Tseng Tai-Chung, Chuang Yu-Chung, Yang Jia-Ling, Lin Chi-Ying, Huang Sung-Hsi, Wang Jann-Tay, Chen Yee-Chun, Chang Shan-Chwen
Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan.
Infect Dis Ther. 2023 Feb;12(2):589-606. doi: 10.1007/s40121-022-00754-1. Epub 2023 Jan 11.
High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable.
An observational study of VRE-BSI was performed between 2010-2021 on patients receiving daptomycin monotherapy (≥ 8 mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant β-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses.
Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8 mg/kg and 12 g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P < 0.001), respectively. Multivariable logistic regression analysis predicted lower mortality with fosfomycin combination treatment (adjusted odds ratio, 0.35; 95% confidence interval (CI), 0.17-0.73; P = 0.005). AIPW demonstrated a 17.8% reduced mortality with fosfomycin combinations (95% CI, - 30.6- - 4.9%; P = 0.007). The survival benefit was significant, especially among patients with a lower Pitt bacteremia score or fosfomycin minimum inhibitory concentration (MIC) ≤ 64 mg/l. Fosfomycin combination resulted in higher hypernatremia (10.4% vs. 2.8%, P = 0.04) and hypokalemia (33.3% vs. 15.3%, P = 0.009) compared to daptomycin monotherapy.
The combination of high-dose daptomycin with fosfomycin improved the survival rate of patients with VRE-BSI compared to daptomycin alone. The benefit of the combination was most pronounced for VRE with fosfomycin MIC ≤ 64 mg/l and for patients with a low Pitt bacteremia score.
基于高剂量达托霉素的联合治疗方案被推荐用于耐万古霉素肠球菌（VRE）血流感染（BSI）。临床前数据显示达托霉素/磷霉素联合治疗对VRE有协同作用。然而，尚无比较达托霉素单药治疗与达托霉素/磷霉素联合治疗的临床研究。
2010年至2021年期间，对接受达托霉素单药治疗（≥8mg/kg）或达托霉素联合静脉注射磷霉素的VRE-BSI患者进行了一项观察性研究。排除接受β-内酰胺类联合治疗的患者。主要结局是院内死亡率。采用多变量逻辑回归和增强逆概率加权（AIPW）分析对结局进行分析。
224例患者中，176例接受达托霉素单药治疗，48例接受磷霉素联合治疗。达托霉素和磷霉素的中位剂量分别为9.8mg/kg和12g/天。达托霉素单药治疗组和磷霉素联合治疗组的院内死亡率分别为77.3%和47.9%（P<0.001）。多变量逻辑回归分析预测磷霉素联合治疗的死亡率较低（调整后的优势比为0.35；95%置信区间（CI）为0.17-0.73；P=0.005）。AIPW显示磷霉素联合治疗的死亡率降低了17.8%（95%CI为-30.6--4.9%；P=0.007）。生存获益显著，尤其是在 Pitt 菌血症评分较低或磷霉素最低抑菌浓度（MIC）≤64mg/l 的患者中。与达托霉素单药治疗相比，磷霉素联合治疗导致高钠血症（10.4%对2.8%，P=0.04）和低钾血症（33.3%对15.3%，P=0.009）的发生率更高。
与单独使用达托霉素相比，高剂量达托霉素与磷霉素联合治疗可提高VRE-BSI患者的生存率。对于磷霉素MIC≤64mg/l的VRE患者和Pitt菌血症评分较低的患者，联合治疗的获益最为明显。
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