Daptomycin versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection with or without Endocarditis: A Systematic Review and Meta-Analysis.

Alberto Enrico Maraolo,Davide Fiore Bavaro,Ivan Gentile,Agnese Giaccone,Annalisa Saracino

doi:10.3390/antibiotics10081014

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of invasive infections, mainly bloodstream infections (BSI) with or without endocarditis. The purpose of this meta-analysis was to compare vancomycin, the mainstay treatment, with daptomycin as therapeutic options in this context. Materials: PubMed, Embase and the Cochrane Database were searched from their inception to 15 February 2020. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, persistence of infection, length-of-stay, antibiotic discontinuation due to adverse events (AEs) and 30-day re-admission. This study was registered with PROSPERO, CRD42020169413. Results: Eight studies (1226 patients, 554 vs. 672 in daptomycin vs. vancomycin, respectively) were included. No significant difference in terms of overall mortality was observed [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.40–1.33, I2 = 67%]. Daptomycin was associated with a significantly reduced risk of clinical failure (OR 0.58, 95% CI 0.38–0.89, I2 = 60%), as confirmed by pooling adjusted effect sizes (adjusted OR against the use of vancomycin 1.94, 95%CI 1.33–1.82, I2 = 41%), and was linked with fewer treatment-limiting AEs (OR 0.15, 95%CI 0.06–0.36, I2 = 19%). No difference emerged between the two treatments as secondary outcomes. Results were not robust to unmeasured confounding (E-value lower than 95% CI 1.00 for all-cause mortality). Conclusions: Against MRSA BSI, with or without endocarditis, daptomycin seems to be associated with a lower risk of clinical failure and treatment-limiting AEs compared with vancomycin. Further studies are needed to better characterize the differences between the two drugs.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis are still associated with a significant disease burden, as well as with a remarkable mortality, ranging from 20% to at least 40% [1,2,3,4], which is generally higher than the death rate linked with methicillin-susceptible S. aureus (MSSA) infections, considering that methicillinresistance is an independent risk factor for mortality [5]
Several strategies to optimize the management of S. aureus bloodstream infections (BSI) with or without endocarditis have been suggested, including the development of a series of bundles [6] in order to standardize the “gold standard” of care
The results of our meta-analysis, the largest and the first that has been completed on this topic to date, suggest that daptomycin use is associated with a reduced clinical failure and is better tolerated than vancomycin for the treatment of patients with MRSA infections without lung involvement

Summary

Introduction

VAN is still considered the “backbone” of MRSA infections, serious concerns have been raised over the years, stemming from factors such as slow bactericidal activity, low therapeutic index, limited tissue penetration, unfavorable safety profile, as well as increasing reports of resistance and failure [10]. In this regard, the principal alternative for the treatment of MRSA BSI and endocarditis is DAP, a lipopeptide featuring significant bactericidal activity and an appreciable tolerability profile [9]. DAP was approved for BSI and right-sided endocarditis by S. aureus following the results of a non-inferiority trial by Fowler and colleagues [11]

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