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MRSA PERITONITIS-SEPSIS MOUSE MODEL
Noble Life Sciences, in collaboration with ImQuest Biosciences, has optimized the peritonitis-sepsis mouse model to screen for new antibacterial agents against methicillin-resistant Staphylococcus aureus(MRSA). The model’s popularity derives from its ease of use with small and inexpensive animals, short-duration experiments with reproducible infections, and simple end-points.
The mouse peritonitis-sepsis model, the first animal model for antibiotic research, was used to demonstrate the efficacy of sulphonamides against Streptococcus pyogenes in 1935.
Two models are commonly used as in vivo screens for new antibacterial agents: the neutropenic thigh model and the peritonitis-sepsis model. Noble also has an optimized mouse neutropenic thigh model.
The mouse peritonitis-sepsis model is an important early screening method to study in vivo effects of antibacterial compounds and provides a natural step in testing of antibiotics in vivo before moving to larger animals or humans.
Survival of mice infected with various doses of MRSA was monitored (see figure above).
Survival was dose dependent. All mice which received only the vehicle survived for 7 days. 100% of the mice that received 4 E6 CFU survived for at least 5 days whereas only about 40% of the mice that received 2 E7 CFU survived in this same time period.
Higher doses produced 100% lethality within 24 hours.
Blood samples were collected from mice at various time points post inoculation. Bacterial counts determined by dilution and plating.
Results of analysis of blood samples taken at 2 hours post infection are shown in the figure above. The concentration of bacteria in the blood correlates with the bacterial dose.
Inocula are prepared from a logarithmic phase culture of methicillin-resistant S. aureus by centrifugation and then resuspending the bacteria in hog gastric mucin.
Groups of mice are infected by intraperitoneal injection with the MRSA inoculum. Test agent or vehicle control is administered to screen for efficacy.
- Bacterial Challenge: ATCC strain or client-specified strain
- Reference Substance & Control: Vancomycin (or other reference antibiotic); vehicle
- Length/Endpoint: Two to seven days post infection or per protocol
- Assays & Measurements: Total and differential white blood cell counts; bacterrial counts in blood; body weight; animal observations; PK/PD analyses
We have experience with a variety of mammalian species used for vaccine and drug development. Our studies range from single digit to hundreds of animals.
Our scientists, with over 15 years of GLP experience, provide all aspects of the GLP process from design to regulatory support of your IND, IDE or PMA FDA submission.