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

Abstract

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.

• Authors: S Kunz, U Junker, J Blaser, B Joos, B Meyer, O Zak, T O'Reilly
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 36 Issue 1 Pg. 137-55 (Jul 1995) ISSN: 0305-7453 [Print] England
• PMID: 8537261 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, drug therapy, microbiology)
• Trimethoprim, Sulfamethoxazole Drug Combination (pharmacokinetics, therapeutic use)