Rhino-sino-orbital and/or central nervous system infections due to Lomentospora prolificans and Scedosporium spp. in onco-haematology patients.

Abstract

Lomentospora prolificans and Scedosporium spp. are emerging non-Aspergillus moulds causing invasive fungal disease (IFD) in onco-haematology patients. Rhino-sino-orbital and/or central nervous system (CNS) infections are poorly described yet associated with high mortality. We aimed to characterize clinical, microbiological, treatment, and outcome features of rhino-sino-orbital and/or CNS infections due to these moulds in an onco-haematology population. We retrospectively reviewed proven/probable IFD patients with rhino-sino-orbital and/or CNS involvement from 2010 to 2024 caused by L. prolificans and Scedosporium spp. at two Australian tertiary centres in adults with cancer. Eighteen episodes were analysed; 94.5% had haematological malignancy, mainly acute myeloid leukaemia (41.5%), and 53% were haematopoietic stem cell transplant recipients. Lomentospora prolificans predominated (83%) and displayed intrinsic resistance to conventional antifungals. Olorofim showed potent in vitro activity when tested (n = 5, MIC 0.125-0.5 mg/l). Disseminated disease occurred in 78%, mainly affecting lung (79%), CNS (64%), and eye (43%). Initial combination therapy with a voriconazole and terbinafine-including regimen was used in 87.5% and surgery in 50%; olorofim was administered to five patients. Overall mortality was high: 56% at 30-day and 67% at 180-day follow-up, with early death noted if there was CNS involvement (70%). Lower 30-day and 180-day mortality was observed in localized rhino-sino-orbital and Scedosporium spp. infections (0% and 20%, respectively), particularly when surgery and olorofim were used. Our results underline the high mortality from L. prolificans infections in onco-haematology patients with disseminated disease or CNS involvement. Early aggressive surgery and novel antifungals may improve outcomes, but prospective multicentre studies are needed to define optimal treatment strategies.