Department of Pharmacy, Hackensack University Medical Center, Hackensack, NJ, USA.
J Antimicrob Chemother. 2011 Sep;66(9):2112-8. doi: 10.1093/jac/dkr255. Epub 2011 Jun 22.
The MIC corresponding to daptomycin susceptibility for vancomycin-resistant enterococci (VRE) is ≤ 4 mg/L. Based on the concentration-dependent killing properties of daptomycin, there may be concern about achieving adequate concentrations when the MIC approaches the upper end of the susceptible range (3-4 mg/L). Higher doses of daptomycin may be needed to treat VRE isolates with higher MICs.
We conducted a single-centre retrospective chart review of adult cases with VRE bacteraemia who received daptomycin as initial therapy. The primary outcome was time to microbiological cure (TMC) between standard doses (≤ 6 mg/kg) and high doses (> 6 mg/kg) of daptomycin and whether TMC differed based on MICs. The secondary outcome evaluated the daptomycin MIC distribution and assessed whether recent exposure to vancomycin was associated with higher daptomycin MICs.
Forty-six cases were included in the primary analysis and 60.9% of patients were neutropenic. The two dose groups differed in the baseline characteristics of age, body mass index, blood culture source and catheter removal. Median TMC was 2 days for both dose groups. There was no significant difference in TMC between MIC subgroups of ≤ 2 mg/L versus >2 and ≤ 4 mg/L. For the secondary analysis 227 VRE isolates were evaluated and 62% had daptomycin MICs of 3-4 mg/L. Each daptomycin MIC group had a similar incidence of prior vancomycin exposure.
Based on this retrospective review we did not observe a difference in TMC based on daptomycin dose and MIC; however, there were various limitations to this study, and the study was not powered to detect a difference in TMC. Also, prior vancomycin exposure did not appear to influence daptomycin MICs. The frequency of daptomycin MICs of 3-4 mg/L reported in this study is higher than those reported in the literature.
达托霉素对耐万古霉素肠球菌（VRE）的药敏 MIC 相应地应≤4mg/L。基于达托霉素的浓度依赖性杀菌特性，当 MIC 接近敏感范围（3-4mg/L）的上限时，可能会担心无法达到足够的浓度。对于 MIC 较高的 VRE 分离株，可能需要更高剂量的达托霉素。
我们对接受达托霉素作为初始治疗的 VRE 菌血症成人病例进行了单中心回顾性图表审查。主要结局是标准剂量（≤6mg/kg）和高剂量（>6mg/kg）达托霉素之间的微生物学治愈时间（TMC），以及 TMC 是否因 MIC 而异。次要结局评估了达托霉素 MIC 分布，并评估了近期万古霉素暴露是否与更高的达托霉素 MIC 相关。
在主要分析中纳入了 46 例病例，60.9%的患者中性粒细胞减少。两组在年龄、体重指数、血培养源和导管去除方面的基线特征不同。两组的中位 TMC 均为 2 天。MIC≤2mg/L 与>2mg/L 和≤4mg/L 亚组之间的 TMC 无显著差异。对于二次分析，评估了 227 株 VRE 分离株，其中 62%的达托霉素 MIC 为 3-4mg/L。每个达托霉素 MIC 组的万古霉素暴露史相似。
基于这项回顾性研究，我们没有观察到 TMC 基于达托霉素剂量和 MIC 的差异；然而，这项研究存在各种局限性，并且研究没有能力检测 TMC 的差异。此外，万古霉素暴露似乎不会影响达托霉素 MIC。本研究报告的达托霉素 MIC 为 3-4mg/L 的频率高于文献报道的频率。
