Managing fungal and viral infection in the immunocompromised host.

Abstract

The increasing number of opportunistic fungal infections in neutropenic cancer patients has become of major concern. Postmortem examinations have shown that more than half of the deaths attributed to infection were due to disseminated fungal infections. Candida species are the major pathogens. Unfortunately, the early diagnosis of serious fungal invasion is exceedingly difficult in these patients, since the manifestations of infection are ill-defined and the organisms can only rarely be isolated from blood cultures. Therefore, empirical antifungal therapy in febrile patients early in the course of disease appears necessary to prevent fungal superinfections and to control clinically undetected fungal invasion. Even if a fungal infection is diagnosed, treatment options are limited to a small number of drugs, and the chance of successful treatment is slim. Amphotericin B remains the most effective drug for systemic fungal infection; however, it is also the most toxic antimicrobical in use. Reduction of its toxicity and, simultaneously, improvement of its effectiveness can be achieved by incorporation into liposomes, although liposomal amphotericin B is not yet available commercially. The newer azoles, such as ketoconazole, vibunazole, and itraconazole are orally active and less toxic. Azoles have been successfully used in the treatment of superficial candidal infections; they are not very active in systemic candidiasis. Inhibitors of the cell wall biosynthesis of candida species include inhibitors of chitin and glucan biosynthesis. Echinocandins and papulacandins interfer with the glucan synthesis and show good anticandidal activity. Their therapeutic potential is currently being explored in clinical trials. Neutropenic patients and particularly bone marrow transplant (BMT) recipients are, in addition to fungal infections, at very high risk for herpesvirus infections: herpes simplex virus (HSV) 0-20 days after BMT, cytomegalovirus (CMV) 40-80 days after BMT, varicella zoster virus (VZV) 100-160 days after BMT, and Epstein-Barr virus (EBV) 14-21 days after BMT. Acyclovir and vidarabine are, at present, the only antiviral drugs available for HSV and VZV infections, acyclovir apparently being the more effective. It is also the drug of choice for prevention of HSV infections in severely immunocompromised, i.e., BMT, patients. Bromovinyldeoxyuridine seems to be suitable for systemic treatment of HSV-1 and VZV infections in these patients. Its potency in inhibiting HSV-1 and VZV replication is superior to that of ACV, and in therapeutic doses it is nontoxic to hematopoietic progenitor cells.(ABSTRACT TRUNCATED AT 400 WORDS)