title: Triple combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a highly penicillin-and glycopeptide-resistant isolate of Enterococcus faecium.
abstract: A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.
authors.affiliation: Groupe de Recherche en Infections Expérimentales, Hôpital Charles Nicolle, Rouen, France.
authors.forename: F
authors.initials: F
authors.lastname: Caron
authors.forename: J F
authors.initials: JF
authors.lastname: Lemeland
authors.forename: G
authors.initials: G
authors.lastname: Humbert
authors.forename: I
authors.initials: I
authors.lastname: Klare
authors.forename: L
authors.initials: L
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004696:Endocarditis / Q000188:drug therapy*; D016984:Enterococcus faecium; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000008:administration & dosage; D011817:Rabbits; D014640:Vancomycin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D014640:Vancomycin