ABSTRACT
A 20-year-old patient, who received a bone marrow transplant in order to treat metachromatic leukodystrophy (MLD), succumbed to cytomegalovirus (CMV) encephalitis. After CMV viremia developed, the patient received ganciclovir, but he was switched to foscarnet when ganciclovir resistance was suspected. Foscarnet was discontinued because of concern about its potential central nervous system toxicity. Autopsy samples of brain and cerebrospinal fluid contained CMV DNA with a UL97 mutation (M460V) known to confer ganciclovir resistance. No foscarnet resistance mutations were found.
Subject(s)
Antiviral Agents/therapeutic use , Bone Marrow Transplantation/adverse effects , Cytomegalovirus Infections/drug therapy , Encephalitis, Viral/drug therapy , Ganciclovir/therapeutic use , Adult , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/pathology , Drug Resistance, Viral , Encephalitis, Viral/etiology , Encephalitis, Viral/pathology , Foscarnet/therapeutic use , Humans , Leukodystrophy, Metachromatic/therapy , MaleABSTRACT
We reviewed 355 autopsies performed between 1990 and 1994 at a major marrow transplant center to determine whether fluconazole prophylaxis prevented visceral fungal infection. Fluconazole prophylaxis was defined by a minimum of 5 prophylactic doses. Fungal infection (any site) was found in 40% of patients transplanted and autopsied at the center. Overall, the proportion of autopsies with any fungal infection was not different for those patients receiving no fluconazole prophylaxis versus those with prophylactic fluconazole. With fluconazole prophylaxis, candidal infections were less frequent, decreasing from 27% to 8%, while Aspergillus infections were more frequent, increasing from 18% to 29%. No increase in deaths related to non-albicans Candida infections was seen. Of the 329 patients with livers examined, hepatic infection caused by Candida species was significantly less common in patients who had received fluconazole. Fungal liver infection was found in 31 patients (9%), 16% of those who were not treated with fluconazole and 3% of those who were treated with fluconazole. Since patients with candidal infections died earlier after marrow transplant than patients with mold infections, we speculate that a longer length of survival may dispose toward acquisition of mold infections. Fluconazole prophylaxis in this cohort of marrow transplant patients undergoing autopsy resulted in a significant reduction in infection caused by Candida species and an increase in mold infections.
