title: Daptomycin in combination with other antibiotics for the treatment of complicated methicillin-resistant Staphylococcus aureus bacteremia.
abstract: OBJECTIVE
  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 β-lactam antibiotics.
  
  
  RESULTS
  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 β-lactams and daptomycin is associated with several characteristics, including increased daptomycin binding and β-lactam-mediated potentiation of innate immunity, but the precise molecular mechanism is unknown.
  
  
  CONCLUSIONS
  Use of daptomycin in combination with other antibiotics, especially β-lactams, offers a promising treatment option for complicated MRSA bacteremia in which emergence of resistance during treatment may be anticipated. Because it is currently not possible to differentiate complicated from uncomplicated bacteremia at the time of presentation, combination therapy may be considered as first-line therapy, with de-escalation to monotherapy in uncomplicated cases and cases with stable pharmacologic and surgical source control.
authors.affiliation: Westchester Medical Center, New York Medical College, Valhalla, New York.
authors.forename: Abhay
authors.initials: A
authors.lastname: Dhand
authors.affiliation: University of California, San Diego School of Medicine, La Jolla, California. Electronic address: gsakoulas@ucsd.edu.
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus; D013203:Staphylococcal Infections / Q000188:drug therapy*; D047090:beta-Lactams / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D017576:Daptomycin
keywords: MRSA; Staphylococcus aureus; combination therapy; daptomycin; synergy; β-lactams