Department of Pharmacy, State University of New York Upstate University Hospital, Syracuse, NY, USA.
Department of Pharmacy, State University of New York Upstate University Hospital, Syracuse, NY, USA; Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA.
Int J Antimicrob Agents. 2018 Dec;52(6):805-810. doi: 10.1016/j.ijantimicag.2018.08.024. Epub 2018 Aug 31.
Limited evidence exists evaluating pharmacokinetic thresholds for vancomycin efficacy and nephrotoxicity using non-Bayesian methods. The objective of this study was to evaluate the 24-h steady-state vancomycin area under the concentration-time curve (AUC) thresholds for efficacy and nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSA-B) after implementing two-point pharmacokinetic therapeutic drug monitoring. A single-centre, retrospective cohort study was performed including adult patients admitted between 1 June 2016 and 1 January 2018 with MRSA-B treated with vancomycin for ≥72 h. The AUC was calculated using peak and trough vancomycin serum concentrations. Clinical success was defined as defervescence and blood culture sterilisation by Day 7. Nephrotoxicity was defined as an increase in serum creatinine of >0.5 mg/dL (or ≥50%) from baseline. Classification and regression tree (CART) analyses were performed to identify AUC thresholds for efficacy and nephrotoxicity. Forty-six patients were included in the study. Clinical success and nephrotoxicity were observed in 81.8% and 13.0%, respectively. The CART-derived vancomycin AUC thresholds for clinical success and nephrotoxicity were ≥297 mg·h/L and ≥710 mg·h/L, respectively. Patients with an AUC ≥297 mg·h/L had a >2.7-fold increase in clinical success compared with those who did not (89.5% vs. 33.3%, respectively; P = 0.01), and patients with an AUC ≥710 mg·h/L had a >7-fold increase in nephrotoxicity compared with those with an AUC <710 mg·h/L (66.7% vs. 9.3%, respectively; P = 0.04). This study supports current recommendations to target vancomycin AUC values of 400-600 mg·h/L when calculated using two-point pharmacokinetics, although a wider range may exist.
使用非贝叶斯方法评估万古霉素疗效和肾毒性的药代动力学阈值的证据有限。本研究的目的是评估实施两点药代动力学治疗药物监测后耐甲氧西林金黄色葡萄球菌菌血症（MRSA-B）患者的 24 小时稳态万古霉素浓度-时间曲线下面积（AUC）阈值与疗效和肾毒性的关系。这是一项单中心、回顾性队列研究，纳入了 2016 年 6 月 1 日至 2018 年 1 月 1 日期间因 MRSA-B 接受万古霉素治疗≥72 小时的成年患者。AUC 通过万古霉素的峰浓度和谷浓度计算得出。临床疗效定义为第 7 天体温下降和血培养无菌。肾毒性定义为血清肌酐从基线升高≥0.5 mg/dL（或≥50%）。采用分类回归树（CART）分析确定疗效和肾毒性的 AUC 阈值。研究纳入了 46 例患者。临床疗效和肾毒性的发生率分别为 81.8%和 13.0%。CART 得出的万古霉素 AUC 阈值分别为 297mg·h/L 和 710mg·h/L 时，临床疗效和肾毒性的发生情况最佳。AUC≥297mg·h/L 的患者临床疗效显著高于 AUC＜297mg·h/L 的患者（89.5% vs. 33.3%；P=0.01），AUC≥710mg·h/L 的患者肾毒性发生率显著高于 AUC＜710mg·h/L 的患者（66.7% vs. 9.3%；P=0.04）。该研究支持当前建议，即使用两点药代动力学计算时，万古霉素 AUC 值目标范围为 400-600mg·h/L，但可能存在更宽的范围。
