The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy

J Antimicrob Chemother. 1995 Jul;36(1):137-55. doi: 10.1093/jac/36.1.137.


The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

MeSH terms

  • Animals
  • Anti-Infective Agents / therapeutic use*
  • Antifungal Agents / therapeutic use
  • Blood Cell Count
  • Body Fluids / metabolism
  • Dose-Response Relationship, Drug
  • Lung / microbiology
  • Mice
  • Mice, SCID / microbiology*
  • Organ Size / drug effects
  • Pentamidine / therapeutic use
  • Pneumonia, Pneumocystis / blood
  • Pneumonia, Pneumocystis / drug therapy*
  • Pneumonia, Pneumocystis / microbiology
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacokinetics
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use


  • Anti-Infective Agents
  • Antifungal Agents
  • Pentamidine
  • Trimethoprim, Sulfamethoxazole Drug Combination