Our studies are devoted to developing methods to define patients at high risk for infection, improving the ability to diagnose infection, improving the ability to diagnose infections early, treat them effectively and ultimately prevent them. We are seeking to those granulocytopenic patients who are at heightened risk for infection. We are developing new therapeutic approaches based on new antibiotic developments, particularly the third generation cephalosporins. Our results show that a new cephalosporin, ceftazidime, is as effective as a triple drug combination. Our studies are also defining the appropriate antibiotic therapy for documented bacterial infections, the necessary duration of empiric therapy for patients with unexplained fever, the choice of empiric antifungal therapy, and the merits of empiric therapy vs invasive procedures in patients with pulmonary infiltrates. To prevent infections we are continuing our study of total protected isolation for high risk patients but are developing new prevention strategies to improve host defenses. These include passive immunization with post-vaccine antisera to the core glycolipid of enterobacteriaceae as well as pooled immunoglobulins. Our preclinical studies are further focused on attaching (arming) leukocytes with polyclonal or monoclonal antibodies to improve their bactericidal activities and ultimately leukocyte transfusion therapy. We are evaluating the effect of various opiate derivatives on leukocyte function and we are developing experimental animal models to help elucidate current clinical delemmas -- e.g., invasive fungal infections in neutropenic patients.
