title: Role of amoxicillin serum levels for successful prophylaxis of experimental endocarditis due to tolerant streptococci.
abstract: The importance of amoxicillin serum profiles for successful prophylaxis of experimental endocarditis in rats was assessed. Animals with catheter-induced vegetations were challenged intravenously with large inocula of Streptococcus sanguis and received one of the following amoxicillin dosages: single or multiple bolus injection of 40 mg/kg; 40 mg/kg administered as a continuous infusion over 12 h; or either 9 or 18 mg/kg administered over 12 or 24 h, respectively. The regimen producing a single transient high peak serum level failed to prevent experimental endocarditis; in contrast, a second injection 6 h after the first resulted in successful prophylaxis. Likewise, the three regimens of continuous, relatively low-dose regimens prevented infections. Thus, the most important parameter for successful prophylaxis was the duration of inhibitory concentration of the drug in the serum. The total dose of antibiotic, the peak serum levels, or the area-under-the-curve values were not predictive of successful prophylaxis.
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Fluckiger
authors.forename: P
authors.initials: P
authors.lastname: Francioli
authors.forename: J
authors.initials: J
authors.lastname: Blaser
authors.forename: M P
authors.initials: MP
authors.lastname: Glauser
authors.forename: P
authors.initials: P
authors.lastname: Moreillon
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004696:Endocarditis / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D013290:Streptococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013298:Streptococcus sanguis / Q000187:drug effects
chemical_list: D000658:Amoxicillin