title: Treatment of high-level gentamicin-resistant Enterococcus faecalis endocarditis with daptomycin plus ceftaroline.
abstract: A recurrent case of left-sided endocarditis caused by high-level aminoglycoside-resistant Enterococcus faecalis was successfully treated with ceftaroline and daptomycin. This combination demonstrated excellent synergy in vitro. Mechanistically, ceftaroline enhanced binding of daptomycin to the cell membrane and sensitized E. faecalis to killing by human cathelicidin LL-37, a cationic innate host defense peptide. Daptomycin plus ceftaroline may be considered in salvage therapy in E. faecalis endovascular infections and requires further study.
authors.affiliation: Department of Pediatric Pharmacology and Drug Discovery, University of California San Diego School of Medicine, La Jolla, California, USA. gsakoulas@ucsd.edu
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Poochit
authors.initials: P
authors.lastname: Nonejuie
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Joseph
authors.initials: J
authors.lastname: Pogliano
authors.forename: Nancy
authors.initials: N
authors.lastname: Crum-Cianflone
authors.forename: Fadi
authors.initials: F
authors.lastname: Haddad
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D013293:Enterococcus faecalis / Q000187:drug effects / Q000302:isolation & purification; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D054804:Cathelicidins; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002511:Cephalosporins; D017576:Daptomycin; D005839:Gentamicins; D054804:Cathelicidins; D000097583:Ceftaroline