title: Daptomycin compared with teicoplanin and vancomycin for therapy of experimental Staphylococcus aureus endocarditis.
abstract: The efficacies of daptomycin, teicoplanin, and vancomycin were compared in the therapy of experimental Staphylococcus aureus endocarditis. Rabbits infected with either of two methicillin-susceptible strains (SA-12871 or its moderately teicoplanin-resistant derivative SA-12873) or a methicillin-resistant S. aureus strain (MRSA-494) were treated with daptomycin, 8 mg/kg of body weight, every 8 h; teicoplanin, 12.5 mg/kg (low-dose teicoplanin [teicoplanin-LD], excluding MRSA-494) or 40 mg/kg (high-dose teicoplanin [teicoplanin-HD]) every 12 h; or vancomycin, 17.5 mg/kg every 6 h, for 4 days. Compared with no treatment daptomycin, teicoplamin-HD, and vancomycin significantly reduced bacterial counts of all test strains in vegetations and renal and splenic tissues (P less than 0.001). Teicoplanin-LD was equally effective against SA-12871 but failed against SA-12873, with three of six animals still being bacteremic at the end of therapy. For SA-12871, daptomycin was as effective as teicoplanin-HD and was superior to teicoplanin-LD and vancomycin (P = 0.02) in lowering vegetation bacterial counts. There were no differences between daptomycin, teicoplanin-HD, or vancomycin in the reduction of bacterial counts in tissues for any of the test strains. In rabbits infected with SA-12871, vegetations from 33% of teicoplanin-LD-treated, 6% of teicoplanin-HD-treated, and 13% of daptomycin-treated animals yielded organisms for which there were up to eightfold increases in the MICs. Resistance may have contributed to early death in one daptomycin-treated animal. No increases in the MICs for the test strain were detected in animals infected with SA-12873 or MRSA-494. We conclude that in this model and against these strains of S. aureus, daptomycin and teicoplanin-HD are as efficacious as vancomycin, but diminished susceptibility to both can develop during therapy.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: G W
authors.initials: GW
authors.lastname: Kaatz
authors.forename: S M
authors.initials: SM
authors.lastname: Seo
authors.forename: V N
authors.initials: VN
authors.lastname: Reddy
authors.forename: E M
authors.initials: EM
authors.lastname: Bailey
authors.forename: M J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D017576:Daptomycin; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006020:Glycopeptides / Q000097:blood / Q000627:therapeutic use; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000097:blood / Q000627:therapeutic use; D011485:Protein Binding; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy*; D017334:Teicoplanin; D014640:Vancomycin / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D006020:Glycopeptides; D010455:Peptides; D017334:Teicoplanin; D014640:Vancomycin; D017576:Daptomycin