title: Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.
abstract: Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Zasowski
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Trang D
authors.initials: TD
authors.lastname: Trinh
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.|Department of Pharmacy Practice, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Claeys
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.|Department of Pharmacy Practice, Husson University School of Pharmacy, Bangor, Maine, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Casapao
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Noor
authors.initials: N
authors.lastname: Sabagha
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Abdalhamid M
authors.initials: AM
authors.lastname: Lagnf
authors.affiliation: University of Florida, College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Klinker
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.|Department of Pharmacy Services, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Davis
authors.affiliation: Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA M.Rybak@wayne.edu.|Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, USA.|Department of Pharmacy Services, Detroit Medical Center, Detroit, Michigan, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000368:Aged; D016470:Bacteremia / Q000188:drug therapy*; D002511:Cephalosporins / Q000627:therapeutic use*; D017576:Daptomycin / Q000627:therapeutic use; D004696:Endocarditis / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D014640:Vancomycin / Q000627:therapeutic use; D000097583:Ceftaroline
chemical_list: D002511:Cephalosporins; D017576:Daptomycin; D014640:Vancomycin; D000097583:Ceftaroline
keywords: MRSA; bacteremia; beta-lactam; bone and joint infection; daptomycin; infective endocarditis; pneumonia; treatment failure; vancomycin