Neutropenia is a condition characterized by an abnormally low number of white blood cells (neutrophils) responsible for the body’s primary defenses against bacteria and other pathogens. Those who are rendered “neutropenic” are more susceptible to bacterial infections and without proper medical attention, this condition may quickly develop into neutropenic sepsis. The murine neutropenic thigh model involves challenging animals with cyclophosphamide, rendering them neutropenic, followed by the injection of a known bacterial pathogen (K. pneumoniae). This model provides a platform in which novel anti-bacterial compounds can be screened for efficacy in the treatment of bacterial infections and sepsis.
Preclinical Drug Efficacy Studies
Animals are administered cyclophosphamide to render them neutropenic. Their thighs are infected intramuscularly with K. pneumoniae. At study completion thighs are harvested and bioburden is measured. The administration of compounds is performed according to the schedule set-forth in the study protocol.
General clinical observations, body weight, white blood cell counts (for Neutropenic status), K. pneumoniae bacterial bioburden counts, cytokine profiling using ELISA and Luminex multiplex assays, flow cytometric analysis for the characterization of inflammatory cells in thigh tissue
Gudmundsson S, Einarsson S, Erlendsdottir H, Moffat J, Bayer W, Craig WA. (1993) The post-antibiotic effect of antimicrobial combinations in a neutropenic murine thigh model. The Journal of Antimicrobial Chemotherapy; 31(Suppl D): 177-91.
Maglio D, Banevicius MA, Sutherland C, Babalola C, Nightingale CH, Nicolau DP. (2004) Pharmacodynamic Profile of Ertapenem against Klebsiella Pneumoniae and Escherichia coli in a Murine Thigh Model. Antimicrobial Agents and Chemotherapy; 49(1): 276-280.
Zuluaga AF, Salazar BE, Rodriguez CA, Zapata AX, Agudelo M, Vesga O. (2006) Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases. BMC Infectious Diseases; 6(55): 1471-2334.