Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Clin Infect Dis. 2017 Apr 15;64(8):1026-1034. doi: 10.1093/cid/cix024.
Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined.
We conducted a prospective, observational, cohort study during 2010-2015. We included patients who received a daptomycin dose of ≥6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis.
We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ≤2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7-9 mg/kg, and 5/25 (20%) for a dose of ≥9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25-49.62; P=.003) and 7-9 mg/kg (aOR, 5.01; 95% CI, 1.14-21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase.
Higher daptomycin doses (≥9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment.
耐万古霉素肠球菌（VRE）血流感染（BSI）的治疗选择有限。达托霉素虽然目前尚未批准用于该适应症，但常被用于治疗 VRE-BSI。但其最佳剂量仍需确定。
我们在 2010 年至 2015 年期间进行了一项前瞻性、观察性、队列研究。我们纳入了接受达托霉素剂量≥6mg/kg 治疗达托霉素敏感 VRE 引起的 VRE-BSI 的患者。主要终点为 14 天死亡率，并进行多变量逻辑回归分析以进行结果分析。
我们纳入了 112 例接受达托霉素治疗 VRE-BSI 且临床结局可评估的患者。78 例（69.6%）分离株的达托霉素最小抑菌浓度（MIC）为 4mg/L，34 例（30.4%）为≤2mg/L。总体死亡率为 40/112（35.7%）。未调整的死亡率为：达托霉素剂量<7mg/kg 组为 18/36（50.0%），剂量为 7-9mg/kg 组为 17/51（33.3%），剂量≥9mg/kg 组为 5/25（20%）（P=0.05）。与剂量<7mg/kg（调整后的优势比[aOR]，10.57；95%置信区间[CI]，2.25-49.62；P=0.003）和 7-9mg/kg（aOR，5.01；95%CI，1.14-21.98；P=0.03）相比，达托霉素剂量≥9mg/kg 组的结果更好。达托霉素 MIC 与死亡率之间无显著差异。达托霉素剂量与肌酸激酶升高之间无关联。
VRE-BSI 患者中，较高的达托霉素剂量（≥9mg/kg）与死亡率降低相关。我们的结果表明，需要考虑更高剂量的达托霉素来治疗 VRE-BSI。
