比较标准剂量、中剂量和高剂量达托霉素治疗退伍军人事务部患者耐万古霉素肠球菌菌血症的疗效和安全性。
Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients.
机构信息
Department of Pharmacy, Barnes-Jewish Hospital, St Louis, Missouri, USA.
Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
出版信息
Clin Infect Dis. 2017 Mar 1;64(5):605-613. doi: 10.1093/cid/ciw815.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.
背景
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。
方法
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。
结果
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）。
结论
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。
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