ROLE OF AMOXICILLIN SERUM LEVELS FOR SUCCESSFUL PROPHYLAXIS OF EXPERIMENTAL ENDOCARDITIS DUE TO TOLERANT STREPTOCOCCI

The importance of amoxicillin serum profiles for successful prophylaxi s of experimental endocarditis in rats was assessed. Animals with cath eter-induced vegetations were challenged intravenously with large inoc ula of Streptococcus sanguis and received one of the following amoxici llin 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 experimenta l endocarditis; in contrast, a second injection 6 h after the first re sulted in successful prophylaxis. Likewise, the three regimens of cont inuous, relatively low-dose regimens prevented infections. Thus, the m ost 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.