Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.

Terbinafine-Resistant Dermatophytes and the Presence of Trichophyton indotineae in North America.

Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton interdigitale. Outbreaks of recalcitrant dermatophytosis have been reported in parts of South Asia, including those caused by a hypervirulent and resistant species, Trichophyton indotineae. We evaluated the antifungal susceptibility profiles of dermatophytes received by our laboratory from institutions across North America between 2021 and 2022 and performed species identification for isolates deemed to demonstrate in vitro resistance. Susceptibility testing was performed by CLSI broth microdilution methods, and species identification was performed by DNA sequence analysis. During this 2-year period, 271 dermatophyte isolates were included, the majority of which demonstrated low MIC values for terbinafine (geometric mean [GM] and modal MIC, 0.031 µg/mL and 0.008 µg/mL, respectively) and the azoles itraconazole, posaconazole, and voriconazole (0.035 to 0.049 µg/mL and ≤0.03 µg/mL). However, 18.6% of the isolates tested were resistant to terbinafine (MIC ≥ 0.5 µg/mL), including 21 T. rubrum and 21 T. indotineae isolates. These isolates were received from several different states in the United States and two provinces in Canada. In contrast, resistance to itraconazole was relatively rare. We also searched our laboratory database for earlier isolates that were resistant to terbinafine and identified 3 additional T. indotineae isolates, the earliest of which was from 2017. These results demonstrate that terbinafine resistance in dermatophytes was relatively common over this 2-year period and that T. indotineae is present in multiple areas in North America. Continued surveillance is warranted.

Rigidoporus corticola Colonization and Invasive Fungal Disease in Immunocompromised Patients, United States.

We report 2 cases of Rigidoporus corticola (Oxyporus corticola) infection in humans in the United States. Clinical manifestations consisted of angioinvasive fungal sinusitis in 1 patient and pulmonary intracavitary fungus ball in the other patient. These cases illustrate previously undescribed clinicopathologic manifestations of infection by this filamentous basidiomycete in humans.

Three-gene phylogeny of the genus Arthroderma: Basis for future taxonomic studies.

Arthroderma is the most diverse genus among dermatophytes encompassing species occurring in soil, caves, animal burrows, clinical material and other environments. In this study, we collected ex-type, reference and authentic strains of all currently accepted Arthroderma species and generated sequences of three highly variable loci (ITS rDNA, ß-tubulin, and translation elongation factor 1-α). The number of accepted species was expanded to 27. One novel species, A. melbournense (ex-type strain CCF 6162T = CBS 145858T), is described. This species was isolated from toenail dust collected by a podiatrist in Melbourne, during an epidemiological study of four geographical regions of Eastern Australia. Trichophyton terrestre, Chrysosporium magnisporum, and Chrysosporium oceanitis are transferred to Arthroderma. Typification is provided for T. terrestre that is not conspecific with any of the supposed biological species from the former T. terrestre complex, that is, A. insingulare, A. lenticulare and A. quadrifidum. A multi-gene phylogeny and reference sequences provided in this study should serve as a basis for future phylogenetic studies and facilitate species identification in practice. LAY ABSTRACT: The genus Arthroderma encompasses geophilic dermatophyte species that infrequently cause human and animal superficial infections. Reference sequences from three genetic loci were generated for all currently accepted Arthroderma species and phylogeny was constructed. Several taxonomic novelties are introduced. The newly provided data will facilitate species identification and future taxonomic studies.

Retrospective study of phaeohyphomycosis in aquarium-housed fish, with first descriptions of Exophiala lecanii-corni and Neodevriesia cladophorae in fish.

A broadening fish host range is affected by novel and known pigmented fungal pathogens. A review of 2,250 piscine submissions received by the Aquatic Pathology Service, University of Georgia, revealed 47 phaeohyphomycosis cases (2.1%), representing 34 bony and cartilaginous fish species. The majority involved bony fish (45/47, 95.7%) and were predominantly marine (41/47, 87.2%), with only a few freshwater species (4/47, 8.5%). Cartilaginous fish cases included two zebra sharks (Stegostoma fasciatum) (2/47, 4.3%). Northern seahorses (Hippocampus erectus) had the highest incidence overall (7/47, 14.9%). Culture and sequencing of the internal-transcribed spacer region of the rDNA (ITS), large ribosomal subunit gene D1/D2 domains (LSU) and the DNA polymerase II gene (RPB2) were performed for fungal identification when fresh tissue was obtainable. Exophiala, Ochroconis and Neodevriesia spp. were identified, with Exophiala as the most common fungal genus (8/11, 72.7%). Exophiala lecanii-corni and Neodevriesia cladophorae were described for the first time from fish. Microscopically, lesions were characterized by necrosis, granulomatous inflammation and angioinvasion most frequently affecting the skin/fin, skeletal muscle and kidneys. In this study of diverse aquarium-housed fish species, phaeohyphomycosis cases occurred sporadically and in rare outbreaks with variable pathologic presentations, tissue distributions and severities.

Nanopore Sequencing of the Fungal Intergenic Spacer Sequence as a Potential Rapid Diagnostic Assay.

Fungal infections are being caused by a broadening spectrum of fungi, yet in many cases, identification to the species level is required for proper antifungal selection. We investigated the fungal intergenic spacer (IGS) sequence in combination with nanopore sequencing for fungal identification. We sequenced isolates from two Cryptococcus species complexes, C. gattii and C. neoformans, which are the main pathogenic members of this genus, using the Oxford Nanopore Technologies MinION device and Sanger sequencing. There is enough variation within the two complexes to argue for further resolution into separate species, which we wanted to see if nanopore sequencing could detect. Using the R9.4.1 flow cell, IGS sequence identities averaged 99.57% compared to Sanger sequences of the same region. When the newer R10.3 flow cell was used, accuracy increased to 99.83% identity compared to the same Sanger sequences. Nanopore sequencing errors were predominantly in regions of homopolymers, with G homopolymers displaying the largest number of errors and C homopolymers displaying the least. Phylogenetic analysis of the nanopore- and Sanger-derived sequences resulted in indistinguishable trees. Comparison of average percent identities between the C. gattii and C. neoformans species complexes resulted in only a 74 to 77% identity between the two complexes. Sequencing using the nanopore platform could be completed in less than an hour, and samples could be multiplexed in groups as large as 24 sequences in a single run. These results suggest that sequencing the IGS region using nanopore sequencing could be a potential new molecular diagnostic strategy.

Phialophora chinensis fungal keratitis: An initial case report and species identification.

Purpose: To report the initial case of microbial keratitis caused by Phialophora chinensis, a rare cause of fungal keratitis. Observations: A 66-year-old gentleman with a complex right eye (OD) ocular history including herpes simplex virus infectious epithelial keratitis with subsequent neurotrophic keratopathy, and prior combined Candida albicans and parapsilosis fungal keratitis presented with pain OD in the absence of an antecedent trauma. The patient was found to have a filamentous fungal keratitis, which was subsequently cultured and identified as Phialophora chinensis by the laboratory. Despite topical and oral antifungal treatment based on sensitivities determined by the lab, the patient ultimately required intrastromal and subconjunctival antifungal injections, corneal crosslinking, and superficial keratectomy with amniotic membrane to clinically improve. The fungal keratitis recurred twice, with each occurrence rapidly progressing to corneal perforation. Months after the second penetrating keratoplasty, the patient's mental status declined due to multiorgan failure. An occult pulmonary malignancy was discovered during this hospital stay, and the patient was lost to follow-up after entering hospice. Conclusions and Importance: We report a unique case of fungal keratitis caused by Phialophora chinensis and the subsequent management, including both medical and surgical interventions. Despite a multimodal treatment regimen, this case demonstrates the recalcitrant and potentially recurrent nature of fungal keratitis caused by P. chinensis.

Systemic Exophiala equina infection in an Eastern box turtle (Terrapene carolina carolina): a case report and literature review.

Phaeohyphomycosis is an infection caused by melanized fungi. This disease has been reported in several animal species including invertebrates, cold-blooded vertebrates, mammals, and humans. Melanized fungi have similar phenotypical features and confirmation requires culture and molecular diagnostics. To exemplify this we present a case of a 333 g adult of unknown age, free-ranging, male Eastern box turtle (Terrapene carolina carolina) that was referred to the Turtle Rescue Team at North Carolina State University for evaluation of multilobulated masses occupying the entire left orbit and at the right forelimb on the plantarolateral aspect of the foot. A fine needle aspirate cytologic examination of the mass on the right forelimb revealed large numbers of inflammatory cells and fungal organisms. Histopathology of the skin biopsies from the right forefoot was consistent with phaeohyphomycosis. A course of antifungal medication was started (Fluconazole 21 mg/kg loading dose IV then 5 mg/kg PO SID q 30 days). Due to concern for the patient's quality of life and the lack of a curative treatment plan, humane euthanasia was elected. Gross and histological postmortem examination confirmed the presence of multiple coelomic masses similar in appearance to those observed in the left orbit and right forefoot indicating disseminated phaeohyphomycosis. A swab of the periocular mass was submitted for fungal culture and phenotypic identification. The isolate was later identified as Exophiala equina through a combination of phenotypic characterization and sequencing of the ITS region of the nuclear rDNA. Exophiala is a genus in the family Herpotrichiellaceae, order Chaetothyriales and is considered an opportunistic "black yeast" causing infection in aquatic invertebrates, fish, amphibians, reptiles, and mammals including humans. Exophiala equina is infrequently reported in animals, with only three cases in the literature including the herein report.

Species Distribution and Antifungal Susceptibilities of Aspergillus Section Terrei Isolates in Clinical Samples from the United States and Description of Aspergillus pseudoalabamensis sp. nov.

Aspergillus section Terrei consists of numerous cryptic species in addition to A. terreus sensu stricto. The treatment of invasive infections caused by these fungi may pose a unique challenge prior to diagnosis and species identification, in that they are often clinically resistant to amphotericin B, with poor outcomes and low survival rates in patients treated with this polyene. Data on the species distributions and susceptibility profiles of isolates within section Terrei from the United States (U.S.) are limited. Here, we report the species distributions and susceptibility profiles for amphotericin B, isavuconazole, itraconazole, posaconazole, voriconazole, and micafungin against 278 clinical isolates of this section from institutions across the U.S. collected over a 52-month period. Species identification was performed by DNA sequence analysis and phenotypic characterization. Susceptibility testing was performed using the CLSI broth microdilution method. The majority of isolates were identified as Aspergillus terreus sensu stricto (69.8%), although several other cryptic species were also identified. Most were cultured from specimens collected from the respiratory tract. Posaconazole demonstrated the most potent activity of the azoles (MIC range ≤ 0.03-1 mg/L), followed by itraconazole (≤0.03-2 mg/L), voriconazole, and isavuconazole (0.125-8 mg/L for each). Amphotericin B demonstrated reduced in vitro susceptibility against this section (MIC range 0.25-8 mg/L), although this appeared to be species-dependent. A new species within this section, A. pseudoalabamensis, is also described. Our results, which are specific to the U.S., are similar to previous surveillance studies of the Aspergillus section Terrei.

Phaeohyphomycosis due to Exophiala in Aquarium-Housed Lumpfish (Cyclopterus lumpus): Clinical Diagnosis and Description.

Phaeohyphomycosis caused by Exophiala species represents an important disease of concern for farmed and aquarium-housed fish. The objective of this study was to summarize the clinical findings and diagnosis of Exophiala infections in aquarium-housed Cyclopterus lumpus. Clinical records and postmortem pathology reports were reviewed for 15 individuals from 5 public aquaria in the United States and Canada from 2007 to 2015. Fish most commonly presented with cutaneous ulcers and progressive clinical decline despite topical or systemic antifungal therapy. Antemortem fungal culture of cutaneous lesions resulted in colonial growth for 7/12 samples from 8 individuals. Amplification of the internal transcribed spacer region (ITS) of nuclear rDNA identified Exophiala angulospora or Exophiala aquamarina in four samples from three individuals. Postmortem histopathologic findings were consistent with phaeohyphomycosis, with lesions most commonly found in the integument (11/15), gill (9/15), or kidney (9/15) and evidence of fungal angioinvasion and dissemination. DNA extraction and subsequent ITS sequencing from formalin-fixed paraffin-embedded tissues of seven individuals identified E. angulospora, E. aquamarina, or Cyphellophora sp. in four individuals. Lesion description, distribution, and Exophiala spp. identifications were similar to those reported in farmed C. lumpus. Antemortem clinical and diagnostic findings of phaeohyphomycosis attributable to several species of Exophiala provide insight on the progression of Exophiala infections in lumpfish that may contribute to management of the species in public aquaria and under culture conditions.