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Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of
Abstract:
Penicillin prophylaxis against experimental endocarditis due to a strain of Streptococcus intermedius 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 killing.
Insights
Penicillin prophylaxis prevented experimental streptococcal endocarditis in rats, even when its concentration was below the minimum bactericidal level. This suggests penicillin may act through non-bactericidal mechanisms to prevent endocarditis.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Bacterial endocarditis is a serious infection, often caused by Streptococcus species.
- Penicillin is a common prophylactic antibiotic, but its efficacy against certain strains requires further investigation.
- Understanding the mechanism of penicillin prophylaxis is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate the efficacy of penicillin prophylaxis against experimental endocarditis caused by a penicillin-resistant strain of Streptococcus intermedius.
- To determine the mechanism by which penicillin may prevent endocarditis, focusing on bactericidal activity.
Main Methods:
- Rats were used to model experimental endocarditis.
- Minimum bactericidal concentration (MBC) of penicillin for the Streptococcus intermedius strain was determined.
- Penicillin serum levels and bactericidal activity were measured at various time points after administration.
- Timed kill curves were performed to assess penicillin's killing activity over time.
- Endocarditis prevention was evaluated using the ID90 (minimum bacterial inoculum to produce endocarditis in 90% of control animals).
Main Results:
- The MBC of penicillin for the tested Streptococcus intermedius strain was high ( > 64 mg/l).
- Achieved penicillin serum levels in rats and humans were below the MBC.
- Penicillin exhibited limited bactericidal activity in vitro, with no significant reduction in colony-forming units within 6 hours.
- No detectable bactericidal activity was found in serum at the time of bacterial challenge.
- Despite these findings, penicillin successfully prevented endocarditis in the experimental model.
Conclusions:
- Penicillin prophylaxis can prevent experimental streptococcal endocarditis even when serum concentrations are below the MBC.
- The findings suggest that penicillin may prevent endocarditis through mechanisms other than direct bacterial killing.
- Further research is warranted to elucidate the non-bactericidal mechanisms of penicillin in endocarditis prevention.