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.
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.
Caron
F
F
Groupe de Recherche sur les Anti-Microbiens, Hôpital Charles Nicolle, Rouen, France.
Pestel
M
M
Kitzis
M D
MD
Lemeland
J F
JF
Humbert
G
G
Gutmann
L
L
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
D005839:Gentamicins; D010406:Penicillins; D017334:Teicoplanin; D014640:Vancomycin; D002443:Ceftriaxone