Journal
CLINICAL THERAPEUTICS
Volume 36, Issue 10, Pages 1317-1333Publisher
ELSEVIER
DOI: 10.1016/j.clinthera.2014.05.061
Keywords
ceftaroline; daptomycin; MRSA; MRSE bacteremia; MSSA; VISA
Categories
Funding
- National Institute of Health, Division of National Institute of Child Health and Human Development (Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy) [U54 HD071600-01]
- Forest Pharmaceuticals (New York, NY)
Ask authors/readers for more resources
Purpose: Guidelines recommend daptomycin combination therapy as an option for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin failure. Recent data suggest that combining daptomycin with a beta-lactam may have unique benefits; however, there are very limited clinical data regarding the use of ceftaroline with daptomycin. Methods: All 26 cases from the 10 medical centers in which ceftaroline plus daptomycin was used for treatment of documented refractory staphylococcal bacteremia from March 2011 to November 2012 were included. In vitro (synergy studies, binding assays, cathelicidin LL-37 killing assays), and in vivo (virulence assays using a murine subcutaneous infection model) studies examining the effects of ceftaroline with daptomycin were also performed. Findings: Daptomycin plus ceftaroline was used in 26 cases of staphylococcal bacteremia (20 MRSA, 2 vancomycin-intermediate S aureus, 2 methicillin-susceptible S aureus [MSSA], 2 methicillin-resistant S epidermidis). Bacteremia persisted for a median of 10 days (range, 3-23 days) on previous antimicrobial therapy. After daptomycin plus ceftaroline was started, the median time to bacteremia clearance was 2 days (range, 1-6 days). In vitro studies showed ceftaroline synergy against MRSA and enhanced MRSA killing by cathelicidin LL-37 and neutrophils. Ceftaroline also induced daptomycin binding in MSSA and MRSA to a comparable degree as nafcillin. MRSA grown in sub-inhibitory concentrations of ceftaroline showed attenuated virulence in a murine subcutaneous infection model. (C) 2014 Elsevier HS Journals, Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available