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The mouse peritonitis model: present and future use
1Department of Clinical Microbiology, Statens Seruminstitut, Copenhagen, Denmark.
Abstract:
The mouse peritonitis model was the first experimental animal model to be used in antibiotic research in 1935, where it proved the effect of Prontosil and derivative sulphonamides against Streptococcus pyogenes in vivo. Since then the mouse peritonitis model has been a natural step in testing antibiotics in vivo before moving to larger animals or humans. Only a few bacteria are naturally virulent to mice, e.g. Streptococcus pneumoniae, but the mice can be rendered susceptible to most human pathogens by inhibition of one or more parts of the natural defence of the animals. For measuring the effect of antibiotics two parameters are usually considered: bacterial counts in fluids or tissues, or death/survival of the animal. Both parameters have flaws, but death is usually used, owing to the ease of observation and quantification by calculation of the 50% effective (protective or curative) doses. With these parameters a number of significant factors of importance for antibiotic effect have been detected or proven in this model. Together with the recent insight into the correlation of pharmacokinetic behaviour between these small animals and man, it is predicted that the mouse peritonitis model will continue to be an important means of studying the effect of antibiotics in vivo.
Insights
The mouse peritonitis model, established in 1935, remains crucial for in vivo antibiotic research. This model effectively evaluates antibiotic efficacy against various pathogens, aiding drug development before human trials.
Area of Science:
- Pharmacology and Microbiology
- Infectious Diseases
- Experimental Therapeutics
Background:
- The mouse peritonitis model was the first experimental animal model used in antibiotic research in 1935.
- It has since been a standard in vivo model for testing antibiotics before progression to larger animals or humans.
- While few bacteria are naturally virulent to mice, host defenses can be modulated to increase susceptibility to human pathogens.
Purpose of the Study:
- To review the historical significance and continued utility of the mouse peritonitis model in antibiotic research.
- To highlight the key parameters and factors investigated using this model.
- To emphasize its ongoing importance in evaluating antibiotic efficacy in vivo.
Main Methods:
- Historical review of the mouse peritonitis model's application in antibiotic research since 1935.
- Discussion of common parameters for measuring antibiotic effect: bacterial counts and animal survival (e.g., 50% effective dose).
- Consideration of host defense modulation to enhance susceptibility to human pathogens.
Main Results:
- The model successfully demonstrated the efficacy of early sulfonamides against Streptococcus pyogenes.
- Numerous significant factors influencing antibiotic effectiveness have been identified and validated using this model.
- The model allows for the assessment of antibiotic effects on bacterial load and host survival.
Conclusions:
- The mouse peritonitis model has a long-standing history and proven track record in antibiotic research.
- Its ability to assess antibiotic efficacy in vivo, combined with new understanding of pharmacokinetic correlations with humans, ensures its continued relevance.
- This model is predicted to remain a vital tool for studying antibiotic effects.