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.