Affiliation:
1. Department of Pharmacy Services, Detroit Receiving Hospital/University Health Center, Michigan.
Abstract
The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of vancomycin. Eight concentrations of each drug ranging from 15 to 150 micrograms/ml were studied in two series which correspond to the concentrations in serum achieved with low- (6 mg/kg of body weight once daily) and high-dose (30 mg/kg once daily) teicoplanin. Overall, the bactericidal rate of teicoplanin was lower than that of vancomycin. In the presence of serum, the bactericidal rate of teicoplanin in PHS-SMHB was lower than that in SMHB, often resulting in only one log10 drop in CFU over a 24-h period. There was no statistical difference in the bactericidal rates of high- and low-concentration teicoplanin in either medium. Additionally, concentration-dependent killing in SMHB was not evident with either agent. The bactericidal rates of teicoplanin and vancomycin in a 1:1 mixture of serum ultrafiltrate and SMHB at 60 micrograms/ml were also studied. It was noted that the bactericidal rate of neither agent was affected by the presence of serum ultrafiltrate. This finding is consistent with teicoplanin's high degree of protein binding (reported to be greater than 90% in undiluted serum) and further substantiates the hypothesis that only the free drug is active against microorganisms. These data support protein binding as being a factor in teicoplanin activity against S. aureus.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference26 articles.
1. Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections;Bibler M. R.;Antimicrob. Agents Chemother.,1987
2. Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections;Calain P.;J. Infect. Dis.,1987
3. Effects of dosage, peak and trough concentrations in serum, protein binding, and bactericidal rate on efficacy of teicoplanin in a rabbit model of endocarditis;Chambers H. F.;Antimicrob. Agents Chemother.,1990
4. Evaluation of antibiotic diffusion into cardiac vegetations by quantitative autoradiography;Cremieux A. C.;J. Infect. Dis.,1989
5. Role of pharmacokinetics in the outcome of infections;Drusano G. L.;Antimicrob. Agents Chemother.,1988
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