title: A combination of ceftaroline and daptomycin has synergistic and bactericidal activity in vitro against daptomycin nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA).
abstract: There is an urgent need to optimize therapeutic options in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who have failed conventional therapy. Two clinical isolates were obtained from a 68-year-old male with persistent MRSA bacteremia before and after the development of daptomycin nonsusceptibility. The pharmacodynamic activity of monotherapies and combinations of ceftaroline, daptomycin, cefoxitin, nafcillin and vancomycin were evaluated in time-kill experiments versus 108CFU/mL of the pre- and post-daptomycin nonsusceptible MRSA isolates. Cefoxitin, nafcillin and vancomycin alone or in combination with ceftaroline failed to generate prolonged bactericidal activity against the post-daptomycin nonsusceptible isolate whereas a ceftaroline-daptomycin combination resulted in 6, 24 and 48 h log10(CFU/mL) reductions of 3.90, 4.40 and 6.32. Population analysis profiles revealed a daptomycin heteroresistant subpopulation of the pre-daptomycin nonsusceptible MRSA isolate that expanded by >10,000× on daptomycin agar containing 2-16 mg/L in the post-daptomycin nonsusceptible isolate. Daptomycin and ceftaroline combinations may be promising against persistent MRSA bacteremia.
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Iffat
authors.initials: I
authors.lastname: Shafiq
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Zackery P
authors.initials: ZP
authors.lastname: Bulman
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Spitznogle
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Osorio
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Irene S
authors.initials: IS
authors.lastname: Reilly
authors.affiliation: b Infectious Diseases Department, Veterans Affairs Western New York Healthcare System , Buffalo , NY , USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Lesse
authors.affiliation: b Infectious Diseases Department, Veterans Affairs Western New York Healthcare System , Buffalo , NY , USA.
authors.forename: Ganapathi I
authors.initials: GI
authors.lastname: Parameswaran
authors.affiliation: b Infectious Diseases Department, Veterans Affairs Western New York Healthcare System , Buffalo , NY , USA.
authors.forename: Kari A
authors.initials: KA
authors.lastname: Mergenhagen
authors.affiliation: a Laboratory for Antimicrobial Pharmacodynamics, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences , Buffalo , NY , USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Tsuji
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D002511:Cephalosporins / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D050296:Microbial Viability / Q000187:drug effects*; D013203:Staphylococcal Infections / Q000382:microbiology; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017576:Daptomycin; D000097583:Ceftaroline
keywords: Daptomycin; MRSA; bacteremia; ceftaroline; daptomycin nonsusceptible