Department of Pharmacy, Barnes-Jewish Hospital, St Louis, Missouri, USA.
Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
Clin Infect Dis. 2017 Mar 1;64(5):605-613. doi: 10.1093/cid/ciw815.
Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are associated with significant mortality. Daptomycin exhibits concentration-dependent activity vs VRE in vitro, yet the clinical impact of higher-dose strategies remains unclear.
We performed a national retrospective cohort study of hospitalized Veterans Affairs patients treated with standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin for VRE-BSI. Patient-related, microbiological, and outcomes data were abstracted from clinical databases. The primary outcome was overall survival, evaluated by Cox regression. Secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation.
A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose (hazard ratio [HR], 2.68; 95% confidence interval; [CI], 1.33-3.06; P = .002) and medium-dose (HR, 2.66; 95% CI, 1.33-3.92; P = .003) daptomycin were associated with poorer survival. After adjusting for confounders, the relationship between poorer survival and standard-dose (adjusted HR [aHR], 2.58; 95% CI, 1.27-4.88; P = .004) and medium-dose (aHR, 2.52; 95% CI, 1.27-5.00; P = .008) daptomycin persisted. Thirty-day mortality was significantly lower among high-dose daptomycin-treated patients compared with other dosing strategies (risk ratio, 0.83; 95% CI, .74-.94; P = .015). Compared with standard-dose daptomycin, both medium-dose (HR, 0.78; 95% CI, .55-.90; P = .012) and high-dose daptomycin (HR, 0.70; 95% CI, .41-.84; P = .006) were associated with significantly improved microbiological clearance. No difference in the risk of CPK elevation was observed between the treatment groups (P = .504).
High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.
耐万古霉素肠球菌血流感染（VRE-BSI）与显著的死亡率相关。达托霉素对 VRE 具有浓度依赖性的体外活性，但高剂量策略的临床影响尚不清楚。
我们对接受标准剂量（总体重 6 毫克/公斤）、中剂量（总体重 8 毫克/公斤）或高剂量（≥10 毫克/公斤）达托霉素治疗 VRE-BSI 的退伍军人事务部住院患者进行了全国性回顾性队列研究。从临床数据库中提取患者相关、微生物学和结局数据。主要结局是通过 Cox 回归评估的总生存。次要结局包括 30 天死亡率、微生物学清除时间和肌酸磷酸激酶（CPK）升高。
共纳入 911 例患者（标准剂量组 n=709；中剂量组 n=142；高剂量组 n=60）。与高剂量达托霉素相比，标准剂量（危险比[HR]，2.68；95%置信区间[CI]，1.33-3.06；P=0.002）和中剂量（HR，2.66；95% CI，1.33-3.92；P=0.003）达托霉素与较差的生存相关。在调整混杂因素后，标准剂量（调整 HR[aHR]，2.58；95% CI，1.27-4.88；P=0.004）和中剂量（aHR，2.52；95% CI，1.27-5.00；P=0.008）与较差的生存之间的关系仍然存在。与其他剂量策略相比，高剂量达托霉素治疗患者的 30 天死亡率显著降低（风险比，0.83；95% CI，0.74-0.94；P=0.015）。与标准剂量达托霉素相比，中剂量（HR，0.78；95% CI，0.55-0.90；P=0.012）和高剂量（HR，0.70；95% CI，0.41-0.84；P=0.006）达托霉素均与微生物学清除率显著提高相关。治疗组之间 CPK 升高的风险无差异（P=0.504）。
高剂量达托霉素与 VRE-BSI 患者的生存和微生物学清除率改善相关。
