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Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats
J Gavaldà1, J A Capdevila, B Almirante
1Infectious Diseases Research Laboratory, Universitat Autònoma de Barcelona, Spain. gavalda@ar.vhebron.es
Abstract:
A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.
Insights
A rat model of penicillin-resistant Streptococcus pneumoniae pneumonia was developed. Higher doses and prolonged treatment of penicillin, cefotaxime, and cefpirome showed greater efficacy in reducing lung bacterial counts.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Streptococcus pneumoniae is a leading cause of bacterial pneumonia.
- Penicillin resistance in S. pneumoniae poses a significant therapeutic challenge.
- Developing reliable animal models is crucial for evaluating antimicrobial efficacy.
Purpose of the Study:
- To develop a reproducible rat model of pneumonia caused by penicillin-resistant Streptococcus pneumoniae.
- To evaluate the in vivo efficacy of different doses and treatment durations of penicillin, cefotaxime, cefpirome, and vancomycin against this resistant strain.
Main Methods:
- Immunocompetent Wistar rats were intratracheally inoculated with penicillin-resistant S. pneumoniae.
- A fatal pneumonia model was established with high mortality and persistent lung bacterial counts.
- Animals were treated with various doses of penicillin, cefotaxime, cefpirome, and vancomycin or left untreated.
- Therapeutic efficacy was assessed based on bacterial titers in lung tissue under different treatment protocols (short-term vs. prolonged).
Main Results:
- All tested antimicrobial agents initially showed similar efficacies.
- Prolonged treatment with higher doses of penicillin, cefotaxime, and cefpirome led to a greater reduction in lung bacterial titers compared to lower penicillin doses.
- Extended vancomycin treatment was more effective than low-dose penicillin but less effective than high-dose penicillin or cefpirome.
Conclusions:
- The developed rat model is a simple and effective tool for studying pneumonia caused by penicillin-resistant S. pneumoniae in immunocompetent hosts.
- Higher doses and longer treatment durations of beta-lactam antibiotics (penicillin, cefotaxime, cefpirome) are more effective against penicillin-resistant S. pneumoniae pneumonia.
- This model can be utilized to explore disease pathophysiology and optimize therapeutic strategies for resistant bacterial pneumonia.