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Role of amoxicillin serum levels for successful prophylaxis of experimental endocarditis due to tolerant streptococci.

Authors
Journal
The Journal of Infectious Diseases
0022-1899
Publisher
Oxford University Press
Publication Date
Volume
169
Issue
6
Identifiers
DOI: 10.1093/infdis/169.6.1397
Keywords
  • Amoxicillin/Administration & Dosage
  • Amoxicillin/Blood
  • Animals
  • Dose-Response Relationship
  • Drug
  • Drug Resistance
  • Microbial
  • Endocarditis/Microbiology
  • Endocarditis/Prevention & Control
  • Female
  • Rats
  • Rats
  • Wistar
  • Streptococcal Infections/Microbiology
  • Streptococcal Infections/Prevention & Control
  • Streptococcus Sanguis/Drug Effects

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.

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