Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/55799 http://dx.doi.org/10.3389/fmicb.2018.00516 |
Resumo: | Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods : A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results : The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions : Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole. |
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Zoran, TamaraSartori, BettinaSappl, LauraAigner, MariaSanchez-Reus, FerranRezusta, AntonioChowdhary, AnuradhaTaj-Aldeen, Saad J.Arendrup, Maiken C.Oliveri, SalvatoreKontoyiannis, Dimitrios P.Alastruey-Izquierdo, AnaLagrou, KatrienLo Cascio, GiulianaMeis, Jacques F.Buzina, WalterFarina, ClaudioDrogari-Apiranthitou, MirandaGrancini, AnnaTortorano, Anna M.Willinger, BirgitHamprecht, AxelJohnson, ElizabethKlingspor, LenaArsic-Arsenijevic, ValentinaCornely, Oliver A.Meletiadis, JosephPrammer, WolfgangTullio, VivianVehreschild, Jorg-JanneTrovato, LauraLewis, Russell E.Segal, EstherRath, Peter-MichaelHamal, PetrRodriguez-Iglesias, ManuelRoilides, EmmanuelArikan-Akdagli, SevtapChakrabarti, ArunalokeColombo, Arnaldo Lopes [UNIFESP]Fernandez, Mariana S.Teresa Martin-Gomez, M.Badali, HamidPetrikkos, GeorgiosKlimko, NikolaiHeimann, Sebastian M.Uzun, OmrumRoudbary, Maryamde la Fuente, SoniaHoubraken, JosRisslegger, BrigitteLass-Floerl, CorneliaLackner, Michaela2020-07-20T16:31:13Z2020-07-20T16:31:13Z2018Frontiers In Microbiology. Lausanne, v. 9, 2018.1664-302Xhttps://repositorio.unifesp.br/handle/11600/55799http://dx.doi.org/10.3389/fmicb.2018.00516WOS000428531200001.pdf10.3389/fmicb.2018.00516WOS:000428531200001Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods : A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results : The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions : Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.ECMMISHAMEFISGAstellasMSDPfizerChristian Doppler Laboratory for invasive fungal infectionsMed Univ Innsbruck, Div Hyg & Med Microbiol, Innsbruck, AustriaHosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona, SpainUniv Zaragoza, Hosp Univ Miguel Servet, IIS Aragon, Microbiol, Zaragoza, SpainUniv Delhi, Vallabhbhai Patel Chest Inst, Dept Med Mycol, New Delhi, IndiaHamad Med Corp, Dept Lab Med & Pathol, Microbiol Div, Doha, QatarUniv Copenhagen, Rigshosp, Dept Clin Microbiol, Unit Mycol,Statens Serum Inst, Copenhagen, DenmarkUniv Catania, Dept Biomed & Biotechnol Sci, Catania, ItalyUniv Texas MD Anderson Canc Ctr, Houston, TX USAInst Salud Carlos III, Natl Ctr Microbiol, Madrid, SpainKatholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, BelgiumUniv Integrata, Azienda Osped, Dipartimento Patol Diagnost, Unita Operat Complessa Microbiol & Virol, Verona, ItalyCanisius Wilhelmina Hosp, Dept Med Microbiol & Infect Dis, Nijmegen, NetherlandsMed Univ Graz, Inst Hyg Microbiol & Environm Med, Graz, AustriaASST Papa Giovanni XXIII, Microbiol Inst, Bergamo, ItalyUniv Athens, ATTIKON Univ Hosp, Dept Internal Med 4, Infect Dis Res Lab, Athens, GreeceCa Granda Osped Maggiore Policlin, IRCCS Fdn, Lab Cent Analisi Chim Clin & Microbiol, Milan, ItalyUniv Milan, Dept Biomed Sci Hlth, Milan, ItalyMed Univ Vienna, Dept Lab Med, Div Clin Microbiol, Vienna, AustriaUniv Cologne, Inst Med Microbiol Immunol & Hyg, Cologne, GermanyPubl Hlth England, Mycol Reference Lab, Bristol, Avon, EnglandKarolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Stockholm, SwedenUniv Belgrade, Inst Microbiol & Immunol, Fac Med, Natl Reference Med Mycol Lab, Belgrade, SerbiaUniv Cologne, German Ctr Infect Res, Ctr Integrated Oncol CIO Koln Bonn,Clin Trials Ct, Dept Internal Med,Cologne Excellence Cluster Cell, Cologne, GermanyATTIKON Univ, Hosp Athens, Natl Kapodistrian Univ Athens, Clin Microbiol Lab, Athens, GreeceKlinikum Wels Grieskirchen, Dept Hyg & Med Microbiol, Wels, AustriaDiv Microbiol, Dept Publ Hlth & Pediat, Turin, ItalyUniv Hosp Cologne, Dept Internal Med, Cologne, GermanyPartner Site Bonn Cologne, German Ctr Infect Res, Cologne, GermanyBiometec Univ Catania, AOU Policlin Vittorio Emanuele Catania, Catania, ItalyUniv Bologna, S Orsola Malpighi, Dept Med & Surg Sci, Infect Dis Unit, Bologna, ItalyTel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, Tel Aviv, IsraelUniv Duisburg Essen, Univ Hosp Essen, Inst Med Microbiol, Essen, GermanyPalacky Univ Olomouc, Fac Med & Dent, Dept Microbiol, Olomouc, Czech RepublicUniv Hosp Olomouc, Olomouc, Czech RepublicUniv Cadiz, Puerta Mar Univ Hosp, Clin Microbiol, Cadiz, SpainHippokrateion Hosp, Aristotle Univ Sch Hlth Sci, Fac Med, Infect Dis Unit,Dept Pediat 3, Thessaloniki, GreeceHacettepe Univ Med Sch, Dept Med Microbiol, Ankara, TurkeyPostgrad Inst Med Educ & Res, Dept Medial Microbiol, Div Mycol, Chandigarh, IndiaUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilUniv Nacl Nordeste, CONICET, Inst Medicina Reg, Dept Micol, Resistencia, ArgentinaVall Hebron Univ Hosp, Dept Microbiol, Div Clin Mycol, Barcelona, SpainMazandaran Univ Med Sci, Dept Med Mycol & Parasitol, Invas Fungi Res Ctr, Sari, IranEuropean Univ Cyprus, Sch Med, Nicosia, CyprusNorth Western State Med Univ, Dept Clin Mycol Allergy & Immunol, St Petersburg, RussiaUniv Hosp Cologne, Dept Internal Med, Cologne, GermanyHacettepe Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Ankara, TurkeyIran Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Tehran, IranHosp Ernest Lluch Martin, Dept Dermatol, Zaragoza, SpainWesterdijk Fungal Biodivers Inst, Dept Appl & Ind Mycol, Utrecht, NetherlandsUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilWeb of Science-engFrontiers Media SaFrontiers In Microbiologycryptic speciesAspergillus section Terreisusceptibility profilesazolesCyp51A alterationsAzole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLausannev. 9info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000428531200001.pdfapplication/pdf1349672${dspace.ui.url}/bitstream/11600/55799/1/WOS000428531200001.pdf4afdc12c349dcc94fc81a79543b5e19bMD51open accessTEXTWOS000428531200001.pdf.txtWOS000428531200001.pdf.txtExtracted texttext/plain43226${dspace.ui.url}/bitstream/11600/55799/2/WOS000428531200001.pdf.txt929d9b22ba22f0785b1b13aa65768442MD52open accessTHUMBNAILWOS000428531200001.pdf.jpgWOS000428531200001.pdf.jpgIM Thumbnailimage/jpeg7227${dspace.ui.url}/bitstream/11600/55799/4/WOS000428531200001.pdf.jpg20e18cab9d8f7821925d4ea4346c984dMD54open access11600/557992022-08-01 02:17:01.989open 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dc.title.en.fl_str_mv |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
title |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
spellingShingle |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? Zoran, Tamara cryptic species Aspergillus section Terrei susceptibility profiles azoles Cyp51A alterations |
title_short |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
title_full |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
title_fullStr |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
title_full_unstemmed |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
title_sort |
Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? |
author |
Zoran, Tamara |
author_facet |
Zoran, Tamara Sartori, Bettina Sappl, Laura Aigner, Maria Sanchez-Reus, Ferran Rezusta, Antonio Chowdhary, Anuradha Taj-Aldeen, Saad J. Arendrup, Maiken C. Oliveri, Salvatore Kontoyiannis, Dimitrios P. Alastruey-Izquierdo, Ana Lagrou, Katrien Lo Cascio, Giuliana Meis, Jacques F. Buzina, Walter Farina, Claudio Drogari-Apiranthitou, Miranda Grancini, Anna Tortorano, Anna M. Willinger, Birgit Hamprecht, Axel Johnson, Elizabeth Klingspor, Lena Arsic-Arsenijevic, Valentina Cornely, Oliver A. Meletiadis, Joseph Prammer, Wolfgang Tullio, Vivian Vehreschild, Jorg-Janne Trovato, Laura Lewis, Russell E. Segal, Esther Rath, Peter-Michael Hamal, Petr Rodriguez-Iglesias, Manuel Roilides, Emmanuel Arikan-Akdagli, Sevtap Chakrabarti, Arunaloke Colombo, Arnaldo Lopes [UNIFESP] Fernandez, Mariana S. Teresa Martin-Gomez, M. Badali, Hamid Petrikkos, Georgios Klimko, Nikolai Heimann, Sebastian M. Uzun, Omrum Roudbary, Maryam de la Fuente, Sonia Houbraken, Jos Risslegger, Brigitte Lass-Floerl, Cornelia Lackner, Michaela |
author_role |
author |
author2 |
Sartori, Bettina Sappl, Laura Aigner, Maria Sanchez-Reus, Ferran Rezusta, Antonio Chowdhary, Anuradha Taj-Aldeen, Saad J. Arendrup, Maiken C. Oliveri, Salvatore Kontoyiannis, Dimitrios P. Alastruey-Izquierdo, Ana Lagrou, Katrien Lo Cascio, Giuliana Meis, Jacques F. Buzina, Walter Farina, Claudio Drogari-Apiranthitou, Miranda Grancini, Anna Tortorano, Anna M. Willinger, Birgit Hamprecht, Axel Johnson, Elizabeth Klingspor, Lena Arsic-Arsenijevic, Valentina Cornely, Oliver A. Meletiadis, Joseph Prammer, Wolfgang Tullio, Vivian Vehreschild, Jorg-Janne Trovato, Laura Lewis, Russell E. Segal, Esther Rath, Peter-Michael Hamal, Petr Rodriguez-Iglesias, Manuel Roilides, Emmanuel Arikan-Akdagli, Sevtap Chakrabarti, Arunaloke Colombo, Arnaldo Lopes [UNIFESP] Fernandez, Mariana S. Teresa Martin-Gomez, M. Badali, Hamid Petrikkos, Georgios Klimko, Nikolai Heimann, Sebastian M. Uzun, Omrum Roudbary, Maryam de la Fuente, Sonia Houbraken, Jos Risslegger, Brigitte Lass-Floerl, Cornelia Lackner, Michaela |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Zoran, Tamara Sartori, Bettina Sappl, Laura Aigner, Maria Sanchez-Reus, Ferran Rezusta, Antonio Chowdhary, Anuradha Taj-Aldeen, Saad J. Arendrup, Maiken C. Oliveri, Salvatore Kontoyiannis, Dimitrios P. Alastruey-Izquierdo, Ana Lagrou, Katrien Lo Cascio, Giuliana Meis, Jacques F. Buzina, Walter Farina, Claudio Drogari-Apiranthitou, Miranda Grancini, Anna Tortorano, Anna M. Willinger, Birgit Hamprecht, Axel Johnson, Elizabeth Klingspor, Lena Arsic-Arsenijevic, Valentina Cornely, Oliver A. Meletiadis, Joseph Prammer, Wolfgang Tullio, Vivian Vehreschild, Jorg-Janne Trovato, Laura Lewis, Russell E. Segal, Esther Rath, Peter-Michael Hamal, Petr Rodriguez-Iglesias, Manuel Roilides, Emmanuel Arikan-Akdagli, Sevtap Chakrabarti, Arunaloke Colombo, Arnaldo Lopes [UNIFESP] Fernandez, Mariana S. Teresa Martin-Gomez, M. Badali, Hamid Petrikkos, Georgios Klimko, Nikolai Heimann, Sebastian M. Uzun, Omrum Roudbary, Maryam de la Fuente, Sonia Houbraken, Jos Risslegger, Brigitte Lass-Floerl, Cornelia Lackner, Michaela |
dc.subject.eng.fl_str_mv |
cryptic species Aspergillus section Terrei susceptibility profiles azoles Cyp51A alterations |
topic |
cryptic species Aspergillus section Terrei susceptibility profiles azoles Cyp51A alterations |
description |
Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods : A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results : The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions : Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole. |
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2018 |
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2018 |
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2020-07-20T16:31:13Z |
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2020-07-20T16:31:13Z |
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Frontiers In Microbiology. Lausanne, v. 9, 2018. |
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https://repositorio.unifesp.br/handle/11600/55799 http://dx.doi.org/10.3389/fmicb.2018.00516 |
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1664-302X |
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WOS000428531200001.pdf |
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10.3389/fmicb.2018.00516 |
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Frontiers In Microbiology. Lausanne, v. 9, 2018. 1664-302X WOS000428531200001.pdf 10.3389/fmicb.2018.00516 WOS:000428531200001 |
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https://repositorio.unifesp.br/handle/11600/55799 http://dx.doi.org/10.3389/fmicb.2018.00516 |
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