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      Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen

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          Abstract

          Objectives: This review aimed to better depict the clinical features and address the issue of therapeutic management of Trichosporon deep-seated infections.

          Methods: We comprehensively reviewed the cases of invasive Trichosporon infection reported in the literature from 1994 (date of taxonomic modification) to 2015. Data from antifungal susceptibility testing (AST) studies were also analyzed.

          Results: Two hundred and three cases were retained and split into four groups: homeopathy ( n = 79), other immunodeficiency conditions ( n = 41), miscellaneous ( n = 58) and newborns ( n = 25). Trichosporon asahii was the main causative species (46.7%) and may exhibit cross-resistance to different antifungal classes. The unfavorable outcome rate was at 44.3%. By multivariate analysis, breakthrough infection (OR 2.45) was associated with unfavorable outcome, whilst the use of an azole-based therapy improved the prognosis (OR 0.16). Voriconazole-based treatment was associated with favorable outcome in hematological patients (73.6 vs. 41.8%; p = 0.016). Compiled data from AST demonstrated that (i) T. asahii exhibits the highest MICs to amphotericin B and (ii) voriconazole has the best in vitro efficacy against clinical isolates of Trichosporon spp.

          Conclusions: Trichosporon infection is not only restricted to hematological patients. Analysis of compiled data from AST and clinical outcome support the use of voriconazole as first line therapy.

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          Current knowledge of Trichosporon spp. and Trichosporonosis.

          Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.
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            ESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections.

            The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive treatment was reviewed. In addition, remarks about antifungal susceptibility testing were made. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
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              Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.

              Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                17 October 2016
                2016
                : 7
                : 1629
                Affiliations
                [1] 1Central Laboratory Division-LIM03, Faculdade de Medicina da Universidade de São Paulo São Paulo, Brazil
                [2] 2Laboratory of Medical Mycology-LIM53, Instituto de Medicina Tropical da Universidade de São Paulo São Paulo, Brazil
                [3] 3Service de Parasitologie-Mycologie-AP-HP, Hôpital St Antoine Paris, France
                [4] 4Institut National de la Santé et de la Recherche Médicale UMR 1135, Centre National de la Recherche Scientifique ERL 8255, Sorbonne Universités, University Pierre and Marie Curie (UPMC) Paris, France
                [5] 5Centre d'Immunologie et des Maladies Infectieuses, Bd de l'hôpital Paris, France
                Author notes

                Edited by: Frederic Lamoth, Lausanne University Hospital, Switzerland

                Reviewed by: Oscar Zaragoza, Instituto de Salud Carlos III, Spain; Anuradha Chowdhary, University of Delhi, India

                *Correspondence: João Nobrega de Almeida Júnior jnaj99@ 123456gmail.com

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.01629
                5065970
                27799926
                58264e17-e257-4c5a-9290-b29769173cd3
                Copyright © 2016 de Almeida Júnior and Hennequin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 June 2016
                : 29 September 2016
                Page count
                Figures: 1, Tables: 8, Equations: 0, References: 185, Pages: 18, Words: 14167
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 2011/08911-0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                trichosporon species,invasive infection,risk factors,prognosis,diagnosis,treatment,antifungal resistance

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