We report two cases of invasive infections due to Geosmithia argillacea, an emerging mold, in patients with chronic granulomatous disease receiving prolonged azole antifungal prophylaxis. One patient died despite receiving a combination of four antifungals, and the other developed cerebral and medullary lesions under a combination of caspofungin, posaconazole, terbinafine, and gamma interferon.
CASE REPORTSPatient 1. A 14-year-old girl with chronic granulomatous disease (CGD; autosomal recessive form implying the CYBA gene encoding subunit p22 phox ) was admitted to Nancy University Hospital (Nancy-F) for allogeneic peripheral blood stem cell transplantation using a matched unrelated donor. Her medical history included a prior undocumented granulomatous pulmonary mass requiring lobectomy in 2006. She received a primary antifungal prophylaxis, with 200 mg voriconazole twice a day (b.i.d.) from the day of grafting. On day 43 postgraft, she developed acute grade II graft-versus-host disease, requiring methylprednisolone. On day 60, galactomannan was detected in serum, and a computed tomography (CT) scan revealed a T1 spondylodiscitis with a paravertebral abscess. Liposomal amphotericin B (3 mg/kg of body weight per day), combined with caspofungin (70-mg loading dose, followed by 50 mg daily), was initiated. A biopsy of the paravertebral abscess was performed. Microscopic examination of histological sections stained with periodic acid-Schiff stain, hematoxylin-eosin, and Gomori methenamine silver revealed branching, septate hyphae, and many vesicular swellings of different sizes (Fig. 1A). Cultures of the biopsy specimen (isolate 1) rapidly grew brownish colonies on Sabouraud agar at 30°C. The microscopic morphology, with penicillate conidiophores attached to hyaline septate hyphae, resembled that of a Penicillium species. On day 143, she had a persistent cough with dyspnea and fever and received empirical antibiotics. On day 198 postgraft, she experienced a seizure, and cerebral magnetic resonance imaging (MRI) revealed disseminated cerebellar and cerebral abscesses. A cerebral biopsy was not performed. She subsequently received terbinafine (250 mg b.i.d.) and then flucytosine (6 g/day) in addition to liposomal amphotericin B and caspofungin but died on day 258 postgraft.Patient 2. A 30-year-old patient with X-linked recessive CGD was admitted in March 2010 at the Centre d'Infectiologie Necker-Pasteur (Paris-F) with bilateral pulmonary infiltrates (Ն4 cm) and a thoracic subcutaneous abscess with local rib lysis.He previously experienced relapsing otitis media and Mycobacterium bovis adenitis. He also had developed 3 prior episodes of invasive aspergillosis, the latest being in May 2009 and related to Aspergillus nidulans, for which he received voriconazole. Subsequently, he was transiently colonized by Penicillium chermesinum and Scopulariopsis brevicaulis (both confirmed by internal transcribed spacer [ITS] sequencing). Bronchoalveolar lavage fluid culture and biopsy of the subcutaneous lesion revealed septate hyp...
