The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study

Tai-Chung Tseng; Yu-Chung Chuang; Jia-Ling Yang; Chi-Ying Lin; Sung-Hsi Huang; Jann-Tay Wang; Yee-Chun Chen; Shan-Chwen Chang

doi:10.1007/s40121-022-00754-1

The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study

Infect Dis Ther. 2023 Feb;12(2):589-606. doi: 10.1007/s40121-022-00754-1. Epub 2023 Jan 11.

Authors

Tai-Chung Tseng¹, Yu-Chung Chuang², Jia-Ling Yang³, Chi-Ying Lin⁴, Sung-Hsi Huang⁵, Jann-Tay Wang³, Yee-Chun Chen³, Shan-Chwen Chang³

Affiliations

¹ Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan.
² Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan. weischuang@gmail.com.
³ Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan.
⁴ Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
⁵ Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Combination; Daptomycin; Fosfomycin; Mortality; Vancomycin-resistant enterococci.

Abstract

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