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Treatment of experimental endocarditis due to penicillin-resistant Streptococcus pneumoniae
M L Fernández Guerrero1, F Arbol, C Verdejo
1Division of Infectious Diseases, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain.
Abstract:
Using two strains of pneumococci for which MICs of penicillin were 1 and 4 micrograms/ml, those of cefotaxime were 0.01 and 0.5 micrograms/ml, and those of teicoplanin were 0.01 and 0.1 micrograms/ml, we studied the efficacy of different dosages of penicillin, cefotaxime, and teicoplanin in the treatment of experimental pneumococcal endocarditis in rabbits. Animals treated with dosages of penicillin G procaine needed to achieve levels in serum near the MIC for pneumococci showed a significant reduction in log10 CFU per gram of vegetation, as compared with the control (P < 0.001), although only 20% of the animals showed sterile vegetations. When levels of penicillin in serum were in the range of three- to fourfold the MIC, a greater reduction in log10 CFU per gram of vegetation was seen, and 88% of the animals showed sterile vegetations. Only the regimen of penicillin that provided concentrations in serum above the MIC throughout the interval between two doses provided constant sterilization of the cardiac vegetations. Dosages of cefotaxime and teicoplanin selected to achieve concentrations in serum equivalent to that obtained in humans during treatment resulted in levels of antimicrobial agents in serum hundreds or thousands of times higher than the MICs for the infecting strains. In terms of antimicrobial efficacy, cefotaxime and teicoplanin were equivalent to regimens with high dosages of penicillin.
Insights
Penicillin, cefotaxime, and teicoplanin efficacy in treating experimental pneumococcal endocarditis in rabbits was evaluated. High-dose penicillin or cefotaxime and teicoplanin achieved significant bacterial reduction, with sustained high penicillin levels ensuring vegetation sterilization.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pneumococcal endocarditis is a serious infection requiring effective antimicrobial therapy.
- Understanding the comparative efficacy of different antibiotics is crucial for treatment optimization.
Purpose of the Study:
- To evaluate the efficacy of various dosages of penicillin, cefotaxime, and teicoplanin in a rabbit model of experimental pneumococcal endocarditis.
- To determine the relationship between antimicrobial serum levels and treatment outcomes.
Main Methods:
- Two strains of *Streptococcus pneumoniae* with defined penicillin, cefotaxime, and teicoplanin minimum inhibitory concentrations (MICs) were used.
- Rabbits with experimentally induced endocarditis were treated with different dosages of the antibiotics.
- Bacterial burden (log10 CFU per gram of vegetation) and vegetation sterility were assessed.
Main Results:
- Penicillin G procaine treatment led to significant bacterial reduction compared to controls, with higher efficacy at three- to fourfold the MIC.
- Sustained penicillin serum concentrations above the MIC throughout dosing intervals resulted in consistent vegetation sterilization.
- Cefotaxime and teicoplanin, at human-equivalent doses, achieved serum levels far exceeding MICs and demonstrated efficacy comparable to high-dose penicillin regimens.
Conclusions:
- Achieving and maintaining antimicrobial serum concentrations significantly above the MIC is critical for effective treatment of pneumococcal endocarditis.
- Both cefotaxime and teicoplanin show comparable efficacy to high-dose penicillin in this experimental model.
- Optimized dosing strategies are essential for successful eradication of *Streptococcus pneumoniae* in endocarditis.