Elbarbry Fawzy
School of Pharmacy, Pacific University, 222 SE 8th Ave., Hillsboro, OR, 97123, USA.
Eur J Drug Metab Pharmacokinet. 2018 Jun;43(3):259-268. doi: 10.1007/s13318-017-0456-4.
After more than six decades of its use as the mainstay antibiotic for the treatment of multidrug-resistant Gram-positive bacterial infections, dosing and monitoring of vancomycin therapy have not been optimized. The current vancomycin therapeutic guidelines recommend empiric doses of 15-20 mg/kg administered by intermittent infusion every 8-12 h in patients with normal kidney function. Additionally, the guidelines recommend trough concentration of 15-20 mg/L as a therapeutic goal for adult patients with severe infections. This review critically discusses the current guidelines considering the basic pharmacokinetics and pharmacodynamics of vancomycin and the recent published reports from clinical studies. More in-depth discussion will be focused on (1) providing evidence of advantages of administering vancomycin by continuous infusion compared to intermittent infusion; (2) revising the current practice of trough-only monitoring versus the area under concentration-time curve (AUC); and (3) assessing the current practice of weight-based dosing versus AUC-based dosing. Using the gathered information presented in this paper, two user-friendly and scientifically based dosing strategies are proposed to improve the efficiency of vancomycin dosing while avoiding the risk of nephrotoxicity and minimizing the cost of therapeutic drug monitoring.
在作为治疗多重耐药革兰氏阳性菌感染的主要抗生素使用了六十多年后,万古霉素治疗的剂量确定和监测仍未得到优化。当前的万古霉素治疗指南建议,肾功能正常的患者每8 - 12小时间歇输注经验性剂量15 - 20mg/kg。此外,该指南建议将15 - 20mg/L的谷浓度作为重症成年患者的治疗目标。本综述批判性地讨论了当前指南,同时考虑了万古霉素的基本药代动力学和药效学以及近期发表的临床研究报告。更深入的讨论将集中在:(1)提供持续输注万古霉素相比于间歇输注的优势证据;(2)修订当前仅监测谷浓度与浓度-时间曲线下面积(AUC)的做法;(3)评估当前基于体重给药与基于AUC给药的做法。利用本文收集的信息,提出了两种方便用户且基于科学的给药策略,以提高万古霉素给药效率,同时避免肾毒性风险并将治疗药物监测成本降至最低。