Daptomycin in Combination With Other Antibiotics for the Treatment of Complicated Methicillin-Resistant Staphylococcus aureus Bacteremia

Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important nosocomial pathogens. Resistance to antibiotic therapy has been known to emerge especially in clinically complex scenarios, resulting in challenges in determining optimal treatment of serious MRSA. Daptomycin, in combination with other antibiotics, has been successfully used in the treatment of these infections, with the aims of resulting in reducing the prevention of antimicrobial resistance and increased killing compared with daptomycin monotherapy. Methods: This article reviews all the published studies that used daptomycin combination therapy for the treatment of bacteremia and associated complicated infections caused by gram-positive organisms, including MRSA. We discuss the rationale of combination antibiotics and the mechanisms that enhance the activity of daptomycin, with special focus on the role of beta-lactam antibiotics. Findings: There are limited clinical data on the use of daptomycin in combination with other antibiotics. Most of this use was as successful salvage therapy in the setting of failing primary, secondary, or tertiary therapy and/or relapsing infection. Synergy between beta-lactams and daptomycin is associated with several characteristics, including increased daptomycin binding and beta-lactam mediated potentiation of innate immunity, but the precise molecular mechanism is unknown. (C) 2014 Elsevier HS Journals, Inc. All rights reserved.