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Penicillin therapy of experimental endocarditis induced by tolerant Streptococcus sanguis and nontolerant
Abstract:
The response of tolerant Streptococcus sanguis and nontolerant Streptococcus mitis infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 mug/ml, respectively, for S. mitis and 0.05 and 6.2 mug/ml, respectively, for S. sanguis. Time-kill studies done in vitro with penicillin concentrations of 2 and 20 mug/ml demonstrated minimal killing of the tolerant strain, with a 3 log difference in survival between the two strains after 24 and 48 h. Both strains produced endocarditis with comparable bacterial densities on the valvular vegetations. Rabbits were treated with procaine penicillin G in two dosage regimens, 80,000 or 5,000 U/kg given every 8 h. There was no difference between bacterial densities in valvular vegetations removed from rabbits infected with either strain after 2, 4, or 6 days of treatment with the high-dose regimen (serum penicillin concentration at 0.5 h, 9.4 mug/ml), despite the fact that serum bactericidal activity against the tolerant strain at 0.5 h was minimal. With the low-dose penicillin regimen (serum concentration at 0.5 h, 2.5 mug/ml), therapy was significantly less effective in the tolerant group only after 6 days of treatment. Similar results were obtained when penicillin was administered in low and high doses to prevent infection. In this animal model of infection, penicillin tolerance was associated with a diminished response to penicillin therapy only when the dose was severely restricted. In the high-dose regimen, there was no difference in the response to penicillin therapy between animals infected with either strain, despite the presence of only minimal serum bactericidal activity in the rabbits infected with the tolerant strain.
Insights
Penicillin therapy effectively treated Streptococcus endocarditis in rabbits, even with tolerant strains, unless doses were severely restricted. High-dose penicillin showed efficacy regardless of bacterial strain tolerance.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Penicillin tolerance in bacteria is a challenge in treating infections.
- Streptococcus species, including Streptococcus sanguis and Streptococcus mitis, are common causes of endocarditis.
Purpose of the Study:
- To compare the efficacy of penicillin therapy against tolerant Streptococcus sanguis and non-tolerant Streptococcus mitis endocarditis in a rabbit model.
- To investigate the impact of penicillin dosage on treatment outcomes in the presence of bacterial tolerance.
Main Methods:
- Established rabbit models of endocarditis using S. sanguis and S. mitis.
- Administered procaine penicillin G in high (80,000 U/kg) and low (5,000 U/kg) dose regimens.
- Monitored bacterial densities in valvular vegetations and serum penicillin concentrations.
Main Results:
- Penicillin tolerance in S. sanguis was characterized by higher minimal bactericidal concentrations and reduced in vitro killing by penicillin.
- High-dose penicillin therapy eradicated both S. sanguis and S. mitis effectively, irrespective of tolerance.
- Low-dose penicillin was less effective against the tolerant S. sanguis strain after prolonged treatment.
Conclusions:
- Penicillin tolerance in Streptococcus endocarditis is associated with a reduced treatment response primarily under severely restricted dosing conditions.
- High-dose penicillin regimens are effective in treating endocarditis caused by both penicillin-tolerant and non-tolerant Streptococcus strains.
- Dosage is a critical factor in overcoming penicillin tolerance in bacterial endocarditis.