Neutropenic Mouse Thigh Model of Infection
The neutropenic mouse thigh model of infection is a platform for the in vivo study of antibacterial agents under conditions optimal for efficacy, i.e., neutropenia. Because the pharmacology of antimicrobial agents is affected by the presence of neutrophils, animals are rendered neutropenic with the immunosuppressive agent, cyclophosphamide.
- Comparison of antimicrobial agents and dosing regimens
- Determination of PK/PD indices related to efficacy (and prevention of emergence of resistance) of an antimicrobial agent.
- Determination of the time course of antimicrobial activity - concentration or time dependent; presence/absence of persistent effects
- Identification of factors that affect the magnitude of PK/PD indices – CFU changes (short course of therapy) vs survival (long course of therapy)
- Determination of dose, dosing interval, and susceptibility breakpoints
- Testing/benchmarking antimicrobial drugs; determination of therapeutic equivalence of generic products
Results of vancomycin treatment in neutropenic mice challenged with Staphylococcus aureus (Groups 2-7); group 1 was not inoculated. Following the bacterial challenge, mice were treated with either vehicle or vancomycin. Dose is total over a 24-hour period administered at 2, 8, and 14 hours post inoculation. The mice were sacrificed 24-hr post inoculation (Groups 1, 3-7) or 2-hr post inoculation (Group2); the total CFU/gram of thigh was measured for each group (n=3).