Efficacy of teicoplanin in two dosage regimens for experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.
Optimal therapy for the treatment of infections caused by strains of enterococci demonstrating high-level resistance to gentamicin and other aminoglycosides has not been established. The present study examined the efficacy of teicoplanin, a glycopeptide antibiotic active against gram-positive bacterial infections in various animal models, in the treatment of experimental endocarditis due to a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin. Vancomycin was used as a comparative antibiotic. In the first set of experiments, both antimicrobial agents were administered by continuous intravenous infusion for 5 days at dosages which yielded comparable mean levels in serum (plus or minus the standard deviation) of 14.6 +/- 4.3 micrograms/ml for teicoplanin and 14.3 +/- 2.2 micrograms/ml for vancomycin. These regimens proved similarly effective in sterilizing cardiac vegetations (38 versus 50% of treated animals, respectively; P greater than 0.05). Mean (plus or minus the standard deviation) residual bacterial titers within vegetations were reduced to 3.2 +/- 1.2 log10 CFU/g and 3.4 +/- 1.7 log10 CFU/g, respectively. In separate experiments, the potential of teicoplanin to cure endocarditis was assessed, using two dosage regimens: (i) 30 mg/kg per day (mean level in serum, 13 micrograms/ml) for 10 days or (ii) 150 mg/kg per day (mean level in serum, 84 micrograms/ml) for 5 days. Surviving animals were sacrificed 10 days after the discontinuation of therapy. Both teicoplanin regimens were more effective than the comparative vancomycin (150 mg/kg per day) regimen: 92 versus 43% cured (P =0.025) in the standard-dose group, and 82 versus 37% cured (P = 0.015) in the high-dose group. Results in this rat model of enterococcal endocarditis show that teicoplanin may prove useful in the treatment of serious infections due to high level-gentamicin-resistant enterococci in humans.
Yao
J D
JD
Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts.
Thauvin-Eliopoulos
C
C
Eliopoulos
G M
GM
Moellering
R C
RC
D000818:Animals; D004352:Drug Resistance, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000187:drug effects / Q000201:enzymology*; D005839:Gentamicins / Q000494:pharmacology; D006020:Glycopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017334:Teicoplanin; D014640:Vancomycin / Q000627:therapeutic use; D001618:beta-Lactamases / Q000378:metabolism*
D005839:Gentamicins; D006020:Glycopeptides; D017334:Teicoplanin; D014640:Vancomycin; D001618:beta-Lactamases