isavuconazole and Granulomatous-Disease--Chronic

Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease (CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections (IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer (ITS) sequencing. He improved with amphotericin B and isavuconazole but required haematopoietic stem cell transplantation (HSCT). We review the literature on Phellinus infections in CGD and conclude that: (i) these infections emerge on mould-active prophylaxis and are indolent; (ii) they typically cause locally destructive disease but can disseminate; (iii) diagnosis is delayed and requires molecular methods; (iv) amphotericin B is most active in vitro; and (v) treatment is protracted and requires surgery and possibly HSCT. In conclusion, Phellinus spp. are emerging pathogens in CGD. Every effort should be made to establish the diagnosis of non-Aspergillus IFIs in patients with CGD by sending tissue specimens for molecular diagnostics.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Basidiomycota; Brain; DNA, Ribosomal Spacer; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Lung; Male; Nitriles; Pyridines; Tomography, X-Ray Computed; Triazoles; Young Adult

We report the cases of a 39-year-old woman with chronic lymphocytic leukemia and a 21-year-old man with chronic granulomatous disease treated for cerebral aspergillosis. The patients required radical surgery for infection progression despite adequate isavuconazole plasma concentration or neurological complication. We thus decided to measure the brain isavuconazole concentration. These results suggest that the concentrations of isavuconazole obtained in the infected brain tissue clearly differ from those obtained in the normal brain tissue and the cerebrospinal fluid.

Topics: Adult; Aspergillosis; Aspergillus fumigatus; Brain; Cerebrospinal Fluid; Female; Granulomatous Disease, Chronic; Humans; Magnetic Resonance Imaging; Nitriles; Pyridines; Triazoles; Young Adult

Topics: Administration, Oral; Animals; Antifungal Agents; Aspergillosis; Chromatography, Liquid; Disease Models, Animal; Granulomatous Disease, Chronic; Invasive Fungal Infections; Male; Mice; Nitriles; Prodrugs; Pyridines; Tandem Mass Spectrometry; Tissue Distribution; Triazoles