403. Prognostic Factors in 260 Adults With Invasive Scedosporiosis From Literature and FungiScope™

BACKGROUND: Invasive scedosporiosis (iS) and lomentosporiosis (iL) are an increasing concern due to intrinsic resistance of such pathogens to antifungal therapy. Guidelines recommend voriconazole, amphotericin B and surgery to treat scedosporiosis, irrespective of the causative species. Scedosporium spp. are often resistant to amphotericin B but susceptible to posaconazole and voriconazole, whereas Lomentospora prolificans (LoPro) is usually pan-resistant. Mortality rates rise to 90%, despite comprehensive treatment. Here, we describe the epidemiology of iS/L. METHODS: A retrospective analysis of patients with iS/iL was conducted to evaluate clinical characteristics and outcomes. Cases diagnosed from January 2000 until August 2017 were selected from the literature and the FungiScope™ registry. In vitro susceptibility to approved and new antifungals was determined according to EUCAST and CLSI methods. RESULTS: We identified 208 cases with infection caused by Scedosporium spp. and 56 by LoPro. iS was most frequently reported in patients after solid organ transplantation (27.9%), iL in patients with underlying malignancy (51.9%). Skin, lung, CNS, and eye were most frequently involved in iS cases, whereas involvement of lung, eye, and blood stream infection were most common in iL cases. Posaconazole and voriconazole showed good in vitro activity against most Scedosporium spp. isolates, but not LoPro. The new antifungal drug Olorofim was highly active against all isolates tested in vitro, also LoPro. All-cause mortality in Scedosporium spp. cases ranged from 12.5% in trauma patients to 55.2% in patients with malignancy, in the LoPro group from 28.6% in surgical patients to 85.2% in patients with malignancy. In iS cases worse outcome was associated with disseminated disease and CNS involvement in transplant recipients, and lung involvement in patients with malignancy. In iL cases, malignancy and fungemia were associated with worse outcome. CONCLUSION: Clinical presentation and outcome vary between iS and iL cases. Blood stream infection and CNS involvement are associated with worse outcome. Activity of Olorofim against Scedosporium spp. and LoPro will be evaluated in an upcoming phase III trial. DISCLOSURES: J. Vehreschild, Merck / MSD: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Gilead: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Pfizer: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Astellas Pharma: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Basilea: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Deutsches Zentrum für Infektionsforschung: Member, Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium Uniklinik Freiburg / Kongress und Kommunikation: Speaker’s Bureau, Speaker honorarium. Akademie für Infektionsmedizin: Speaker’s Bureau, Speaker honorarium. Universität Manchester: Speaker’s Bureau, Speaker honorarium, Deutsche Gesellschaft für Infektiologie: Member and Speaker’s Bureau, Speaker honorarium. Ärztekammer Nordrhein: Speaker’s Bureau, Speaker honorarium. Uniklinik Aachen: Speaker’s Bureau, Speaker honorarium. Back Bay Strategies: Speaker’s Bureau, Speaker honorarium. Deutsche Gesellschaft für Innere Medizin: Member and Speaker’s Bureau, Speaker honorarium. M. J. G. T. Vehreschild, Pfizer: Speaker’s Bureau, Speaker honorarium. MSD/Merck: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Gilead Sciences: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Organobalance: Speaker’s Bureau, Speaker honorarium Astellas Pharma: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. 3M: Research Contractor, Research grant. DaVolterra: Research Contractor, Research grant. Berlin Chemie: Consultant, Consulting fee O. A. Cornely, Amplyx Pharmaceuticals, Basilea Pharmaceutica, F2G, Gilead Sciences, MSD Sharp and Dohme, Scynexis Inc.: Consultant, Consulting fee Amplyx Pharmaceuticals, Basilea Pharmaceutica, F2G, Gilead Sciences, MSD Sharp and Dohme, Scynexis Inc.: Grant Investigator, Research grant Basilea Pharmaceutica, Gilead Sciences, MSD Sharp and Dohme, Pfizer: Speaker’s Bureau, Speaker honorarium