CYP2C19 phenotypes, with further validation studies needed.

Summary: Sufficient evidence is available for implementing CYP2C19-guided voriconazole selection and dosing among select patients at risk for invasive fungal infections. The institution needs appropriate infrastructure for pharmacogenomic testing, integration of results in the clinical decision process, with TDM confirmation of goal trough achievement, to integrate antifungal pharmacogenomics into routine clinical care.

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将药物基因组学应用于抗真菌选择和给药:我们做到了吗?

综述目的:本文综述了近年来药物基因组学在抗真菌药物选择和给药方面的研究进展，为临床应用药物基因组学治疗抗真菌药物提供了思路。最近的发现:临床药理学实施联盟发布了CYP2C19和伏立康唑的指南，建议使用替代抗真菌药物或在密切治疗药物监测(TDM)的同时调整伏立康唑剂量。最近的研究表明CYP2C19表型与伏立康唑水平、临床结果和不良事件之间存在关联。此外，cyp2c19引导的预防性剂量调整在两项前瞻性研究中显示出益处。基于CYP2C19表型的药代动力学-药效学建模研究产生了伏立康唑治疗剂量建议，需要进一步的验证研究。摘要:有足够的证据支持在有侵袭性真菌感染风险的患者中实施cyp2c19指导的伏立康唑选择和给药。该机构需要适当的药物基因组学检测基础设施，在临床决策过程中整合结果，通过实现TDM确认目标，将抗真菌药物基因组学整合到常规临床护理中。

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来源期刊

Current Fungal Infection Reports INFECTIOUS DISEASES-

CiteScore

3.10

自引率

7.10%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of fungal infections. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as advances in diagnosis, current and emerging management approaches, and genomics and pathogenesis. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. Commentaries from well-known figures in the field are also provided, and an international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research.