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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MDPI AG
2023-11-01
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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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