Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice

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Abstract
A simple, reproducible model of fatal P. aeruginosa sepsis in mice during immunosuppression was developed. Mice were rendered leukopenic (.ltoreq. 800 leukocytes/mm3 of blood) for 5 days by multiple injections of cyclophosphamide. Mice were challenged at the onset of leukopenia by instilling the bacteria onto a 0.5 mm incision made into the back. The LD50 for P. aeruginosa PA220 and M-2 was < 20 bacteria. The mean time to death for these strains was 46-59 h. Leukopenic mice were comparatively resistant when challenged with Klebsiella pneumoniae (LD50 = 1.5 .times. 106) or Staphylococcus aureus (LD50 > 106). Infection with P. aeruginosa was characterized by rapid bacterial multiplication in the skin at the site of infection, producing ecthyma gangrenosum. Bacteremia and colonization of the liver were pronounced 21 h postinfection. This model should prove to be a useful tool for studying the pathogenesis of P. aeruginosa infections under immunosuppressed conditions.