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万古霉素的给药、监测及毒性:临床实践的批判性综述

Vancomycin dosing, monitoring and toxicity: Critical review of the clinical practice.

作者信息

Zamoner Welder, Prado Iara Ranona Sousa, Balbi André Luis, Ponce Daniela

机构信息

Botucatu School of Medicine, University São Paulo State-UNESP, Botucatu, Brazil.

Bauru School of Medicine - USP, University of São Paulo, Bauru, Brazil.

出版信息

Clin Exp Pharmacol Physiol. 2019 Apr;46(4):292-301. doi: 10.1111/1440-1681.13066. Epub 2019 Feb 19.

Abstract

Vancomycin is an antibiotic used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis may lead to multiple organ failure; it is considered a risk factor for the development of acute kidney injury (AKI), with an overall mortality rate of around 45%, which can reach the surprising rate of 70% with the combination of AKI and sepsis. Considering the high mortality rate of sepsis and its related costs of hospitalization and treatment, specific measures should be adopted, such as early-goal treatment protocols: proper and early administration of antimicrobials, fluids, vasoactive drugs and transfusion support. Besides the careful selection of the antimicrobial, another concern related to critically ill patients is the proper dose of the antimicrobial, since pharmacokinetic changes are observed due to drug absorption, distribution, metabolism and elimination. Gram-positive pathogens are very common in hospitalized patients with septic shock, so vancomycin has been the antimicrobial of choice for more than 60 years. However, discussions about its dosage, administration and monitoring are extremely important, considering the risk of nephrotoxicity and the emergence of resistant S. aureus. This narrative review aims to discuss controversial aspects related to the efficacy and safety of vancomycin, correlating them with data available in the literature and identifying knowledge gaps in guide future lines of research.

摘要

万古霉素是一种抗生素,用于治疗由多重耐药革兰氏阳性菌引起的感染,尤其是耐甲氧西林金黄色葡萄球菌感染。在过去几十年中,由于败血症和感染性休克的发病率不断上升,万古霉素已在医院环境中广泛使用。败血症可能导致多器官功能衰竭;它被认为是急性肾损伤(AKI)发生的一个危险因素,总体死亡率约为45%,若AKI与败血症并发,死亡率可高达惊人的70%。鉴于败血症的高死亡率及其相关的住院和治疗费用,应采取具体措施,如早期目标治疗方案:正确且早期使用抗菌药物、液体、血管活性药物和输血支持。除了谨慎选择抗菌药物外,与重症患者相关的另一个问题是抗菌药物的合适剂量,因为由于药物的吸收、分布、代谢和排泄会观察到药代动力学变化。革兰氏阳性病原体在感染性休克的住院患者中非常常见,因此60多年来万古霉素一直是首选的抗菌药物。然而,考虑到肾毒性风险和耐甲氧西林金黄色葡萄球菌的出现,关于其剂量、给药和监测的讨论极其重要。本叙述性综述旨在讨论与万古霉素疗效和安全性相关的争议性方面,将它们与文献中的现有数据相关联,并识别知识空白以指导未来的研究方向。

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