Casapao Anthony M, Lodise Thomas P, Davis Susan L, Claeys Kimberly C, Kullar Ravina, Levine Donald P, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
Antimicrob Agents Chemother. 2015;59(6):2978-85. doi: 10.1128/AAC.03970-14. Epub 2015 Mar 9.
Given the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0-24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0-24/MIC as determined by BMD of ≤600 relative to those with AUC0-24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P = 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P = 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0-24/MIC as determined by BMD of ≤600 present an increased risk of failure.
鉴于早期适当治疗至关重要，底特律医疗中心开展了一项回顾性队列研究（2002年至2013年），以评估耐甲氧西林金黄色葡萄球菌感染性心内膜炎（IE）患者第1天万古霉素暴露情况与预后之间的关联。使用ADAPT 5中的贝叶斯程序估算每位患者第1天万古霉素浓度-时间曲线下面积（AUC0-24）和24小时最低浓度（Cmin 24），该方法已证明在有限的药代动力学采样情况下能够以低偏差和高精度准确预测万古霉素暴露情况。收集初始耐甲氧西林金黄色葡萄球菌分离株，通过肉汤微量稀释法（BMD）和Etest法测定万古霉素最低抑菌浓度（MIC）。主要结局为治疗失败，定义为持续性菌血症（≥7天）或30天归因死亡率。采用分类与回归树分析（CART）确定与治疗失败概率增加相关的万古霉素暴露变量。共有139例患者符合研究标准；76.3%为右侧IE，16.5%为左侧IE，7.2%为双侧IE。根据综合定义，共有89/139例（64%）患者治疗失败。在CART分析中，与BMD测定的AUC0-24/MIC＞600的患者相比，BMD测定的AUC0-24/MIC≤600的患者治疗失败更为明显（分别为69.8%和54.7%，P = 0.073）。在逻辑回归分析中，BMD测定的AUC/MIC≤600（调整优势比为2.3；95%置信区间为1.01至5.37；P = 0.047）与治疗失败独立相关。鉴于本研究的回顾性特点，需要进一步开展前瞻性研究，但这些数据表明，BMD测定的AUC0-24/MIC≤600的患者治疗失败风险增加。
