Neutropenic Mouse Thigh Model of Infection 2018-05-24T10:57:40+00:00

THE SMART SOLUTION FOR

PRECLINICAL DEVELOPMENT

NEUTROPENIC MOUSE THIGH MODEL OF INFECTION

SERVICE DESCRIPTION

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.

APPLICATIONS

  • 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)

METHODOLOGY

Cotton rats are infected intranasally under light anesthesia with the influenza virus. The time course of the infection is followed by determining viral titers in nasal or lung tissue homogenates or in bronchoalveolar fluid (BALF).  

The efficacy of test agents in animals challenged with the virus is determined at peak viral titers.

Viral titers are determined via plaque assay or qPCR. H&E stained sections of lung tissue can be prepared for evaluation of tissue histology. 

OPTIONS

  • Drug Administration Route: Intranasal, intravenous, intramuscular, continuous infusion

  • Reference Substance & Control: Anti-influenza agents or other reference vehicle

  • Length/Endpoint: Five to seven days post infection

  • Assays & Measurements:  Viral load in nasal tissue, viral load in BALF, viral load in lung homogenate, immunohistochemistry, tissue pathology, cytokine levels

APPLICATIONS

  • Vaccine & antiviral drug development
  • Test adenoviral vector-based gene therapies
  • Study infectious disease pathogenesis
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Proven Expertise

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.

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