Medical mycology journal最新文献

Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.

Terbinafine (TBF) and azoles are commonly used to treat fungal infections such as tinea pedis and tinea unguium. TBF-resistant Trichophyton species have been increasingly reported globally; however, the research has primarily focused on Trichophyton rubrum. In other words, there are limited studies that exist on other causative Trichophyton species, such as Trichophyton interdigitale, Trichophyton mentagrophytes, and Trichophyton indotineae. This study aimed to determine the prevalence and resistance mechanisms of TBF-resistant Trichophyton isolates in Japan. Screening of 701 clinical isolates preserved at the Medical Mycology Research Center, Chiba University, Japan, identified 20 resistant strains (2.9% prevalence), including 16 T. rubrum, two T. interdigitale, one T. mentagrophytes, and one T. indotineae. Minimum inhibitory concentrations (MICs) to TBF ranged from 1 to ≥ 32 µg/mL. Additionally, strains showing TBF resistance and reduced susceptibility to azoles were identified in T. rubrum, T. mentagrophytes, and T. indotineae. The squalene epoxidase gene sequencing targeted by TBF revealed amino acid mutations, such as Leu393Ser, Leu393Phe, and Phe397Leu in T. rubrum and Ser392Ala and Leu419Phe in other species. Notably, the Phe397 mutation correlated with high MICs (≥ 32 μg/mL), indicating its significant role in TBF resistance. This study detected a novel isolate of T. mentagrophytes showing TBF resistance and reduced susceptibility to azoles. The study underscores the need for ongoing surveillance and monitoring of antifungal resistance patterns for TBF and azole antifungal agents, considering the increasing prevalence of resistant isolates.

Aspergillus sections Flavi, Nigri, and Terrei are known as common causative agents of aspergillosis, followed by section Fumigati. A previous study investigated the distribution of section Fumigati in Izu and Ogasawara Islands and found that the dominant species changes depending on the soil environment. This study investigated the species diversity and distribution of sections Flavi, Nigri, and Terrei in Mukojima, Hahajima, and Chichijima of Ogasawara Islands and clarified whether the dominant species vary depending on the soil environment, as in section Fumigati. The strains were isolated from soil samples collected in 2019 and 2020 at 18 sites in three islands, including different landscapes, and species identification was based on the nucleotide sequence of the calmodulin gene. Overall, 172 strains were isolated from all sites and identified to seven section Flavi, five section Nigri, and three section Terrei species. Three section Flavi, three section Nigri, and one section Terrei species have been reported as causative agents of aspergillosis. Three sections were distributed in Chichijima and Hahajima, but only section Nigri was found in Mukojima. The frequency of occurrence of Aspergillus tamarii and Aspergillus nomiae belonging to section Flavi and Aspergillus niger and Aspergillus tubingensis belonging to section Nigri were > 60% in forests, including shrub forests, whereas that of Aspergillus floccosus belonging to section Terrei was > 40% in bare land and grassland. Aspergillus pseudonomiae belonging to section Flavi was isolated at > 40% frequency of occurrence regardless of the landscape. Thus, differences of soil environments affected the distribution of the dominant species belonging to three sections.

The rapid identification of microbes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is gaining attention, particularly in clinical laboratories and hygiene management in food manufacturing. However, unlike bacteria, technical issues related to preprocessing and a lack of comprehensive reference libraries pose challenges in fungi. In this study, we constructed a new MALDI-TOF MS database, named EMALiMB, that expands the existing reference library to accurately identify a wider range of microbial species. The new reference library included 75 genera and 430 species of Ascomycota, 77 genera and 213 species of Basidiomycota, i.e. a total of 643 species of fungi, and six species belonging to the genus Prototheca. All strains were selected to complement taxa that were either not registered in the current library or were insufficiently represented, owing to a small number of strains. For example, 107 Candida species included pathogens, but also non-pathogenic species, inhabiting in the environment, and phylogenetically closely related with clinical relevants. Additionally, we improved the ionization of basidiomycetous yeasts and filamentous species, and Trichophyton, which had not been sufficiently ionized before, by incorporating bead-crushing in the pretreatment. The accuracy of this new reference library was evaluated using 384 clinical and environmental yeast isolates. A slight but remarkable increase in accuracy from 85.20% to 87.28% and in the mean score from 2.15 to 2.27 was obtained. The coverage rate for tested species improved significantly, from 80% to 88.57% for clinically relevant species, and from 52.38% to 76.19% for species isolated from environments.

We examined 477 patients with culture-positive onychomycosis at the Noguchi Dermatology Clinic between July 2015 and June 2024. Toenail onychomycosis (n = 422) was caused by Trichophyton rubrum (78.0%), Trichophyton interdigitale (19.0%), non-dermatophyte mould (2.8%) and Candida species (0.2%). Fingernail onychomycosis (n = 69) was caused by Candida species (46.4%), T. rubrum (43.5%), T. interdigitale (2.9%), non-dermatophyte mould (4.3%), and Trichosporon species (2.9%). Terbinafine-resistant dermatophyte onychomycosis (n = 17) was caused by T. rubrum (94.1%) and T. interdigitale (5.9%). The prevalence was higher than in the Japanese survey (2.3%), accounting for 6.0% of cases since 2020. Ten mutant strains (58.8%) also showed reduced sensitivity to itraconazole (0.125-0.5 mg/L). These strains were highly sensitive to ravuconazole, efinaconazole, and luliconazole. Fosravuconazole (n = 13) and topical efinaconazole (n = 4) could cure the disease. Non-dermatophyte mould onychomycosis (n = 15) was caused by Aspergillus species (40.0%), Fusarium species (33.3%), Penicillium citrinum, Talaromyces muroii, Botryosphaeria dothidea, and Scopulariopsis brevicaulis (6.7%). When the breakpoint was set to 0.5 mg/L, these strains frequently exhibited resistance to terbinafine (71.4%) and itraconazole (92.9%). Efinaconazole (n = 7) and fosravuconazole (n = 5) were effective in treating these patients. Yeast onychomycosis (n = 35) mainly affected the fingernails (34/35) and was mainly caused by Candida albicans (88.6%). We identified non-albicans Candida species (n = 2), including Candida guilliermondii and Candida parapsilosis. Non-albicans Candida isolates showed low sensitivity to itraconazole and fluconazole. Trichosporon species (n = 2) were isolated from fingernail onychomycosis.

Background: Candida auris is an emerging fungus causing nosocomial infections and outbreaks, with many strains exhibiting multidrug resistance. This study analyzed the C. auris clinical isolates at The Jikei University School of Medicine Kashiwa Hospital from December 2019 to March 2021.

Methods: Clinical data were reviewed retrospectively for patients from whom C. auris was isolated from clinical specimens. Clade analysis and drug susceptibility testing were conducted.

Results: Three strains of C. auris were isolated, all from otorrhea in patients with otitis externa. Case A was a 69-year-old female with aural pain, Case B was an 82-year-old female with left ear deafness, and Case C was a 76-year-old male with left otorrhea and hearing loss; all cases were immunocompetent. Strains from Clade I (South Asian clade) were found in Cases A and C, and a strain from Clade II (East Asian clade) was isolated from Case B. None had a travel history overseas or contact with foreigners. Drug susceptibility testing showed that one C. auris strain of Clade Ⅰ had a high minimal inhibitory concentration for fluconazole. No severe infection was observed, and all cases improved with local treatment, including ketoconazole ointment for Case A.

Conclusion: The presence of Clade I C. auris strains in Japan without travel history raises concerns about domestic or in-hospital transmission. Accurate identification and rigorous infection control are essential to manage the spread of C. auris. Ongoing surveillance, research, and international cooperation are needed.

Dysbiosis of the lung microbiome may be associated with the development and progression of respiratory diseases. As fungal spores invade the lungs more easily than bacteria, it seems likely that fungi colonizing the lungs are also involved in respiratory diseases. In this study, we investigated the relationship between fungal flora (mycobiome) and diffuse lung disease. Of the 185 patients who underwent bronchoalveolar lavage (BAL) during the diagnostic process, 42 with diffuse lung disease were selected for a mycobacterial analysis of BAL fluid. Twenty patients with idiopathic interstitial pneumonia (IIP), 8 with collagen tissue disease-related interstitial lung disease (CTD-ILD), 8 with sarcoidosis, and 6 with other diseases were included. Fungal DNA was extracted, and internal transcribed spacer 2 (ITS2) regions were sequenced. Of the 42 patients, 29 had polymerase chain reaction amplification products in the ITS2 region. Significant differences in alpha diversity (observed species, Shannon, and Simpson indices) were found between the CTD-ILD and sarcoidosis groups, and between the IIP and sarcoidosis groups. A comparison of the mycobiomes of individual patients (beta diversity) showed that the clustering patterns differed among the groups. In particular, BAL fluid samples from patients with sarcoidosis showed a clear clustering pattern of mycobacterial composition. Our results may lead to significant advances in our understanding of the etiology of these diseases.

We describe two clinical features and the fact that Candida auris was isolated from their otorrhea. As a result, antifungal agents were administrated with neither of two cases, and both had favorable clinical outcomes with drainage and antibiotic administration. In our cases, C. auris isolated might not cause inflammation by itself. The feature that both had in common was the presence of serous otorrhea, which distinguished them from conventional other Candida spp.

Aspergillus fumigatus causes fatal infections in immunocompromised individuals, with the increasing number of azole-resistant strains leading to high mortality rates. This study aimed to develop a novel in vitro model using electrical impedance to continuously evaluate interactions between A. fumigatus and human cells and antifungal agent efficacy. A. fumigatus conidia and human cell lines (THP-1 macrophages and A549 alveolar epithelial cells) were cultured. Electrical impedance and fluorescence were observed using the xCELLigence RTCA E-Sight system. Conidia were seeded at various multiplicity of infection (MOI) values, and cell damage was assessed. In addition, the inhibition of cell damage by A. fumigatus in response to antifungal agents was evaluated. The time needed for electrical impedance to fall by half in macrophages was 31.5 hours for MOI 0.1 and 14.1 hours for MOI 8. Therefore, higher conidial concentrations led to faster decreases in electric impedance, indicating increased cytotoxicity. Macrophages showed a gradual decrease in electric impedance with mycelial growth, whereas A549 cells displayed a rapid electric impedance decline after mycelial growth. Azoles and amphotericin B suppressed the electric impedance decrease above their minimum inhibitory concentration, while echinocandins resulted in a continuous electric impedance decrease regardless of concentration. This study demonstrated that electrical impedance constitutes an objective method for continuously evaluating the cytotoxicity of A. fumigatus and antifungal efficacy. This novel in vitro model offers a new standard for studying interactions between filamentous fungi and human cells. Further validation using clinical isolates and other fungi is required.

Gastrointestinal mucormycosis is a rare form of mucormycosis that can potentially result in fatal outcomes. We encountered a case of gastric mucormycosis, first identified at postmortem following the death of a patient with malignant lymphoma. This paper highlights the unique pathological features of this rare gastric mucormycosis, which were suspected to be the primary source of the infection. Additionally, we made a little thought to the potential possibility that unheated vegetables that might be contaminated with the causative fungus could have played as a vector for carrying the fungus into the gastric mucosa.