title: Comparison of different beta-lactam-glycopeptide-gentamicin combinations for an experimental endocarditis caused by a highly beta-lactam-resistant and highly glycopeptide-resistant isolate of Enterococcus faecium.
abstract: A synergistic bactericidal effect between penicillin, vancomycin, and gentamicin has been described against enterococci highly resistant to beta-lactams and glycopeptides. Since such a synergy was also observed in vitro between ceftriaxone, teicoplanin, and gentamicin against Enterococcus faecium 70/90, the efficacy of different combinations including penicillin or ceftriaxone, vancomycin or teicoplanin, and gentamicin was compared in vivo in experimental endocarditis. In vitro, all four triple combinations provided a bactericidal effect. In rabbits, after a 5-day treatment, the ceftriaxone-vancomycin-gentamicin combination was the most effective, both in reducing the total bacterial titers and in eradicating the subpopulation resistant to the synergy. Compared with the 5-day regimen, 10- and 20-day regimens of ceftriaxone-vancomycin-gentamicin, each followed by a 3-day antibiotic-free period, increased the number of sterilized animals but failed to avoid the emergence of resistant bacteria, which occurred in 10%-20% of animals.
authors.affiliation: Groupe de Recherche sur les Anti-Microbiens, Hôpital Charles Nicolle, Rouen, France.
authors.forename: F
authors.initials: F
authors.lastname: Caron
authors.forename: M
authors.initials: M
authors.lastname: Pestel
authors.forename: M D
authors.initials: MD
authors.lastname: Kitzis
authors.forename: J F
authors.initials: JF
authors.lastname: Lemeland
authors.forename: G
authors.initials: G
authors.lastname: Humbert
authors.forename: L
authors.initials: L
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D010406:Penicillins / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D012008:Recurrence; D017334:Teicoplanin / Q000494:pharmacology / Q000627:therapeutic use; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005839:Gentamicins; D010406:Penicillins; D017334:Teicoplanin; D014640:Vancomycin; D002443:Ceftriaxone