Stewart Jackson J, Jorgensen Sarah Cj, Dresser Linda, Lau Tim Ty, Gin Alfred, Thirion Daniel Jg, Nishi Cesilia, Dalton Bruce
Pharmacy Department, Alberta Health Services, Edmonton, Alberta, Canada.
Pharmacy Department, Mount Sinai Hospital, Toronto, Ontario, Canada.
J Assoc Med Microbiol Infect Dis Can. 2021 May 3;6(1):3-9. doi: 10.3138/jammi-2020-0028. eCollection 2021 Mar.
A revised consensus guideline on therapeutic drug monitoring (TDM) of vancomycin for serious methicillin-resistant (MRSA) infections was recently published with endorsement of numerous American pharmacy and medical societies. Changing practice from trough TDM to area-under-the-curve-(AUC)-guided dosing was suggested.
Recent literature was critically appraised to determine whether AUC TDM is appropriate for Canadian hospital practice.
Previous 2009 vancomycin consensus guidelines recommended trough levels of 15-20 mg/L for serious MRSA infections, based on relatively poor evidence for efficacy or safety. In the past decade, aggressive trough targets have led to unnecessary toxicity. Adoption of a TDM strategy using an alternative parameter (AUC) has been suggested, although the evidence for any outcome benefits is low quality. In addition, implementation would require greater resources at health care institutions in the forms of more frequent serum levels or acquisition of costly Bayesian software programs. Most studies on this subject have been observational and retrospective; therefore, relationships between TDM parameters and outcomes have not been convincingly and consistently demonstrated to be causal in nature. Despite claims to the contrary, based on few experiments, available clinical data suggest correlation of trough levels and AUC is high. TDM with lower target trough levels is a simpler solution to reduce risk of toxicity.
There are serious concerns with adoption of AUC TDM of vancomycin into routine practice in Canada. Trough-based monitoring with modest reduction in target levels remains the most evidence-informed practice at this time.
一项关于万古霉素治疗严重耐甲氧西林金黄色葡萄球菌(MRSA)感染的治疗药物监测(TDM)的修订共识指南最近发布,并得到了众多美国药学和医学协会的认可。建议将实践从谷浓度TDM改为曲线下面积(AUC)指导的给药方式。
对近期文献进行严格评估,以确定AUC TDM是否适用于加拿大医院的实践。
2009年以前的万古霉素共识指南基于相对较差的疗效或安全性证据,推荐严重MRSA感染的谷浓度为15 - 20mg/L。在过去十年中,激进的谷浓度目标导致了不必要的毒性。尽管有任何结果益处的证据质量较低,但已有人建议采用使用替代参数(AUC)的TDM策略。此外,实施将需要医疗机构以更频繁的血清水平或购置昂贵的贝叶斯软件程序的形式投入更多资源。关于这个主题的大多数研究都是观察性和回顾性的;因此,TDM参数与结果之间的关系尚未令人信服且一致地证明具有因果性质。尽管有相反的说法,但基于少数实验,现有的临床数据表明谷浓度与AUC的相关性很高。采用较低目标谷浓度的TDM是降低毒性风险的更简单解决方案。
在加拿大将万古霉素的AUC TDM纳入常规实践存在严重问题。目前,基于谷浓度的监测并适度降低目标水平仍然是最有循证依据的做法。