Extensive primary cutaneous fusariosis in a patient with burns: A case report and review of the literature.

BACKGROUND: Fusarium species can cause a broad spectrum of human infections, ranging from superficial and locally invasive to disseminated, depending on the immune status of the host and portal of entry. Although several cases of cutaneous fusariosis in burn victims have been reported, molecular identification for pathogen recognition has been used only in a few cases. CASE DESCRIPTION: In this report, we describe an uncommon case of extensive primary cutaneous fusariosis caused by Fusarium keratoplasticum in a patient who sustained injuries during stubble burning. FINDINGS: A review of cases of cutaneous fusariosis in burn victims revealed that this uncommon infection could be lethal, and treatment strategies should focus on both surgical debridement and the initiation of systemic antifungal therapy. Furthermore, because skin defects can serve as a portal of entry for Fusarium species in burn victims, early and aggressive treatment is crucial to prevent serious consequences.

Clinical manifestations and susceptibility of Scedosporium/Lomentospora infections at a tertiary medical centre in Taiwan from 2014 to 2021: A retrospective cohort study.

BACKGROUND: Scedosporiosis/lomentosporiosis is a globally emerging and crucial fungal infection. However, clinical data on Scedosporium/Lomentospora infections in Taiwan are scarce. OBJECTIVES: This study aimed to explore the clinical characteristics of Scedosporium/Lomentospora-infected patients and evaluate the susceptibility of these isolates to antifungal agents. METHODS: The clinical features of Scedosporium/Lomentospora-infected patients at a tertiary teaching hospital in Northern Taiwan between 2014 and 2021 were retrospectively reviewed; isolates from these patients were identified to species level for antifungal susceptibility testing. RESULTS: Among 44 patients, 27 (61.4%) had scedosporiosis/lomentosporiosis, whereas 17 (38.6%) were colonised with Scedosporium/Lomentospora species. Scedosporium apiospermum was the main coloniser; scedosporiosis was primarily caused by S. boydii. Trauma history, steroid and immunosuppressant use were the most common risk factors for developing these infections. Among 27 patients with scedosporiosis/lomentosporiosis, one was lost to follow-up and seven (7/26, 26.9%) died. Most patients with S. apiospermum infection have a history of trauma, leading to cutaneous, bone and ocular infections. Pulmonary, sinus and disseminated infections and mortality were frequently reported in patients with S. boydii infection. Voriconazole's minimum inhibitory concentration was low for S. boydii, S. apiospermum and S. aurantiacum. Caspofungin, micafungin and anidulafungin were active against S. boydii and S. apiospermum. A potentially novel Scedosporium species was identified in this study, with distinct clinical manifestations and antifungal susceptibility. CONCLUSIONS: At our centre, S. boydii is the main causative species of scedosporiosis; voriconazole could be the first-line treatment in Taiwan. Our study supports the importance of speciation, rather than only categorising these isolates into S. apiospermum species complex.

Nannizzia polymorpha as Rare Cause of Skin Dermatophytosis.

Nannizzia polymorpha is a dermatophyte that rarely infects humans. We describe 2 case-patients from Asia who had an inflammatory type of tinea capitis and tinea manuum caused by infection with this fungus. The diagnosis was confirmed on the basis of the morphologic and molecular characteristics of the microorganism.

High Diversity of Fusarium Species in Onychomycosis: Clinical Presentations, Molecular Identification, and Antifungal Susceptibility.

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium's native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study's primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp.

Cutaneous infection caused by Purpureocillium lilacinum: Case reports and literature review of infections by Purpureocillium and Paecilomyces in Taiwan.

Hyalohyphomycosis is a rare infection caused by a group of fungi that are devoid of pigments in their cell walls. As one of the main pathogens of hyalohyphomycosis, Purpureocillium lilacinum (former Paecilomyces lilacinus) is known for its intrinsic resistance to various antifungal agents. Here, we report three cases that coincide with a history of farming and all of them suffered from cutaneous hyalohyphomycosis caused by P. lilacinum. They shared a clinical presentation consisting of erythematous-to-violaceous painful plaques with overlying pustules on one of their forearms. Hyphae and fungal elements were highlighted by periodic acid Schiff or Gomori methenamine silver staining in their skin biopsies. Fungal cultures of their skin tissues yielded P. lilacinum, which was confirmed by both morphological and molecular characteristics. All patients responded well to oral terbinafine or itraconazole treatment. In this report, we also reviewed previously reported cases associated with either P. lilacinum or other Paecilomyces spp. infections in Taiwan.

The high diversity of Scedosporium and Lomentospora species and their prevalence in human-disturbed areas in Taiwan.

Scedosporium and Lomentospora are important opportunistic pathogens causing localized or disseminated infection in humans. Understanding their environmental distribution is critical for public hygiene and clinical management. We carried out the first environmental survey in urbanized and natural regions in Taiwan. Overall, Scedosporium and Lomentospora species were recovered in 132 out of 273 soil samples (48.4%) across Taiwan. We morphologically and molecularly identified six Scedosporium and one Lomentospora species. All four major clinical relevant species were isolated with high frequency, i.e., Scedosporium apiospermum (42.4%), S. boydii (21.8%), Lomentosporaprolificans (14.5%), S. aurantiacum (8.5%); two clinically minor species, Pseudallescheria angusta (6.7%) and S. dehoogii (5.6%), and a saprobic species, S. haikouense (0.6%), had moderate to rare incidence. These fungal species had high incidence in urban (48.6%) and hospital (67.4%) soil samples, and had limited distribution in samples from natural regions (5%). Multivariate analysis of the fungal composition revealed strong evidence of the preferential distribution of these fungi in urban and hospital regions compared with natural sites. In addition, strong evidence suggested that the distribution and abundance of these fungal species were highly heterogeneous in the environment; samples in vicinity often yielded varied fungal communities. We concluded that these fungal species were prevalent in soil in Taiwan and their occurrences were associated with human activities. Although, hygiene sensitive sites such as hospitals were not harboring heavier fungal burdens than other urban facilities in our survey, still, aware should be taken for the high frequency of these clinical relevant species around hospital regions.

Scedosporium and Lomentospora are two fungal genera that can cause infections to wildlife and humans. Our experiment demonstrated that these fungi are ubiquitous in the soil in Taiwan. Their proximity to human-dwelling regions raises our awareness of their exposure to those who are susceptible.

Azole Resistance and cyp51A Mutation of Aspergillus fumigatus in a Tertiary Referral Hospital in Taiwan.

Azole resistance in Aspergillus fumigatus has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in cyp51A. The objective of this study was to test the antifungal susceptibilities of A. fumigatus isolates from Chang Gung Memorial Hospital (CGMH), the largest tertiary referral hospital in Taiwan, and to investigate cyp51A mutations in azole-resistant strains. A. fumigatus isolates preserved in the Research Laboratory of Medical Mycology of CGMH from 2015 to 2021 were used. Antifungal susceptibility testing was performed using the YeastOneTM method. Isolates with high minimal inhibitory concentrations (MICs) against antifungals were further tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Mutations in the cyp51A in azole-resistant strains were detected by Sanger sequencing. The overall prevalence of azole-resistant isolates was 1.77% (two out of 113 isolates). The two azole-resistant strains had tandem repeats (TR) in the promoter region and mutations in the cyp51A gene (TR34/L98H and TR34/L98H/S297T/F495I). One strain showed intermediate susceptibility to voriconazole, and its Cyp51A protein had five amino acid substitutions (F46Y/M172V/N248T/D255E/E427K). TR34/L98H and TR34/L98H/S297T/F495I are the most prevalent cyp51A mutations in Taiwan, mediating azole resistance based on current publications and our results. YeastOneTM was validated as a rapid tool for the antifungal susceptibility test; however, further confirmation by CLSI should be considered when MIC values of voriconazole, posaconazole, and amphotericin B are close to the clinical breakpoints or ecological cutoff values.

Fusarium Keratitis in Taiwan: Molecular Identification, Antifungal Susceptibilities, and Clinical Features.

We performed molecular identification and antifungal susceptibilities of pathogens and investigated clinical features of 43 culture-proven Fusarium keratitis cases from 2015-2020 in Taiwan. The pathogens were identified by sequencing of their internal transcribed spacer regions of ribosomal DNA and translation elongation factor 1α gene; their antifungal susceptibilities (to seven agents) were determined by broth microdilution method. We also collected clinical data to compare the drug susceptibilities and clinical features of Fusarium solani species complex (FSSC) isolates with those of other Fusarium species complexes (non-FSSC). The FSSC accounted for 76.7% pathogens, among which F. falciforme (32.6%) and F. keratoplasticum (27.9%) were the most common species. Among clinically used antifungal agents, amphotericin B registered the lowest minimal inhibitory concentration (MIC), and the new azoles efinaconazole, lanoconazole and luliconazole, demonstrated even lower MICs against Fusarium species. The MICs of natamycin, voriconazole, chlorhexidine, lanoconazole, and luliconazole were higher for the FSSC than the non-FSSC, but no significant differences were noted in clinical outcomes, including corneal perforation and final visual acuity. In Taiwan, the FSSC was the most common complex in Fusarium keratitis; its MICs for five tested antifungal agents were higher than those of non-FSSC, but the clinical outcomes did not differ significantly.

Annular infectious dermatoses.

Annular configuration is conspicuous in the clinical manifestation of many skin diseases and can be helpful for the diagnosis and differential diagnosis. Variations may include arciform, ring-form, annular, circinate, serpiginous, gyrated, polycyclic, targeted or figurate forms, in different colors, sizes, and numbers, with various textures and surfaces. In infectious dermatoses, the annular reactions can be specific or nonspecific, while the underlying mechanisms remain largely unknown. In the specific reactions caused by direct invasion of the pathogens, the contest between the centrifugal outspread of the infectious agents and the centripetal impedance of the host immune response is supposed to determine the final conformation. Examples include erythema infectiosum, orf, erythema multiforme, and pityriasis rosea of viral origin. Bacterial infections that may display annular lesions include erythrasma, erythema (chronicum) migrans of Lyme borreliosis, secondary syphilis, cutaneous tuberculosis, and leprosy. Superficial mycosis, such as dermatophytosis, candida intertrigo, tinea imbricata, and subcutaneous mycosis, such as chromoblastomycosis, and algae infection protothecosis, are characterized by annular progression of the skin lesions. The creeping serpiginous extension is an alarming sign for the diagnosis of cutaneous larva migrans. A better understanding of the virulence and pathogenicity of the pathogens and the way and type of immune response will help to clarify the pathogenesis.

Infection with Nannizziopsis guarroi and Ophidiomyces ophiodiicola in reptiles in Taiwan.

Fungal infection is an emerging threat to reptiles. The main pathogens are fungi of the genera Nannizziopsis, Paranannizziopsis and Ophidiomyces. The clinical symptoms range from mild skin lesions to the dissemination of internal organs and even death. Most of the reported cases are from Europe, North America and Australia. In this study, we report the Nannizziopsis guarroi infection in one captive inland bearded dragon (Pogona vitticeps), one captive green iguana (Iguana iguana) and Ophidiomyces ophiodiicola infection in one wild red-banded snake (Dinodon rufozonatum) and one wild Chinese cobra (Naja atra) in Taiwan. The infections were confirmed by the presence of fungal elements in the tissue. The pathogens were identified based on their morphological and DNA sequence characteristics. The susceptibility profiles of the fungal strains to nine antifungal drugs were obtained using broth microdilution methods. The presence of both fungal species in Asia highlights the urgent need for surveillance and close monitoring of reptile infections to prevent them from spreading and to the possible collapse of reptile populations in the wild.

Disseminated Fungal Infection and Fungemia Caused by Trichosporon asahii in a Captive Plumed Basilisk (Basiliscus plumifrons).

Trichosporon spp. are heavily arthroconidiating fungi and widely distributed in nature. Due to the similar fungal morphology, confusion among Trichosporon spp., Geotrichum spp., and Nannizziopsis spp. in reptiles is apparent and cannot be overlooked. Although few reptile Trichosporon isolates have been examined using the newer speciation criteria, the information on Trichosporon asahii in reptiles is still scarce. In the present study, we report the case of disseminated fungal infection and fungemia caused by T. asahii in a captive plumed basilisk (Basiliscus plumifrons). Multiple 0.2-0.5 cm, irregularly shaped, ulcerative nodules on the left hind foot were observed. The animal died due to the non-responsiveness to treatment. A microscopic evaluation revealed the fungal infection that primarily affected the left hind foot and right lung lobe with fungal embolisms in the lung and liver. The molecular identification of the fungal species by the DNA sequences of the ITS regions and D1/D2 gene from the fungal culture and ITS regions, from formalin-fixed paraffin-embedded (FFPE) lung tissues, were completely matched to those of T. asahii. The current report describes the first confirmed case of disseminated fungal infection and fungemia caused by T. asahii in a captive plumed basilisk.

Disseminated Candidiasis and Candidemia Caused by Candida palmioleophila in a Green Sea Turtle (Chelonia mydas).

A sub-adult green sea turtle (Chelonia mydas) was rescued and treated for carapace and plastron shell fractures. The turtle was kept dry-docked for the first 2 months with a placement of a long-term jugular central venous catheter (CVC). Pain management, aggressive antibiotic and anthelmintic therapy, fluid therapy, force feeding, and wound debridement were provided to manage the shell fractures and control bacteremia. Human albumin was administered to treat severe hypoalbuminemia. On day 59, small budding yeasts were noted on the blood smears. Candidemia was confirmed by blood culture, as the yeasts were identified as Candida palmioleophila by the molecular multi-locus identification method. The CVC was removed, and the patient was treated with itraconazole. Although the carapace and plastron wounds had epithelized by 5.5 months after the rescue, the turtle died unexpectedly by 7.5 months. The postmortem examination revealed numerous necrogranulomas with intralesional yeasts, morphologically compatible with Candida spp., in joints, bones, brain, and lungs, suggestive of disseminated candidiasis. We describe a rare case of candidemia in the veterinary field. To our knowledge, this is the first report of candidiasis caused by C. palmioleophila in a reptile. The present results should improve veterinary medical care and, therefore, enhance the conservation of endangered sea turtle species.

Fusarium solani species complex infection in elasmobranchs: A case report for rough-tail stingray with valid antifungal therapy.

Fusarium species are common plant and animal pathogens. For humans, there are two dominant species complexes, F. solani species complex (FSSC) and F. oxysporum species complex (FOSC), which both infect immunocompromised individuals. However, there are few reports related to elasmobranchs infected by Fusarium species. In this study, we report a case of a rough-tail stingray from an ocean park infected by FSSC diagnosed using histopathology and microscopic observation, with morphological characteristics and molecular techniques used to identify the pathogen. Histopathology showed fungal hyphae invading stingray tissues, while micro/macroconidia were found under the microscope. We identified this pathogen as FSSC 12 through phylogenetic analysis using internal transcribed spacer (ITS) and elongation factor 1-alpha (EF1-α) sequences. Furthermore, we report that application of voriconazole (orally) and terbinafine (topically) constituted an effective therapy, curing the stingray.

Deep cutaneous fungal infection by Pleosporales: An exceptional pathogen in tropical Taiwan.

Deep cutaneous fungal infections (DCFI) are cutaneous and subcutaneous infectious diseases caused by fungi. Multiple genera of pathogenic fungi have been reported to cause DCFI. Herein, we report three rare cases of Pleosporales deep cutaneous infection in a southern Taiwan medical center. We evaluated the clinical manifestations, histopathological findings, pathogens, treatments and outcomes. The patients were a 77-year-old woman, a 78-year-old woman and an 81-year-old man, who lived in rural tropical areas. The lesions were erythematous noduloplaques with dark spots located on the upper extremities. Sequence-based identification showed three different fungi of the order Pleosporales, namely Nigrograna mackinnonii, Medicopsis romeroi and Parathyridaria percutanea. All three cases received 200 mg of oral itraconazole daily for 10, 2 and 8 months, respectively. Two of them are free of diseases to date, and one improved partially but did not complete the treatment. Molecular tools are helpful for the identification of DCFI to exact species, which is key to successful treatment.

Clinical and epidemiological characteristics of tinea capitis in northern Taiwan during 2014-2019: An unusual bimodal distribution of patients and comparison of paediatric and adult cases.

Tinea capitis (TC) mainly occurs in children, and related studies in adults are rare. We aimed to investigate the current epidemiological, clinical and mycological characteristics of TC and to compare adult and paediatric patients in northern Taiwan. We conducted a retrospective study at Chang Gung Memorial Hospital, Linkou Branch, from 2014 to 2019. The dataset included age, sex, records of underlying diseases, animal contact history, frequent hair salon visits, clinical patterns, treatment and outcome via chart or phone call reviews. The average ages of 72 children and 104 adults recruited were 6.0 and 74.0 years, respectively. A female predominance was noted in both groups, and the ratio of females was significantly higher in adults (94.2% vs 59.7%, P < .0001). Microsporum canis (76.4%) and Trichophyton mentagrophytes (11.1%) in children, and M. canis (49.0%) and T. violaceum (31.7%) in adults were the most common pathogens. Adults were more likely to be infected with T. violaceum (OR = 10.14, 95% CI = 2.04-50.26) than children. In contrast, adults were less likely to be infected with M. canis than children (OR = 0.31, 95% CI = 0.11-0.90). Furthermore, adults visited hair salons more, had less animal contact and were more immunosuppressed than children. TC is not unusual in the adult population. Dermatologists are advised to realise risk factors such as immunosuppression and regular hair salon visit in adult TC.

Correction: Colonization of human opportunistic Fusarium oxysporum (HOFo) isolates in tomato and cucumber tissues assessed by a specific molecular marker.

[This corrects the article DOI: 10.1371/journal.pone.0234517.].

Filamentous Fungal Keratitis in Taiwan: Based on Molecular Diagnosis.

Purpose: To analyze the epidemiological pattern, demographics, risk factors, and treatment outcomes of filamentous fungal keratitis at a tertiary hospital in Taiwan. Methods: We recruited 65 patients (65 eyes) with culture-proven filamentous fungal keratitis who received diagnosis and treatment at Chang Gung Memorial Hospital between 2015 and 2018. All isolates were examined through conventional morphological identification and subjected to molecular identification with internal transcribed spacer sequencing. Data on patient demographics, predisposing factors, and treatment outcomes were collected. Results: In total, filamentous fungi belonged to 16 genera were identified. Fusarium spp. (29 cases [44.6%]) was the most commonly isolated organism overall, followed by Colletotrichum spp. and Purpureocillium linacinum (seven cases [10.8% for each]), and Aspergillus spp. (six cases [9.2%]). Some fungi that have not been regarded as human pathogens were also identified, such as Paracremonium and Phellinum. Among 52 (80%) patients with predisposing factors, 30 (46.2%) had trauma. The ulcers of 33 (50.8%) patients resolved with medical treatment only. Additionally, six patients (9.2%) had corneal perforation, and nine patients (13.9%) required therapeutic/destructive surgical interventions including therapeutic penetrating keratoplasty (seven patients) or evisceration (two patients). Only 16 patients (24.6%) had final visual acuity of 20/40 or better. Conclusions: Through molecular diagnosis, a high diversity of fungal pathogens was revealed along with an increasing incidence of Colletotrichumspp. and Purpureocilliumspp. in Taiwan. The most common risk factor for filamentous fungal keratitis was trauma. The visual outcomes were guarded. Translational Relevance: The molecular diagnosis provides insight into accurate identification, which affects the epidemiology and diversity of pathogens of filamentous fungal keratitis.

Histopathology, Molecular Identification and Antifungal Susceptibility Testing of Nannizziopsis arthrosporioides from a Captive Cuban Rock Iguana (Cyclura nubila).

Chrysosporium-related fungi, the cause of superficial and deep mycoses, are an emerging infectious disease affecting not only reptiles but also immunocompromized humans. However, the information on Nannizziopsis arthrosporioides is extremely scarce. We herein characterized N. arthrosporioides isolated from a Cuban rock iguana (Cyclura nubila). Three skin ulcers were found in a Cuban rock iguana after captivity for 8 years. Microscopic examination revealed hyperplastic, hyperkeratotic, and ulcerative dermatitis coupled with numerous branched, septate fungal hyphae. The fungal culture yielded growth of zonate, felted cottony-powdery colonies with lobate margins on medium. Maximum-likelihood phylogeny tree based on the combined partial actin and partial ß-tubulin genes demonstrated that current isolates were mostly close to N. arthrosporioides. Furthermore, antifungal susceptibility test demonstrated that N. arthrosporioides had lowest minimal inhibitory concentration (MIC) values to isavuconazole, efinaconazole, and luliconazole, which may be the potential treatment of choice for N. arthrosporioides infection. The current study describes the first confirmed case of dermatomycosis caused by N. arthrosporioides of a captive reptile in Asia with detailed descriptions of the clinical, histopathological, and mycological features. The current findings provide new information on global distribution and host range of N. arthrosporioides and can raise the concern on the transboundary or emerging disease of N. arthrosporioides in Asian region.