Breakthrough Hormographiella aspergillata Infections Arising in Neutropenic Patients Treated Empirically with Caspofungin

Abstract

Hormographiella aspergillata, a filamentous basidiomycete, has rarely been involved in human infections. We describe 2 febrile neutropenic patients who developed a severe pulmonary infection due to H. aspergillata while receiving empirical caspofungin therapy for presumed fungal pneumonia. After introduction of liposomal amphotericin B, one patient, who had neutrophil recovery, presented a favorable outcome, while the other, who remained neutropenic throughout the course of infection, died. Resistant fungi, including basidiomycetes, may emerge during empirical treatment with caspofungin in febrile neutropenic patients. A rapid switch to any other potent antifungal should be rapidly considered in case of failure of caspofungin in this setting. CASE REPORTSCase description for patient 1. A 23-year-old female was diagnosed with biphenotypic acute leukemia. She received induction chemotherapy associating idarubicine, high-dose cytarabine, and corticosteroids. Because of her persistent fever while receiving large-spectrum antibiotics for febrile neutropenia, empirical caspofungin was added (70 mg on day 1, followed by 50 mg daily thereafter). Fever persisted, and she developed a dry cough and scapular pain on day 23. Serum galactomannan antigen (GMA) was repeatedly negative, and blood cultures were sterile. A chest X-ray showed an upper right lobe infiltrate, and a computed tomography (CT) scan demonstrated a nodular infiltrate surrounded by a halo sign. Caspofungin was replaced after 20 days by voriconazole (400 mg per day) for possible pulmonary aspergillosis. Despite hematological recovery and complete remission, a control CT scan on day 36 showed a progression of the lung infiltrate. A transthoracic percutaneous puncture of the lesion was performed under CT scan guidance and showed the presence of rare septated hyphae under direct microscopic examination (Fig. 1). After 13 days of voriconazole, antifungal therapy was then changed to liposomal amphotericin B starting at 5 mg/kg of body weight/day, and the patient's condition improved, with a marked reduction of the pulmonary infiltrate. Liposomal amphotericin B was then reduced to 5 mg/kg on alternate days because of severe hypokalemia. Consolidation chemotherapy was delayed for 2 weeks because of uncontrolled infection, during which time she received oral treatment with 6-mercaptopurine and etoposide. She then proceeded to the consolidation phase and received three courses of chemotherapy before undergoing myeloablative conditioning and syngeneic stem cell transplantation from her twin sister 7 months later. Hematological recovery occurred on day 15. During neutropenia, she was maintained on liposomal amphotericin at 5 mg/kg/day until day 45, when all antifungal treatment was discontinued (total duration of liposomal amphotericin B, 8 months). Three years after stem cell transplantation, she is alive and cured from her invasive fungal infection.Case description for patient 2. A 27-year-old male with adult-onset X-linked adrenoleukodystrophy characterized by adren...

Clinical Significance of Filamentous Basidiomycetes Illustrated by Isolates of the Novel Opportunist Ceriporia lacerata from the Human Respiratory Tract

“…Possibly the shelf fungi, naturally being involved in lignin degradation, have only limited virulence, whereas with the ruderal mushrooms Coprinus cinereus and V. volvacea, a higher degree of invasive potential may be expected. This is evident from a high case fatality (73%) in invasive infections due to C. cinereus reported in 8 of the 11 patients of hematological malignancies described in literature so far (10,25,27,28,35,36,37). Also, a solitary fatal case of V. volvacea in a patient following double umbilical cord blood transplantation has been reported (18).…”

“…has been shown to be involved in the formation of a secondary pulmonary fungal ball but not in invasive disease (4). In contrast, recurrent invasive infections, in addition to pulmonary colonization, are observed with the members of Agaricales, Hormographiella aspergillata and Hormographiella verticillata (5,6,(8)(9)(10)(25)(26)(27)(28), and in V. volvacea (18). These mushrooms have a ruderal strategy (29), colonizing compost, dung, self-heated wood chips, and similar substrates.…”

Clinical Significance and Molecular Characterization of Nonsporulating Molds Isolated from the Respiratory Tracts of Bronchopulmonary Mycosis Patients with Special Reference to Basidiomycetes

“…In the past 2 decades, filamentous basidiomycetes have been reported as invasive pathogens in immunosuppressed patients, such as patients with hematological malignancies, patients with neutropenia, and solid-organ transplant recipients (3)(4)(5)(6)(17)(18)(19)(20). However, the true clinical significance of white cottony NSMs in pulmonary mycoses is poorly understood (8).…”

“…Identification of such fungi in specific clinical settings has a favorable impact on patient management and therapeutic outcomes (1,2). The filamentous basidiomycetes include a substantial number of NSMs that may be resistant to antifungals (3)(4)(5)(6). Nonsporulating filamentous basidiomycetes such as Hormographiella aspergillata and Volvariella volvacea are resistant to amphotericin B (AMB), caspofungin (CAS), itraconazole (ITC), voriconazole (VRC), and posaconazole (POS) and have been associated with high case fatality rates in the past (3)(4)(5)7).…”

“…The filamentous basidiomycetes include a substantial number of NSMs that may be resistant to antifungals (3)(4)(5)(6). Nonsporulating filamentous basidiomycetes such as Hormographiella aspergillata and Volvariella volvacea are resistant to amphotericin B (AMB), caspofungin (CAS), itraconazole (ITC), voriconazole (VRC), and posaconazole (POS) and have been associated with high case fatality rates in the past (3)(4)(5)7). Although filamentous basidiomycetes are being increasingly recognized in clinical specimens, their definitive identification using conventional methods can be problematic (8,9).…”