Failure of Pentamidine Isethionate to Provide Chemoprophylaxis against Pneumocystis carinii Infection in Rats

Abstract

Latent Pneumocystis carinii infections were exacerbated in 54 adult male Sprague-Dawley rats by administration of alternating subcutaneous doses of hydrocortisone-21-phosphate and of cortisone acetate three times a week, plus 0.5% chlortetracycline in their drinking water, until death or the termination of the experiment at 120 days. Twenty-eight of the rats were also given pentamidine isethionate (4 mg/kg) intramuscularly daily for 14 days. Pentamidine-treated animals that died within the 120 days of the experiment survived longer than control animals. At necropsy, however, every animal in both groups had P. carinii in the lungs. The intensity of the infection was the same in the pentamidine-treated and control groups. Pentamidine isethionate administered in this standard regimen does not exert a significant chemoprophylactic effect against proliferation of P. carinii in rats. The study provides little encouragement for use of pentamidine as a prophylactic agent against P. carinii in high-risk patients.