Pneumocystis pneumonia is the most commonly diagnosed life-threatening opportunistic infection in patients with the acquired immune deficiency syndrome (AIDS). In our experience, the survival of first episodes of PCP was 66.3%, while for patients suffering second episodes it was 25%.
The specific aim of this proposal is to determine if prophylactic treatment with pentamidine can prevent pneumocystis pneumonia in the experimental rat model of the infection. Successful pentamidine chemoprophylaxis in this model would justify trials in humans. Prevention of pneumocystis pneumonia in AIDS patients would greatly reduce morbidity and mortality and would decrease medical costs due to the prolonged hospitalization and intensive supportive care that treatment of the infection requires. Pneumocystis pneumonia can be produced in rats by maintaining them on a low-protein diet and treating them repeatedly with steroids. The infection in this model is usually fatal in eight to twelve weeks. Chemoprophylaxis with pentamidine beginning at week four will be given in a single dose or in four weekly doses, or continuously. The drug will be given by aerosol, intramuscular injection, intravenous infusion, or orally. Results of chemoprophylaxis will be assessed by comparison of survival rates and histopathology of animals that die or are sacrificed. Levels of pentamidine will be measured in tissues of infected and uninfected animals at different times during treatment.
