Comparing the Outcomes of Ceftaroline plus Vancomycin or Daptomycin Combination Therapy versus Vancomycin or Daptomycin Monotherapy in Adults with Methicillin-Resistant Staphylococcus aureus Bacteremia—A Meta-Analysis

Abstract

Introduction: Combination therapy with daptomycin plus ceftaroline to treat methicillin-resistant Staphylococcus aureus bacteremia has been reported to reduce methicillin-resistant Staphylococcus aureus bacteremia-related mortality. The purpose of the current meta-analysis was to compare the clinical outcome of methicillin-resistant Staphylococcus aureus bacteremia in patients treated with daptomycin or vancomycin plus ceftaroline combination therapy versus daptomycin or vancomycin monotherapy. Methods: Studies were included if they directly compared the efficacy of daptomycin or vancomycin plus ceftaroline combination therapy with that of daptomycin or vancomycin monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteremia in adult patients. Results: One randomized controlled trial and five retrospective studies were included in the meta-analysis. The combination therapy group had an in-hospital mortality, duration of bacteremia, and adverse event rate similar to those patients who had monotherapy. There was less bacteremia recurrence in the combination group. Initial combination therapy with ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia showed a trend of reducing the risk of in-hospital mortality in the current meta-analysis. Conclusions: Randomized controlled trials are needed to further study the role of initial combination therapy with daptomycin or vancomycin plus ceftaroline in the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis

“…While blood culture clearance was demonstrated with combination therapy, the smaller sample size and lack of comparison group prohibited the performance of statistical analyses. A meta-analysis of six trials evaluating either DAP or vancomycin monotherapy vs. combination therapy with CPT showed a statistically significant decrease in bacteremia recurrence with CPT combination therapy compared with monotherapy (OR = 2.95, 95% CI = 1.22–7.15, p = 0.02) but no difference in in-hospital mortality or adverse events [ 75 ]. Because CPT/DAP is resource intensive (cost and administration effort), it is of interest to use the combination for the shortest duration possible.…”

Antibiotic Resistance to Molecules Commonly Prescribed for the Treatment of Antibiotic-Resistant Gram-Positive Pathogens: What Is Relevant for the Clinician?

“…However, it is possible to assert that the use of daptomycin in combination can be considered as standard of care in the context of IE (regardless of the species involved) [21] and in the treatment of viridans streptococci, since in these cases the risk of the emergence of resistance is sufficiently concrete. In other circumstances, combination therapy should be taken into consideration in case of difficult-to-treat infections [15,21,[50][51][52]57].…”

“…As already underlined, ceftaroline has been studied in combination with other anti-MRSA antibiotics (particularly daptomycin) for the treatment of BSI, including IE. This association has been proposed in order to increase the anti-bacterial efficacy and protect daptomycin from the emergence of resistance during treatment [15,21,51,52,57].…”

Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Host, Pathogen, and Treatment

“…It is FDA approved for the treatment of community-acquired pneumonia and acute bacterial skin and skin structure infections (including those with concurrent bacteremia) but is frequently used off-label, either alone or in combination with another antibiotic, as a treatment for MRSAB. The combination of daptomycin and ceftaroline, especially when initiated early in the disease course, is possibly associated with reduced in-hospital mortality compared to monotherapy with vancomycin or daptomycin [ 140 , 141 , 142 ]. Although we are lacking high-quality data to support such an approach, ceftaroline is commonly used in clinical practice in combination with vancomycin or daptomycin to treat persistent MRSAB [ 143 , 144 ].…”