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Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of
K Tateda1, K Takashima, H Miyazaki
1Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. kazu@sirius.med.toho-u.ac.jp
Abstract:
The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.
Insights
This study introduces a new mouse model for studying penicillin-resistant Streptococcus pneumoniae pneumonia. Imipenem and vancomycin showed the most promise in treating this infection in mice.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Penicillin-resistant Streptococcus pneumoniae poses a significant public health threat.
- Developing effective treatments requires reliable animal models for studying pneumonia caused by these resistant strains.
Purpose of the Study:
- To establish and validate a CBA/J mouse model for evaluating antibiotic efficacy against penicillin-resistant Streptococcus pneumoniae pneumonia.
- To compare the efficacy of various antibiotics, including imipenem, vancomycin, cefotaxime, and penicillin G, in treating this infection model.
Main Methods:
- CBA/J mice were infected with clinical isolates of Streptococcus pneumoniae, including penicillin-susceptible and resistant strains.
- Antibiotic efficacy was assessed by pulmonary bacterial clearance, survival rates, and pharmacokinetic profiling in infected lungs.
- Doses and administration intervals of antibiotics were systematically evaluated.
Main Results:
- The CBA/J mouse model successfully demonstrated susceptibility to both penicillin-susceptible and penicillin-resistant S. pneumoniae strains.
- Imipenem and vancomycin were the most effective antibiotics against penicillin-resistant S. pneumoniae, showing significant bacterial clearance and improved survival rates.
- Vancomycin exhibited a superior pharmacokinetic profile in infected lungs compared to other tested antibiotics.
Conclusions:
- The CBA/J mouse pneumonia model is a valuable tool for assessing antibiotic efficacy against penicillin-resistant S. pneumoniae.
- Imipenem and vancomycin are identified as potentially superior therapeutic agents for treating penicillin-resistant pneumococcal pneumonia.