Medical mycology最新文献

Coccidioidomycosis can cause severe meningitis requiring lifelong treatment. In this study, we sought to better understand the potential effect of pharmacogenomic testing on treatment outcomes of patients with coccidioidal meningitis. Of 13 patients with coccidioidal meningitis who underwent pharmacogenomic testing, 11 had genetic variants of CYP2C19 and CYP3A5 that affect antifungal efficacy. These results led to real-time treatment changes and future antifungal planning. Routine pharmacogenomic testing helps to avoid antifungal treatments that are futile or lead to adverse effects.

Aspergillosis remains a common and life-threatening disease in captive and wild birds all over the world. Diagnosis is currently based on clinical signs or lesions, diagnostic imaging and a variety of biological tests. This systematic review aimed to compare the accuracy of antemortem diagnostic tests for Aspergillus infection in birds. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a search was conducted on PubMed, Scopus, Web of Science, CAB until January 2024. The methodological quality was assessed with QUADAS 2 risk of bias tool. The thirteen studies, selected for the review, included results from a wide variety of birds (mainly Spheniciformes but also Falconiformes, Psittaciformes, and Galliformes) from wildlife rehabilitation centers, zoological parks or veterinary practices. Aspergillus infection was mainly confirmed by fungal culture and/or histopathology. Serum markers included Aspergillus components (galactomannan, ß-D-glucan, mannoproteins and gliotoxin), anti-Aspergillus antibodies, 3-hydroxybutyrate as well as protein electrophoresis and acute phase molecules. Sensitivity and specificity displayed a large amount of variation despite threshold arrangement. Disparities in the number of individuals per study did not allow for reliable comparison. Platelia Ag Assay (Bio-Rad), the most commonly used test in the studies, demonstrated moderate specificity and low sensitivity. Overall, non-specific tests demonstrated more consistent performance, whereas specific tests showed greater variability. Based on current knowledge, none of these tests provide sufficient accuracy to reliably detect Aspergillus infection in birds in clinical practice.

The Candida parapsilosis species complex poses a recognized threat to the nosocomial environment. In the scenario of the global rise of resistant strains to antifungals, geraniol, a terpene isolated from different essential oils, has shown promising antimicrobial activity. We evaluated: (1) the effects of geraniol against the C. parapsilosis species complex, in planktonic and biofilm forms; (2) the strains' susceptibility to clinical antifungals and (3) the geraniol interaction with antifungals. Eighteen isolates were subjected to in vitro susceptibility testing by the broth microdilution protocol, using geraniol, amphotericin B, caspofungin, itraconazole and fluconazole to determine the minimum inhibitory concentration (MIC) and subsequently, we measured the fungicidal activity. Geraniol was tested against biofilms by the measurement of the metabolic activity and biomass. Pharmacological interactions were performed by the checkerboard method. Geraniol's MIC range was between 256 and 512 µg/ml. MIC range for clinical antifungals was ≤ 0.031-4 µg/ml. Geraniol also showed antibiofilm activity with average reductions of metabolic activity (38.33%) and biomass (30.69%), at MIC concentration. Furthermore, geraniol showed synergistic/additive effects with antifungals. Briefly, geraniol inhibits both planktonic cells and biofilms of the C. parapsilosis species complex and besides it improves the efficacy of amphotericin B, caspofungin and fluconazole.

Histoplasmosis is endemic in the central/northeast region of Argentina. It is estimated that the incidence of this mycosis is low in solid organ transplant recipients. This work aims to describe the epidemiology, clinical forms, and evolution of kidney transplant recipients diagnosed with histoplasmosis in Santa Fe city, Argentina. A retrospective study was carried out between 2015 and 2020 on kidney transplant patients with symptoms associated with histoplasmosis in Santa Fe. Histoplasmosis diagnosis was performed through histopathology, recovery of Histoplasma spp., by culture, and/or positive nested Polimerase Chain Reaction (PCR) specific for the Histoplasma Hc100 gene. During the study period, 360 kidney transplantations were performed. Of these patients, 12 were diagnosed with histoplasmosis (3.3%). The patients' median age was 51 years, and 75% were male. Eleven patients (92%) presented the disseminated form of the disease. Thirty-three percent were diagnosed with histoplasmosis in their first year post-transplantation (mostly 6-12 months), while 42% received their diagnosis 3 years after transplantation. Laboratory diagnosis was performed by histopathology, culture, and PCR in four cases (33%), by culture and PCR in three cases (25%), and by PCR alone in three cases (25%). Thus, all 12 patients showed positive nested PCR results. All patients received amphotericin B as initial treatment. A good response was observed in 83% of patients. We found a high incidence of histoplasmosis in kidney transplant recipients (up to 10 times higher than reports from other endemic areas). Diagnosis by histopathology/culture showed 75% sensitivity, while nested PCR showed better sensitivity and diagnostic speed.

A feature of Candida tropicalis is its ability to undergo phenotypic switching that can affect antifungal sensitivity and virulence traits. Here, we investigated the effect of switching on alterations at the cellular structure level of C. tropicalis morphotypes and whether exposure to fluconazole (FLC) in vitro could be associated with these alterations in a morphotype-dependent manner. Candida tropicalis morphotypes included clinical isolate (Parental) and two switch strains (Crepe variant and revertant of Crepe-RC). The minimum inhibitory concentration (MIC50) of fluconazole was determined according to EUCAST. Cell wall porosity, quantification of cell wall components, cell size/complexity, and expression of ERG11 and CDR1 genes in morphotypes pre- and post-exposure to fluconazole were determined. Crepe and RC showed an eightfold higher MIC50 (1 µg/ml) than the Parental (0.125 µg/ml). Exposure to FLC resulted in twofold higher MIC50 for Parental and RC. The Crepe variant exhibited a fourfold higher expression of ERG11, and the RC showed 10-fold higher expression of CDR1 than the clinical isolate. Switch strains showed reduced cell wall porosity compared to Parental, and exposure to FLC resulted in a significant reduction in the porosity of Parental and RC cells. Furthermore, phenotypic switching affected cell wall β-1,3-glucan and chitin contents in a morphotype-dependent manner. Our findings indicate that switching affects cellular structure in C. tropicalis and the occurrence of differential alterations between the clinical isolate and its switched states in response to fluconazole exposure.

Owing to their inherent resistance to different classes of antifungals, early identification of Fusarium spp. is crucial. In this study, 10 clinical isolates were included from patients with invasive fusariosis involving lungs, sinuses, or both. Clinico-radiological data were collected. Samples were processed by standard laboratory procedures. Three gene regions (ITS, TEF1, and RPB2) were amplified by PCR for multilocus sequencing. Fusarium MLST, FUSARIUM-ID, and FUSARIOID-ID databases were used for final identification. Antifungal susceptibility testing was performed by broth microdilution following CLSI M38-A3 and Sensititre™ YeastOne™ YO9 plate. Pulmonary involvement was seen in all patients, and sino-nasal involvement was present in six. Radiologically, consolidations and cavitations were present in eight and six cases, respectively. Halo sign was present in six; reverse halo sign was also found in three of them. Direct microscopy showed septate hyphae that were morphologically different from those found in aspergillosis. Results of the molecular identification were as follows: two Fusarium irregulare, one Fusarium pernambucanum, one Fusarium incarnatum, one Fusarium sp. FIESC 30, two Fusarium keratoplasticum, one Fusarium falciforme, one Fusarium pseudonygamai, and one Fusarium delphinoides. For both Fusarium solani (FSSC) and Fusarium incarnatum-equiseti (FIESC) species complexes, amphotericin B had the lowest minimum inhibitory concentrations (MICs). Importantly, for terbinafine, all FIESC isolates had low MICs, while FSSC isolates had high MICs. In some cases, early identification of Fusarium spp. is possible by means of morphology of hyphae on direct microscopy and findings on radiology. Molecular identification, at least to the species complex level, is crucial for the choice of antifungals.

Species of Malassezia are lipid-dependent yeasts and integral components of the skin microbiome. Most of the currently known species are isolated from mammals. However, the presence and distribution of Malassezia yeasts on the skin of avian species have not been fully understood or elucidated. During a survey on the occurrence of Malassezia species in chickens, 23 Malassezia strains isolated from the healthy skins of chickens may represent two candidate new species of this genus based on the sequence analysis of the internal transcribed spacer (ITS) (including 5.8S rRNA) and the D1/D2 domains of 26S rRNA. The combined ITS and D1/D2 phylogenetic analysis showed that those two candidate new species were closely related to Malassezia slooffiae, and differed from the type of M. slooffiae by 51-62 nucleotides in the ITS region and four nucleotides in the D1/D2 domains, respectively. Based on the phylogenetic analysis and the phenotypic comparison, we propose a new species, named M. gallinae sp. nov., to include the 21 isolated strains.

We evaluated the combined performance of itraconazole and voriconazole Etest® gradient concentration strips for the detection of Aspergillus fumigatus azole resistance associated with cyp51a mutations confirmed by gene sequencing. Among 118 A. fumigatus clinical isolates collected in a French center, 6 (5%) had azole resistance mutations, 5 of which were probably of environmental origin. Using recent method-dependent epidemiological cutoff values as thresholds, the combination's sensitivity and specificity were 100% [95% confidence interval 61-100] and 99% [95-100]. Our results support itraconazole and voriconazole Etest® combined use as a promising self-sufficient method for simple, efficient and reliable cyp51a-related azole-resistant A. fumigatus detection.

(1,3)-β-d-Glucan (BG) assay is a non-invasive test commonly used in the diagnostic of invasive fungal diseases. Given its high sensitivity, it was suggested that a negative BG result is sufficient for excluding the diagnosis of Pneumocystis pneumonia (PCP). However, suboptimal performance has been described in human immunodeficiency virus (HIV)-negative patients, particularly those with haematological malignancies. We aimed to assess the sensitivity of the BG assay for diagnosing PCP in HIV-negative patients based on their underlying PCP risk factors. We conducted a single-center, retrospective study (2009-2021) enrolling HIV-negative patients diagnosed with PCP and who underwent BG testing. Patients colonized with Pneumocystis jirovecii were included as a control group. In all, 55 PCP patients and 61 colonized patients met the inclusion criteria. Patients were further categorized according to the underlying condition that exposes patients to PCP. Median BG concentration was significantly higher in the PCP group than in the colonization group (500 vs. 31 pg/ml; P < 10-4, Mann-Whitney test) and the BG assay demonstrated a sensitivity of 85% and a specificity of 82% for PCP diagnosis. Notably, sensitivity was significantly higher in non-cancer patients (100%) compared to those with solid cancer (72%) and haematologic cancer (79%) (P < .05, Fischer's exact test). These findings strengthen the high performance of BG testing for screening PCP in non-cancer patients, comparable to that observed in HIV-infected individuals. In contrast, they highlight its low reliability in patients with malignancies, emphasizing the importance of considering underlying conditions when interpreting BG results and refining the role of the test in PCP diagnosis.