Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital

The genus <i>Aspergillus</i> harbors human infection-causing pathogens and is involved in the complex one-health challenge of antifungal resistance. Here, a 6-year retrospective study was conducted with <i>Aspergillus</i> spp. isolated from patients with invasive, chronic, an...

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Main Authors: Lívia Maria Maciel da Fonseca, Vanessa Fávaro Braga, Ludmilla Tonani, Patrícia Helena Grizante Barião, Erika Nascimento, Roberto Martinez, Marcia Regina von Zeska Kress
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/9/11/1070
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author Lívia Maria Maciel da Fonseca
Vanessa Fávaro Braga
Ludmilla Tonani
Patrícia Helena Grizante Barião
Erika Nascimento
Roberto Martinez
Marcia Regina von Zeska Kress
author_facet Lívia Maria Maciel da Fonseca
Vanessa Fávaro Braga
Ludmilla Tonani
Patrícia Helena Grizante Barião
Erika Nascimento
Roberto Martinez
Marcia Regina von Zeska Kress
author_sort Lívia Maria Maciel da Fonseca
collection DOAJ
description The genus <i>Aspergillus</i> harbors human infection-causing pathogens and is involved in the complex one-health challenge of antifungal resistance. Here, a 6-year retrospective study was conducted with <i>Aspergillus</i> spp. isolated from patients with invasive, chronic, and clinically suspected aspergillosis in a tertiary teaching hospital. A total of 64 <i>Aspergillus</i> spp. clinical isolates were investigated regarding molecular identification, biofilm, virulence in <i>Galleria mellonella</i>, antifungal susceptibility, and resistance to amphotericin B and azoles. <i>Aspergillus</i> section <i>Fumigati</i> (<i>A. fumigatus sensu stricto</i>, 62.5%) and section <i>Flavi</i> (<i>A. flavus</i>, 20.3%; <i>A. parasiticus</i>, 14%; and <i>A. tamarii</i>, 3.1%) have been identified. <i>Aspergillus</i> section <i>Flavi</i> clinical isolates were more virulent than section <i>Fumigati</i> clinical isolates. Furthermore, scant evidence supports a link between biofilm formation and virulence. The susceptibility of the <i>Aspergillus</i> spp. clinical isolates to itraconazole, posaconazole, voriconazole, and amphotericin B was evaluated. Most <i>Aspergillus</i> spp. clinical isolates (67.2%) had an AMB MIC value equal to or above 2 µg/mL, warning of a higher probability of therapeutic failure in the region under study. In general, the triazoles presented MIC values above the epidemiological cutoff value. The high triazole MIC values of <i>A. fumigatus s.s.</i> clinical isolates were investigated by sequencing the promoter region and <i>cyp51A</i> locus. The Cyp51A amino acid substitutions F46Y, M172V, N248T, N248K, D255E, and E427K were globally detected in 47.5% of <i>A. fumigatus s.s.</i> clinical isolates, and most of them are associated with high triazole MICs. Even so, the findings support voriconazole or itraconazole as the first therapeutic choice for treating <i>Aspergillus</i> infections. This study emphasizes the significance of continued surveillance of <i>Aspergillus</i> spp. infections to help overcome the gap in knowledge of the global fungal burden of infections and antifungal resistance, supporting public health initiatives.
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spelling doaj.art-1a9e0caf192042df8d3d1fea5a9f6ed52023-11-24T14:51:01ZengMDPI AGJournal of Fungi2309-608X2023-11-01911107010.3390/jof9111070Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching HospitalLívia Maria Maciel da Fonseca0Vanessa Fávaro Braga1Ludmilla Tonani2Patrícia Helena Grizante Barião3Erika Nascimento4Roberto Martinez5Marcia Regina von Zeska Kress6Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão, Universidade de Sao Paulo, Ribeirao Preto 14040-903, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão, Universidade de Sao Paulo, Ribeirao Preto 14040-903, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão, Universidade de Sao Paulo, Ribeirao Preto 14040-903, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão, Universidade de Sao Paulo, Ribeirao Preto 14040-903, BrazilDepartamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto 14040-900, BrazilDepartamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto 14040-900, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão, Universidade de Sao Paulo, Ribeirao Preto 14040-903, BrazilThe genus <i>Aspergillus</i> harbors human infection-causing pathogens and is involved in the complex one-health challenge of antifungal resistance. Here, a 6-year retrospective study was conducted with <i>Aspergillus</i> spp. isolated from patients with invasive, chronic, and clinically suspected aspergillosis in a tertiary teaching hospital. A total of 64 <i>Aspergillus</i> spp. clinical isolates were investigated regarding molecular identification, biofilm, virulence in <i>Galleria mellonella</i>, antifungal susceptibility, and resistance to amphotericin B and azoles. <i>Aspergillus</i> section <i>Fumigati</i> (<i>A. fumigatus sensu stricto</i>, 62.5%) and section <i>Flavi</i> (<i>A. flavus</i>, 20.3%; <i>A. parasiticus</i>, 14%; and <i>A. tamarii</i>, 3.1%) have been identified. <i>Aspergillus</i> section <i>Flavi</i> clinical isolates were more virulent than section <i>Fumigati</i> clinical isolates. Furthermore, scant evidence supports a link between biofilm formation and virulence. The susceptibility of the <i>Aspergillus</i> spp. clinical isolates to itraconazole, posaconazole, voriconazole, and amphotericin B was evaluated. Most <i>Aspergillus</i> spp. clinical isolates (67.2%) had an AMB MIC value equal to or above 2 µg/mL, warning of a higher probability of therapeutic failure in the region under study. In general, the triazoles presented MIC values above the epidemiological cutoff value. The high triazole MIC values of <i>A. fumigatus s.s.</i> clinical isolates were investigated by sequencing the promoter region and <i>cyp51A</i> locus. The Cyp51A amino acid substitutions F46Y, M172V, N248T, N248K, D255E, and E427K were globally detected in 47.5% of <i>A. fumigatus s.s.</i> clinical isolates, and most of them are associated with high triazole MICs. Even so, the findings support voriconazole or itraconazole as the first therapeutic choice for treating <i>Aspergillus</i> infections. This study emphasizes the significance of continued surveillance of <i>Aspergillus</i> spp. infections to help overcome the gap in knowledge of the global fungal burden of infections and antifungal resistance, supporting public health initiatives.https://www.mdpi.com/2309-608X/9/11/1070<i>Aspergillus</i> spp.<i>Fumigati</i><i>Flavi</i>Cyp51Aantifungal resistance<i>Galleria mellonella</i>
spellingShingle Lívia Maria Maciel da Fonseca
Vanessa Fávaro Braga
Ludmilla Tonani
Patrícia Helena Grizante Barião
Erika Nascimento
Roberto Martinez
Marcia Regina von Zeska Kress
Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
Journal of Fungi
<i>Aspergillus</i> spp.
<i>Fumigati</i>
<i>Flavi</i>
Cyp51A
antifungal resistance
<i>Galleria mellonella</i>
title Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
title_full Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
title_fullStr Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
title_full_unstemmed Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
title_short Surveillance of Amphotericin B and Azole Resistance in <i>Aspergillus</i> Isolated from Patients in a Tertiary Teaching Hospital
title_sort surveillance of amphotericin b and azole resistance in i aspergillus i isolated from patients in a tertiary teaching hospital
topic <i>Aspergillus</i> spp.
<i>Fumigati</i>
<i>Flavi</i>
Cyp51A
antifungal resistance
<i>Galleria mellonella</i>
url https://www.mdpi.com/2309-608X/9/11/1070
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