Journal of Antimicrobial Chemotherapy (1995) 36, 137-155
© 1995 The British Society for Antimicrobial Chemotherapy
research-article |
The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy
aPharmaceutical Research, Ciba-Geigy Limited Basel, Switzerland, CH-4002 bDepartment of Medicine, University Hospital Zurich, Switzerland, CH-8091
Received 19 July 1994; accepted 31 January 1995
*Corresponding author. Phone +41-(61)-6963427; Fax +41-(61)-6962128.
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, andwas apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of micewith 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 2mg/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.
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