162 research outputs found

    Respiratory specimens and the diagnostic accuracy of aspergillus lateral flow assays (LFA-IMMYTM): real life data from a multicenter study

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    Proper diagnosis of invasive aspergillosis is challenging as conventional methods lack sensitivity and are complicated due to time-consuming incubation processes. In order to meet the requirement for early diagnosis the new Aspergillus specific point-of-care test LFA-IMMYTM was evaluated with respect to the ability to accurately detect Aspergillus in broncho-alveolar fluids and sputa and to clarify the potential of cross reactivity with other fungal pathogens

    Farnesol Boosts the Antifungal Effect of Fluconazole and Modulates Resistance in Candida auris through Regulation of the CDR1 and ERG11 Genes

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    Candida auris is considered a serious fungal pathogen frequently exhibiting a high resistance to a wide range of antifungals. In this study, a combination of the quorum-sensing molecule farnesol (FAR) and fluconazole (FLU) was tested on FLU-resistant C. auris isolates (C. auris S and C. auris R) compared to the susceptible C. auris H261. The aim was to assess the possible synergy between FAR and FLU, by reducing the FLU minimal inhibitory concentration, and to determine the mechanism underlying the conjunct effect. The results confirmed a synergic effect between FAR and FLU with a calculated FIC index of 0.75 and 0.4 for C. auris S and C. auris R, respectively. FAR modulates genes involved in azole resistance. When FAR was added to the cells in combination with FLU, a significant decrease in the expression of the CDR1 gene was observed in the resistant C. auris isolates. FAR seems to block the Cdr1 efflux pump triggering a restoration of the intracellular content of FLU. These results were supported by observed increasing accumulation of rhodamine 6G by C. auris cells. Moreover, C. auris treated with FAR showed an ERG11 gene down-regulation. Overall, these results suggest that FAR is an effective modulator of the Cdr1 efflux pump in C. auris and, in combination with FLU, enhances the activity of this azole, which might be a promising strategy to control infections caused by azole-resistant C. auris

    Emergence of terbinafine and azole resistance in dermatophytes: Prevalence in Austria and resistance mechanisms

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    Master thesis - University of Veterinary Medicine Vienna - 2022Introduction and Aim Dermatophytes are primary pathogenic, filamentous fungi infecting hair, skin and nails. Within the past six years, a novel terbinafine-resistant dermatophyte species termed Trichophyton indotineae (Trichophyton mentagrophytes ITS genotype VIII), which was first described in India, has spread to Europe, causing an “epidemic-like scenario” of treatment-resistant dermatophytosis. (Martinez-Rossi et al. 2018, Verma et al. 2021c) However, no studies on the prevalence of this species in Austria have been published so far. Therefore, this master thesis aims to assess the occurrence and potential terbinafine resistance mechanisms in strains identified as part of the Trichophyton mentagrophytes/interdigitale species complex in Austria. Methods 106 dermatophyte strains identified as Trichophyton mentagrophytes (48 strains), Trichophyton interdigitale (48 strains), Trichophyton indotineae (1 strain), or of the Trichophyton mentagrophytes/interdigitale species complex (9 strains) were collected from laboratory test strains and from Austrian clinical isolates over the past 20 years. Antifungal susceptibility testing using the EUCAST microdilution method was performed for the antifungals amorolfine, miconazole, itraconazole, fluconazole, terbinafine, naftifine, griseofulvin and ciclopirox. ERG1 target mutations that cause terbinafine- and possibly naftifine resistance were determined using the DermaGenius® Resistance Multiplex real-time PCR kit (Cat. No. PN-303, PathoNostics, Maastricht, Netherlands) and next-generation sequencing. Results All 106 strains featured low amorolfine, itraconazole, miconazole, fluconazole, griseofulvin, and ciclopirox MIC values. While 104 strains showed low terbinafine and naftifine MIC values, two strains had terbinafine/naftifine MIC values of 0.5/0.5 μg/mL and 4/>8 μg/mL, indicating resistance. The PathoNostics DermaGenius® Resistance Multiplex real-time PCR kit and next-generation sequencing confirmed the presence of ERG1 target mutations. Conclusion Two isolates featured (highly) elevated MIC values to the two allylamines terbinafine and naftifine. As these strains also feature ERG1 mutations, it is possible that they could be cross-resistant to allylamines based on an ERG1 target mutation. Therefore, although the resistance rate is low, antifungal susceptibility testing should be considered in treatment-resistant cases.Masterarbeit - Veterinärmedizinische Universität Wien - 2022Einleitung und Ziel Dermatophyten sind primär pathogene Fadenpilze, welche die Haut, Haare und Nägel infizieren. Innerhalb der letzten sechs Jahre hat sich die neuartige, terbinafinresistente Dermatophytenspezies Trichophyton indotineae (Trichophyton mentagrophytes ITS-Genotyp VIII), welche zuerst in Indien beschrieben wurde, bis nach Europa ausgebreitet und verursacht nun eine epidemieartige Welle an therapieresistenten Dermatomykosen. (Martinez-Rossi et al. 2018, Verma et al. 2021c) Da bisher noch keine Prävalenzstudien über resistente Dermatophyten in Österreich durchgeführt wurden, ist das Ziel dieser Masterarbeit, das Vorkommen sowie mögliche Resistenzmutationen im Trichophyton mentagrophytes/interdigitale-Spezieskomplex in Österreich festzustellen. Methoden 106 Dermatophytenstämme, welche zuvor als Trichophyton mentagrophytes (48 Stämme), Trichophyton interdigitale (48 Stämme), Trichophyton indotineae (1 Stamm), oder als Teil des Trichophyton mentagrophytes/interdigitale-Spezieskomplex (9 Stämme) identifiziert wurden, wurden aus Labor-Teststämmen oder aus österreichischen Patientenisolaten innerhalb der letzten 20 Jahre gesammelt. Antimykotika-Resistenztestungen wurden mithilfe der EUCAST-Mikrodilutionsmethode für die Antimykotika Amorolfin, Miconazol, Itraconazol, Fluconazol, Terbinafin, Naftifin und Ciclopirox durchgeführt. ERG1-Targetmutationen, welche Terbinafin- und möglicherweise auch Naftifinresistenzen hervorrufen, wurden mithilfe des DermaGenius® Resistance Multiplex real-time PCR kit (Cat. No. PN-303, PathoNostics, Maastricht, Niederlande) und Next-Generation Sequencing ermittelt. Resultate Alle 106 Dermatophytenstämme wiesen niedrige Amorolfin-, Itraconazol-, Miconazol-, Fluconazol-, Griseofulvin-, und Ciclopirox-MHK-Werte auf. 104 Stämme hatten niedrige Terbinafin- und Naftifin-MHK-Werte, während zwei Stämme erhöhte Terbinafin-/Naftifin-MHK-Werte von 0.5/0.5 μg/mL und 4/>8 μg/mL hatten, welche für eine Resistenz sprechen könnten. Die Präsenz von ERG1-Targetmutationen wurde mithilfe vom PathoNostics DermaGenius® Resistance Multiplex real-time PCR kit und von Next-Generation Sequencing nachgewiesen. Konklusion Zwei Isolate, welche (stark) erhöhte MHK-Werte gegen die Allylamine Terbinafin und Naftifin aufwiesen, weisen ERG1-Targetmutationen auf. Da erhöhte Terbinafin- und Naftifin-MHK-Werte stets gemeinsam auftreten, besteht die Möglichkeit, dass ERG1-Targetmutationen Kreuzresistenzen gegen alle Antimykotika der Klasse der Allylamine hervorrufen. Daher sollte die Antimykotika-Resistenztestung in behandlungsresistenten Fällen trotz der niedrigen Resistenzrate in dieser Studie in Erwägung gezogen werden.Master thesis - University of Veterinary Medicine Vienna - 2022Introduction and Aim Dermatophytes are primary pathogenic, filamentous fungi infecting hair, skin and nails. Within the past six years, a novel terbinafine-resistant dermatophyte species termed Trichophyton indotineae (Trichophyton mentagrophytes ITS genotype VIII), which was first described in India, has spread to Europe, causing an “epidemic-like scenario” of treatment-resistant dermatophytosis. (Martinez-Rossi et al. 2018, Verma et al. 2021c) However, no studies on the prevalence of this species in Austria have been published so far. Therefore, this master thesis aims to assess the occurrence and potential terbinafine resistance mechanisms in strains identified as part of the Trichophyton mentagrophytes/interdigitale species complex in Austria. Methods 106 dermatophyte strains identified as Trichophyton mentagrophytes (48 strains), Trichophyton interdigitale (48 strains), Trichophyton indotineae (1 strain), or of the Trichophyton mentagrophytes/interdigitale species complex (9 strains) were collected from laboratory test strains and from Austrian clinical isolates over the past 20 years. Antifungal susceptibility testing using the EUCAST microdilution method was performed for the antifungals amorolfine, miconazole, itraconazole, fluconazole, terbinafine, naftifine, griseofulvin and ciclopirox. ERG1 target mutations that cause terbinafine- and possibly naftifine resistance were determined using the DermaGenius® Resistance Multiplex real-time PCR kit (Cat. No. PN-303, PathoNostics, Maastricht, Netherlands) and next-generation sequencing. Results All 106 strains featured low amorolfine, itraconazole, miconazole, fluconazole, griseofulvin, and ciclopirox MIC values. While 104 strains showed low terbinafine and naftifine MIC values, two strains had terbinafine/naftifine MIC values of 0.5/0.5 μg/mL and 4/>8 μg/mL, indicating resistance. The PathoNostics DermaGenius® Resistance Multiplex real-time PCR kit and next-generation sequencing confirmed the presence of ERG1 target mutations. Conclusion Two isolates featured (highly) elevated MIC values to the two allylamines terbinafine and naftifine. As these strains also feature ERG1 mutations, it is possible that they could be cross-resistant to allylamines based on an ERG1 target mutation. Therefore, although the resistance rate is low, antifungal susceptibility testing should be considered in treatment-resistant cases

    Emerging Fungi and Diagnosis of Fungal Infections: Current Knowledge and New Developments

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    I would like to thank all the authors contributing to this Special Issue [...

    Culture-Based Techniques

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    What Is the Target? Clinical Mycology and Diagnostics

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    Wiener klinisches Magazin / Moderne Pilzdiagnostik : Fluch oder Segen?

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    Die Diagnose von invasiven Pilzinfektionen ist nach wie vor schwierig. Sie setzt sich aus mehreren Schritten zusammen und basiert auf der gemeinsamen Bewertung von klinischen Symptomen, radiologischen Befunden, Ergebnissen der histologischen Untersuchung sowie klinisch-chemischen und mikrobiologischen Parametern. Erst in der Zusammenschau und gemeinsamen Beurteilung all dieser Befunde ist es möglich, die Diagnose zu stellen. Neue Entwicklungen vor allem auf dem Gebiet der molekularbiologischen Techniken wie auch der Einsatz von Biomarkern bei immunologisch-serologischen Untersuchungen haben wesentliche Verbesserungen im Sinne einer frühzeitigen und raschen Diagnostik gebracht. Trotzdem ist es nach wie vor notwendig, unterschiedliche Testverfahren zu kombinieren, um zu einer verlässlichen Diagnose zu kommen.The diagnosis of invasive fungal infections remains difficult. It consists of several steps and is based on the joint evaluation of clinical symptoms, radiological findings, histological examination results, clinicochemical and microbiological parameters. A diagnosis can first be made by a synopsis and total assessment of all these findings. New developments, especially in the field of molecular biological techniques and the use of biomarkers in immunological and serological investigations have resulted in significant improvements in terms of early and rapid diagnosis. Nevertheless, the combination of various test procedures is mandatory to enable earlier and reliable diagnosis of systemic fungal infections

    species

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    Emerg Infect Dis

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    The emerging pathogen Candida auris is isolated mostly from hospitalized patients and often shows multidrug resistance. We report on the isolation of this yeast in Austria from an outpatient's auditory canal. The isolate showed good susceptibility against antifungals except for echinocandins; the patient was treated successfully with topical administration of nystatin

    Corrigendum: Azole-resistance in aspergillus terreusand related species: An emerging problem or a rare phenomenon? (Frontiers in Microbiology (2018) 9 (516) DOI: 10.3389/fmicb.2018.00516)

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    Raquel Sabino was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2019 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Lo Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Sabino, Lass-Flörl and Lackner
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