Fungal infections in the immunocompromised host

Abstract

Invasive fungal infections cause significant morbidity and mortality in patients with impaired immune defences. Defects in neutrophil function and neutropenia predispose to disseminated Candida, Aspergillus and Mucoraceae infections while altered T-lymphocyte mononuclear phagocyte function predisposes to infection with C. neoformans, Histoplasma and Coccidioides. Fungal infections in the immunocompromised host are difficult to diagnose and difficult to treat successfully. The diagnosis is often missed or delayed because of the non-specific clinical features, the failure to isolate or difficulty in interpreting the presence of the fungus from routine microbiological cultures, and the limited usefulness of available serological tests. The assay for cryptococcal antigen is the only currently available reliable serological test used to diagnose an invasive fungal infection. Definitive diagnosis is made by histopathological demonstration of the fungus in tissue or a positive culture from a sterile body site. Invasive procedures are often necessary to obtain adequate tissue for histology and culture. The treatment of invasive fungal infection in the immunocompromised host is amphotericin B with or without 5FC. The usual recommended dose is 1.5 to 3 g total amphotericin B over 6 to 12 weeks. The optimal dose and duration of therapy for each infection is not known. Treatment failures and relapses are common in patients who do not achieve remission of their underlying disease. Ketoconazole, a new broad-spectrum oral antifungal medication, does not appear to be effective therapy for invasive fungal infection in the immunocompromised patient based on results of small clinical trials. New diagnostic methods and therapeutic approaches are necessary to improve the outcome of these infections. Areas of current research include serological assays for fungal antigens and metabolites which may allow earlier diagnosis, treatment with combinations of antifungal agents, and the development of new antifungal agents.