Scedosporium prolificans, a mold morphologically similar to Scedosporium apiospermum, may cause asymptomatic colonization or localized or disseminated infection following trauma, surgery, and immunosuppression. S. prolificans is normally resistant to available antifungal agents, and prognosis depends largely on the host's immune status, extent of infection, and feasibility of surgical debridement. We report on 16 patients with deep S. prolificans infections, focusing on predisposing factors, clinical characteristics, outcome, postmortem findings, and antifungal susceptibility testing to 6 antifungal agents. Between 1989 and 1994, 16 cases of deep infections by S. prolificans were documented in 6 clinical centers in Spain (15 adults and 1 child: male/female = 0.77). Fifteen patients had underlying hematologic malignancy (14 with neutropenia) and 1 had a prosthetic cardiac valve. Syndromes included disseminated infection in 14 patients (1 with prosthetic valve endocarditis) and fungal pneumonia and meningoencephalitis in 1 patient each. S. prolificans was isolated from 2 specimens in 14 patients and from 1 specimen in 2 patients (blood, n = 12; respiratory tract, n = 4; CNS, n = 4; and skin biopsy, n = 3). Antifungal susceptibility testing by a micromethod with RPMI-2% glucose medium was performed in 8 isolates, all of which were resistant to amphotericin B, flucytosine, ketoconazole, fluconazole, itraconazole, and miconazole. All patients received antifungal therapy (amphotericin B, n = 9; amphotericin B+ flucytosine, n = 1; amphotericin B+ itraconazole, n = 2; liposomal amphotericin B+ itraconazole, n = 1; amphotericin B+ fluconazole, n = 1 and 2 underwent surgical procedures. Two patients survived coinciding with hematologic recovery and 14 (87.5%) patients died in a median time of 4 days after the first positive culture (range, 0-60 d). Necropsy was performed in 10 patients, and disseminated infection was found in 9. In conclusion, S. prolificans is an emerging multiresistant fungal pathogen that may cause asymptomatic colonization, localized infection related to trauma or surgery, and rapidly fatal disseminated infection in immunocompromised hosts, particularly those with neutropenia. This mycosis underscores the urgent need for new antifungal agents.

SummaryThe malignant, CD5 + B lymphocytes of B cell chronic lymphocytic leukemia (B-CLL) die by apoptosis in vitro. This is in contrast to the prolonged life span of the leukemic cells in vivo and likely reflects the lack of essential growth factors in the tissue culture medium. We found that interferon 3~ (IFN-3~) inhibits programmed cell death and promotes survival of B-CLL cells in culture. This effect may also be important in vivo: increased serum levels of IFN-% ranging from 60 to >2,200 pg/ml, were found in 7 of 10 B-CLL samples tested, whereas the sera of 10 healthy individuals did not contain detectable levels of this cytokine (<20 pg/ml). High levels of IFN-'y message were detected in RNA from T cell-depleted B-CLL peripheral blood samples by Northern blot analysis. Synthesis of IFN-3' by B-CLL lymphocytes was confirmed by in situ hybridization and flow cytometry. The majority of B-CLL cells (74-82%) expressed detectable levels of IFN-~/mRNA, and CD19 + B-CLL cells were labeled with anti-IFN-3, monoclonal antibodies. These results show that IFN-'y inhibits programmed cell death in B-CLL cells and suggest that the malignant cells are able to synthesize this cytokine. By delaying apoptosis, IFN-~/ may extend the life span of the malignant cells and thereby contribute to their clonal accumulation.