Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of penicillin

Penicillin prophylaxis against experimental endocarditis due to a strain of Streptococcus intermedtus isolated from a patient with endocarditis was studied in rats. The minimum bactericidal concentration of penicillin for this strain was more than 64 mg/l and was higher than the peak penicillin serum level obtained in rats 30 min after the iv injection of 60 mg/kg, and in man after an oral dose of 2 g of phenoxymethyl penicillin. Moreover timed kill curves performed in the presence of 64 mg/l of penicillin showed no decrease in the number of colony-forming units during the first 6 h of incubation and only a 95% decrease after 24 h. In addition, no bactericidal activity could be detected in the serum 30 min after penicillin injection, that is at the time of bacterial challenge. Using the minimum bacterial inoculum needed to produce endocarditis in 90% of control animals (ID90), penicillin successfully prevented endocarditis due to this strain. We conclude that penicillin may prevent streptococcal endocarditis by other mechanisms than bacterial killin