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Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients.The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Marañón [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non—transplant recipients with scedosporiosis who were described in the literature.Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P =.045), to have an earlier onset of infection (P =.007), to be neutropenic (P <.0001), and to have fungemia (P =.04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P =.002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P =.08). Presence of disseminated infection (OR, 0.20; P =.03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P =.02) independently predicted a better survival in this model.Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.