Invasive Aspergillosis Due toNeosartorya udagawae

Abstract

Background Invasive aspergillosis (IA) is most commonly caused by the morphospecies Aspergillus fumigatus. However, genetic-based methods indicate that organisms phenotypically identified as A. fumigatus actually constitute a mold complex, designated Aspergillus section fumigati subgenus fumigati. Methods Multilocus sequencing and analysis was performed on fungi identified as A. fumigatus from the clinical culture collection maintained at the National Institutes of Health from 2000 through 2008, with a focus on the internal transcribed spacer 1 and 2 regions of ribosomal DNA (rDNA), b-tubulin, and rodlet A genes. We reviewed the medical records, radiology, and histopathology of corresponding patients. To confirm identification of Neosartorya udagawae isolates, mating studies were performed with reference strains. Antifungal susceptibility testing was performed by broth microdilution and read at 48 hours. Results Thirty-six cases of infection attributed to A. fumigatus were identified; 4 were caused by N. udagawae (3 in patients with chronic granulomatous disease and 1 in a patient with myelodysplastic syndrome). Disease due to N. udagawae was chronic, with a median duration of 35 weeks, compared with a median duration of 5.5 weeks for patients with chronic granulomatous disease who had infection due to A. fumigatus sensu stricto (P < .05, Mann-Whitney U test). Infection spread across anatomical planes in a contiguous manner and was refractory to standard therapy. Two of the 4 patients died. N. udagawae demonstrated relatively higher minimum inhibitory concentrations to various agents, compared with those demonstrated by contemporary A. fumigatus sensu stricto isolates. Conclusions To our knowledge, this is the first report documenting infection due to N. udagawae. Clinical manifestations were distinct from those of typical IA. Fumigati-mimetics with inherent potential for antifungal resistance are agents of IA. Genetic identification of molds should be considered for unusual or refractory IA.

Uncommon Neosartorya udagawae Fungus as a Causative Agent of Severe Corneal Infection

“…Minimum effective concentrations (MECs) at 48 h were reported for caspofungin, micafungin, and anidulafungin. According to previous studies (19,25), the isolate was found to be resistant not only to fluconazole (MIC, Ͼ256 g/ml) as expected, but also to voriconazole (8 g/ml), whereas MICs of other antifungal agents demonstrated full susceptibility of the isolate to amphotericin B (0.125 g/ml), itraconazole (0.25 g/ml), and posaconazole (0.25 g/ml). MECs of caspofungin, micafungin, and anidulafungin were 0.5, 0.25, and 0.016 g/ml, respectively.…”

“…Identification of species within a section, e.g., discrimination of A. fumigatus from N. udagawae, may be important given that different species have variable susceptibilities to multiple antifungal drugs (3). Most isolates of A. fumigatus are considered to be susceptible to amphotericin B, extended-spectrum triazoles, and caspofungin (26), whereas Fumigati-mimetic molds, including N. udagawae, tend to demonstrate in vitro resistance to various agents, potentially contributing to refractory disease (25).…”

“…A poly- Although members of the genus Neosartorya present ubiquitously, they have only rarely been reported to be pathogens, perhaps because Aspergillus species with known sexual stages (teleomorphs) tend to produce fewer asexual spores than their nonteleomorphic relatives (9). However, invasive or deep Neosartorya infections involving N. fischeri, N. pseudofischeri, and N. hiratsukae have been described in patients with various underlying diseases, and mortality rates ranged from 33 to 67% (25). Notably, one of these cases involved a patient with no history of trauma to his infected left eye, in whom keratitis progressed to endophthalmitis despite treatment with ketoconazole, thus requiring eye evisceration (6).…”

Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia

“…Subsequently, multiple intracerebral masses with ring enhancement showed invasive mold, and he died of disseminated fungal infection. 18 Patient 13.II.2 was the sister of 13.II.1. She had recurrent infections, including verrucae in childhood, and had been diagnosed with aplastic anemia resulting from leukopenia and thrombocytopenia.…”

Systematic Internal Transcribed Spacer Sequence Analysis for Identification of Clinical Mold Isolates in Diagnostic Mycology: a 5-Year Study

“…We defined a set of criteria and a diagnostic work flow for subjecting isolates to molecular identification. In comparison, available studies mainly reported on nonsystematic approaches analyzing smaller sets of isolates to address a more limited question (1,34,39). The initial phenotypic part of our identification strategy including standard morphological characteristics can be readily adapted to the individual laboratory expertise or could be complemented by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry in the near future (24,32).…”