Medical mycology最新文献

Fungal infections affect 2% of Malaysia's population, yet little is known about mycology laboratory practices in the country. This study surveyed 48 medical institutions, including 14 state hospitals, 26 major specialist hospitals, 4 minor specialist hospitals, 3 university hospitals, and 1 reference laboratory, to assess current practices and identify areas for improvement. Nearly all hospitals performed germ tube testing for Candida albicans (87.5%, 42/48). Yeast identification was conducted using API® (52%, 25/48) or VITEK® (52%, 25/48), with two institutions employing both methods. Advanced methods like matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) were used in only 39.6% (19/48) of institutions, while PCR and DNA sequencing (6.3%, 3/48 each) were limited to university and reference labs. Mould identification primarily relied on the tease mount method (91.7%, 44/48), indicating widespread capability for morphological identification. Antifungal susceptibility testing for yeast was available in all hospitals except minor specialist hospitals, using VITEK® (35.4%, 17/48), Sensititre® (20.8%, 10/48), or Etest® (8.3%, 4/48). Serology testing focused on opportunistic mycoses, particularly Cryptococcus spp. (50.0%, 24/48), while testing for endemic pathogens like Histoplasma was rare (2.1%, 1/48). Aspergillosis testing was limited to galactomannan enzyme immunoassay and lateral flow assay (6.3%, 3/48 each), and no institutions performed (1,3)-beta-d-glucan testing. While advanced diagnostics were available in state and major hospitals, minor specialist hospitals lacked access. These findings highlight the urgent need to enhance laboratory infrastructure, expand access to advanced diagnostics like MALDI-TOF, and train personnel to improve fungal infection management in Malaysia.

The Candida parapsilosis complex, consisting of C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis, is a major cause of Candida onychomycosis. Increasing reports of high levels of resistance to antifungal drugs, particularly fluconazole and echinocandin, have raised concerns about C. parapsilosis complex. This study investigates antifungal resistance and hydrolytic enzyme activity in these species. Species were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and internal transcribed spacer (ITS) 1-4 sequencing. Antifungal susceptibility was assessed using Sensititre™ YeastOne™. Hydrolytic enzyme production was assessed by agar plate culture. Among 43 isolates, C. parapsilosis sensu stricto was most prevalent (48.8%, n = 21/43), followed by C. orthopsilosis (39.6%, n = 17/43) and C. metapsilosis (11.6%, n = 5/43). All C. parapsilosis sensu stricto isolates were susceptible to antifungal agents, except 4.8% (n = 1/21) showing dose-dependent susceptibility to fluconazole and 4.8% (n = 1/21) resistance to amphotericin B. Candida orthopsilosis showed significant resistance to fluconazole and voriconazole (52.9% each, n = 9/17), posaconazole (23.5%, n = 4/17), and low resistance to amphotericin B (5.9%, n = 1/17). One C. metapsilosis isolate (20%) showed cross-resistance to fluconazole and voriconazole, and another (20%) was resistant to 5-flucytosine. Enzymatic assays showed higher protease and lipase activity in C. parapsilosis sensu stricto and C. orthopsilosis compared to C. metapsilosis, with C. parapsilosis sensu stricto showing the highest protease activity. Comprehensive research into antifungal susceptibility and virulence factors of the C. parapsilosis species complex is essential to monitor the growing threat of antifungal resistance and to better understand its role in onychomycosis pathogenesis.

Burns are among the most devastating traumatic injuries. The primary risk of infection stems from disruption of the primary barrier, the skin. For patients with deep burns, loss of the dermis is the main risk factor for systemic bacterial and fungal infections, which occur in 70% and 20%-25% of cases, respectively. Meanwhile, viral infections occur in 5%-10% of cases. Fungal infections are associated with mortality rates ranging from 33% to 60%. This study is a retrospective, cross-sectional analysis conducted at the Centro Nacional de Investigación y Atención de Quemados at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra in Mexico City. The study examined all fungi recovered from biopsies of burn patients from July 2011 to July 2023. A total of 63 cases were included, predominantly flame burns (77.78%), with Fusarium spp. (53.97%) as the predominant fungal genus associated with infection, followed by Aspergillus spp. (19.04%). Most patients had third-degree burns, and the mean total body surface area burned was 46.2%. This study aims to describe the epidemiology and distribution of mold infections in a tertiary care center for burn patients in Mexico City from July 2011 to July 2023.

Cryptococcus gattii is a fungal pathogen that poses significant threats to human health, affecting both immunocompromised and immunocompetent individuals. Treatment of C. gattii infections typically involves the use of antifungal agents, such as azoles. However, the increasing emergence of antifungal resistance in C. gattii is a growing concern, highlighting the critical need for novel therapeutic strategies. In our previous study, we identified a mitochondrial ATP-binding cassette (ABC) transporter, Atm1, as potentially involved in antifungal resistance in C. gattii through transcriptome sequencing, but its function remains unclear and requires additional confirmation and investigation. In this study, we developed a "suicide" clustered regularlyinterspaced short palindromic repeats-CRISPR-associated protein 9 system in C. gattii, based on the system used in C. neoformans, and successfully validated its functionality by targeting the ADE2 gene. We subsequently generated C. gattii mutants lacking ATM1 and assessed their growth under various stress conditions. Our data suggest that Atm1 is involved in the iron-sulfur cluster biosynthesis process. Besides, disruption of ATM1 resulted in various growth impairments, including reduced stress tolerance, impaired capsule formation, and diminished virulence. Importantly, we observed compromised antifungal drug resistance in the atm1∆ mutant and performed RNA sequencing-based transcriptome analysis and gene ontology analysis with and without antifungal treatment for further investigation. In conclusion, our findings indicate that ATM1 plays a role in iron homeostasis and is critical for antifungal resistance in C. gattii, offering new insights into potential drug development strategies for the clinical treatment of cryptococcosis.

Following the complete relaxation of Corona Virus Disease 2019 (COVID-19) epidemic control measures in China by the end of 2022, the number of patients with pulmonary mycosis admitted to hospitals across the country has exhibited a more pronounced upward trend. However, statistical data is lacking to determine whether there is a significant correlation between COVID-19 and pulmonary mycosis. This study collected baseline information, the first laboratory indicators after admission, the types of pathogens, and the prognosis data of patients with pulmonary fungal infections from a tertiary hospital in northern Anhui Province from January 1, 2017, to December 31, 2023, to reveal any association between COVID-19 infection and pulmonary fungal infections. The research results indicated that the G and GM test levels of patients who recovered from COVID-19 and those currently experiencing active infection with COVID-19 were significantly higher than those of patients with pulmonary fungal infections who had never been infected with COVID-19. Infection with COVID-19 and other viruses (excluding COVID-19), mechanical ventilation, and concurrent solid tumors were identified as independent risk factors for poor prognosis in patients with pulmonary fungal diseases. Among patients with viral infections, COVID-19 infection was the most common, with 25 cases (41.67%), followed by herpes simplex virus infection, with 15 cases (25.00%).

Chromoblastomycosis (CBM) is a chronic fungal infection caused by dematiaceous fungi. In some cases, culture methods fail to identify the fungal species, and fresh tissue for molecular identification is unavailable. The use of molecular techniques on formalin-fixed, paraffin-embedded (FFPE) samples can aid in identifying the causative agent. This study aimed to identify fungal species in histopathologically confirmed cases of CBM using PCR and sequencing of 18S-ITS1-5.8S-ITS2-28S rDNA region of FFPE skin biopsies and to describe their clinicopathological features. This retrospective study used FFPE samples from nine CBM patients from remote regions of Mexico. The samples were submitted to the Mycology Section at the Hospital General "Dr. Manuel Gea González" (2000-2016) for molecular identification of the causative agent and characterization of clinicopathological features. Lesions were most commonly located on the forearm (four cases), with one case each on the buttock, back, foot, and leg. One patient presented with cutaneous dissemination. Verrucous plaques were observed in 88.9% of cases. Histology and direct examination confirmed CBM, showing muriform cells and varying degrees of dermal fibrosis in all cases. DNA extracted from FFPE samples was amplified and sequenced in the 18S-ITS1-5.8S-ITS2-28S rDNA region, identifying Fonsecaea pedrosoi with 100% homology in all cases. This study identifies F. pedrosoi as the predominant pathogen of CBM in the evaluated samples of Mexican origin and demonstrates the reliability of molecular identification using FFPE samples.

During an 11-month study at two hospital sites, 33 isolates initially classified as the Trichophyton mentagrophytes complex were subjected to whole-genome sequencing. Of these, 24 (72.7%) were identified as T. indotineae and 9 (27.3%) as T. interdigitale, with no T. mentagrophytes detected. Among the 22 patients with available clinical data, 75% exhibited involvement of multiple anatomical sites; although only two patients reported recent travel, 63.6% were migrant workers. Symptom resolution was documented in only four patients, whereas five experienced recurrences. Nearly 80% of T. indotineae isolates displayed terbinafine resistance linked to squalene epoxidase mutations, while no phenotypic azole resistance was observed, consistent with the absence of cyp51 mutations. Single-nucleotide polymorphism (SNP) analysis of both T. indotineae (520-1531 SNPs) and T. interdigitale (1380-115 963 SNPs) revealed no phylogenetic clustering, suggesting independent introductions.

Long-term trends in the antifungal susceptibility of Talaromyces marneffei isolates have not been well characterized. We conducted a 40-year surveillance study analyzing the antifungal susceptibility of 131 T. marneffei isolates collected from the clinical laboratory of the First Affiliated Hospital of Guangxi Medical University between 1984 and 2024. In vitro susceptibilities to conventional antifungal agents, including itraconazole, voriconazole, fluconazole, and amphotericin B, were analyzed using the Clinical and Laboratory Standards Institute broth microdilution method. We also explored the potential influence of host Human Immunodeficiency Virus (HIV) status and fungal mating type (MAT) on susceptibility patterns. The minimum inhibitory concentrations (MICs) for itraconazole, voriconazole, fluconazole, and amphotericin B ranged from 0.015 to 0.06 μg/ml, 0.008 to 0.03 μg/ml, 1 to 8 μg/ml, and 0.25 to 1 μg/ml, respectively. Fluconazole showed a significant decline in susceptibility over time (P < .01), whereas the susceptibilities to the other antifungals remained stable (P > .05). The correlations observed between the MICs of different triazoles (P < .01) suggest potential cross-resistance among triazoles. MAT and HIV infection status did not significantly affect antifungal susceptibility patterns (P > .05). These findings underscore the importance of ongoing antifungal susceptibility surveillance in T. marneffei, considering the changes in fluconazole susceptibility and potential triazole cross-resistance, while other antifungals remain stable.

We evaluated the characteristics and outcomes of ocular candidiasis in patients using buprenorphine intravenously. A retrospective analysis of 35 eyes of people who use drugs diagnosed with presumed ocular candidiasis between 2000 and 2017 was performed. Data on demographics, ocular findings, and microbiological results were extracted from medical records. Logistic regression was performed to identify factors of poor visual prognosis, then multivariate analysis used the variables that were statistically significant in univariate analysis. Most patients (83%) were male, with a mean duration of 7.1 ± 7.3 years from the onset of intravenous use of buprenorphine to diagnosis of ocular candidiasis. The mean best-corrected visual acuity (BCVA in logMAR) at diagnosis was 1.33 ± 0.73, improving significantly to 0.94 ± 0.91 at the last follow-up (P = .019). Diagnostic samples included aqueous humor from all patients and vitrectomy samples from 26 patients (74%), with positivity rates for Candida species culture of 23% and 27%, respectively. Extraocular sites tested positive for Candida in 54% of cases. Although representing 66% of identifications, Candida albicans was not the only identified organism. Treatment involved primarily fluconazole (91%) and intravitreal amphotericin B (69%). Poor visual outcomes correlated with low BCVA and presence of retinal detachment at baseline. Ocular candidiasis occurs in the context of chronic drug use. Diagnostic yield from ocular samples is relatively low, necessitating the investigation of extraocular infection sites or injection equipment. Poor baseline vision and retinal detachment were significant predictors of poor visual prognosis.