Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Economics, National Chengchi University, Taipei, Taiwan.
Clin Microbiol Infect. 2016 Oct;22(10):890.e1-890.e7. doi: 10.1016/j.cmi.2016.07.018. Epub 2016 Jul 27.
Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21-0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6-9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17-0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09-0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45-4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia.
治疗万古霉素耐药肠球菌（VRE）血流感染的选择有限。比较达托霉素或利奈唑胺治疗 VRE 血流感染的研究结果相互矛盾，并提示达托霉素剂量不足。不同达托霉素剂量的反应尚未得到研究。我们进行了一项多中心前瞻性队列研究，比较利奈唑胺和达托霉素（≥6mg/kg）治疗 VRE 血流感染。主要结局为 14 天死亡率。我们使用多变量逻辑回归分析进行结果分析，并使用广义加性模型进行剂量依赖性反应估计。共纳入 212 例患者（达托霉素组 141 例，利奈唑胺组 71 例）。达托霉素组全因 14 天死亡率较高（36.9%比 21.1%；p=0.03）。在逻辑回归中调整混杂因素后，利奈唑胺组死亡率较低（调整后的优势比（aOR），0.45；95%置信区间（CI），0.21-0.96；p=0.04）。广义加性模型显示，较高剂量的达托霉素（≥9mg/kg）与较低剂量的达托霉素（6-9mg/kg）相比，生存率更高。逻辑回归显示，利奈唑胺（aOR，0.36；95%CI，0.17-0.79；p=0.01）和较高剂量的达托霉素（aOR，0.26；95%CI，0.09-0.74；p=0.01）与较低剂量的达托霉素相比，独立预测死亡率较低。利奈唑胺在死亡率方面并不优于高剂量的达托霉素（aOR，1.40；95%CI，0.45-4.37；p=0.57）。高剂量的达托霉素死亡率低于低剂量的达托霉素。尽管低剂量达托霉素的死亡率高于利奈唑胺，但与高剂量达托霉素相比，利奈唑胺并未带来生存获益。我们的研究结果表明，目前推荐的达托霉素剂量对于治疗 VRE 菌血症并不理想。
