We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed.
CASE REPORTA 37-year-old woman suffering from cystic fibrosis (CF) was admitted to our institution in April 2008 for double-lung transplantation. Her medical history included diabetes mellitus since 2002 and more than 10 years of airway colonization with Aspergillus fumigatus and Scedosporium/Pseudallescheria. Starting in 2006, and while awaiting transplantation, she received oral voriconazole (250 mg, twice a day). Her postoperative course was relatively uncomplicated except for cytomegalovirus (CMV) infection due to a mismatch at the time of transplantation in spite of valganciclovir prophylactic treatment (900 mg/day). The immunosuppressive regimen included tacrolimus (therapeutic range, 12 to 13.5 ng/ml), mycophenolate mophetil (750 mg/day), and prednisone (37.5 mg/day). Oral voriconazole was continued as a long-term posttransplantation prophylaxis (250 mg twice a day). A fungal culture of a bronchial secretion obtained the day after transplantation was positive for a filamentous fungus routinely identified as Scedosporium apiospermum/P. boydii (isolate I), but several other respiratory specimens obtained over the following weeks were negative. The patient was discharged from the hospital on day 45 after transplantation, still taking voriconazole. The voriconazole serum levels, checked regularly (1.06, 1.96, and 1.69 mg/liter on days 26, 36, and 50, respectively) were within therapeutic limits (1 to 2.5 mg/liter) except for two occasions (0.16 and 0.35 mg/liter on days 18 and 64, respectively).In June (day 70), she presented at our hospital with nodules on her legs that had appeared 2 weeks previously. On examination, the nodules were fibrous, dermo-hypodermic, measuring 1 to 2 cm in diameter, and slightly pigmented on the surface. A biopsy was performed. Histopathological microscopic examination (Gomori-Grocott and periodic acid-Schiff stainings) revealed an inflammatory infiltrate along with several branched and septate hyaline hyphae (fungal cultures were not performed). Continuation of voriconazole in association with a reduced dose of corticosteroid was associated with clinical improvement. However, 3 weeks later, a new biopsy was performed and septate hyphae were again seen on direct examination. A fungal culture of this biopsy specimen was positive for S. apiospermum/P. boydii (isolate II). At this time, the results for chest computed tomography (CT) were unremarkable, no sign of dissemination was noted on brain CT, and the nodules disappeared over the following weeks.All the while, positive CMV DNAemia was still detected in spite of successive curative treatments with per os valganciclovir (1,800 mg/day fro...