Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário

Detalhes bibliográficos
Autor(a) principal: Sousa, Romulo Pereira de Moura
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/19093
Resumo: Systemic candidiasis, also known as invasive candidiasis, is an opportunistic fungal infection caused by yeasts of the genus Candida. The invasive form is the most serious manifestation due to its spread to other organs, promoting prolonged hospitalization and high morbidity and mortality rates. The treatment for this severe infection still has a small therapeutic arsenal, which is summarized in three classes: triazolic agents, the echinocandins and the polyenes. Although the first-line drugs (triazolic agents and echinocandins) are effective, some Candida species are naturally resistant and others develop acquired resistance, the latter having been occurring increasingly and causing great concern due to the appearance of fungal multiresistance. Faced with this worrying picture, the search for new pharmacotherapeutic alternatives has been constant, and one of the sources of potentially active substances are the synthetic compounds. Based on the pharmacological potential of the synthetic substances, this study investigated the in vitro antifungal activity of the synthetic compound 2-bromo-N-phenylacetamide by determining the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (CFM) of Candida isolates from patients with invasive candidiasis assisted at the Lauro Wanderley University Hospital, João Pessoa-PB, in the year 2017. In addition, it identified the etiological agents and their sensitivity profiles through the Candifast® Kit, compared to the identification performed through laboratory methods, and finally assessed the association of the test substance with fluconazole. Thus, the present study revealed that 25 cases of invasive candidiasis were diagnosed, of which 56% were from patients in the intensive care unit of the hospital, and C. albicans was the most common etiological agent (52%), and that of the 15 clinical isolates chosen to follow up on this research, 47% were resistant to fluconazole, of which six (06) isolates of C. albicans and one (01) of the C. parapsilosis complex. In the antifungal activity assays, the test substance had CIM50 of 8 μg/mL for C. albicans and 16 μg/mL for C. parapsilosis complex, and CFM50 of 16 μg/mL and 32 μg/mL, respectively. The association between 2-bromo-N-phenylacetamide and fluconazole did not show synergism or antagonism, being characterized as indifferent. Therefore, the present study revealed that in the year 2017, the majority of cases of invasive candidiasis came from inpatients in the intensive care unit of the university hospital, with C. albicans as the most common etiological agent and fluconazole as the only Candifast® kit which showed resistance (47%). In addition, this was the first study with the synthetic substance 2-bromo-N-phenylacetamide, which showed a strong fungicidal activity against clinical isolates of C. albicans and C. parapsilosis complex, however, this substance was indifferent when associated with fluconazole.
id UFPB_a3d96c41381d7945639b024194ee3ef0
oai_identifier_str oai:repositorio.ufpb.br:123456789/19093
network_acronym_str UFPB
network_name_str Biblioteca Digital de Teses e Dissertações da UFPB
repository_id_str
spelling Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitárioCandida albicansComplexo Candida parapsilosisCandidíase invasivaCandida parapsilosis complexInvasive candidiasisCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIASystemic candidiasis, also known as invasive candidiasis, is an opportunistic fungal infection caused by yeasts of the genus Candida. The invasive form is the most serious manifestation due to its spread to other organs, promoting prolonged hospitalization and high morbidity and mortality rates. The treatment for this severe infection still has a small therapeutic arsenal, which is summarized in three classes: triazolic agents, the echinocandins and the polyenes. Although the first-line drugs (triazolic agents and echinocandins) are effective, some Candida species are naturally resistant and others develop acquired resistance, the latter having been occurring increasingly and causing great concern due to the appearance of fungal multiresistance. Faced with this worrying picture, the search for new pharmacotherapeutic alternatives has been constant, and one of the sources of potentially active substances are the synthetic compounds. Based on the pharmacological potential of the synthetic substances, this study investigated the in vitro antifungal activity of the synthetic compound 2-bromo-N-phenylacetamide by determining the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (CFM) of Candida isolates from patients with invasive candidiasis assisted at the Lauro Wanderley University Hospital, João Pessoa-PB, in the year 2017. In addition, it identified the etiological agents and their sensitivity profiles through the Candifast® Kit, compared to the identification performed through laboratory methods, and finally assessed the association of the test substance with fluconazole. Thus, the present study revealed that 25 cases of invasive candidiasis were diagnosed, of which 56% were from patients in the intensive care unit of the hospital, and C. albicans was the most common etiological agent (52%), and that of the 15 clinical isolates chosen to follow up on this research, 47% were resistant to fluconazole, of which six (06) isolates of C. albicans and one (01) of the C. parapsilosis complex. In the antifungal activity assays, the test substance had CIM50 of 8 μg/mL for C. albicans and 16 μg/mL for C. parapsilosis complex, and CFM50 of 16 μg/mL and 32 μg/mL, respectively. The association between 2-bromo-N-phenylacetamide and fluconazole did not show synergism or antagonism, being characterized as indifferent. Therefore, the present study revealed that in the year 2017, the majority of cases of invasive candidiasis came from inpatients in the intensive care unit of the university hospital, with C. albicans as the most common etiological agent and fluconazole as the only Candifast® kit which showed resistance (47%). In addition, this was the first study with the synthetic substance 2-bromo-N-phenylacetamide, which showed a strong fungicidal activity against clinical isolates of C. albicans and C. parapsilosis complex, however, this substance was indifferent when associated with fluconazole.NenhumaA candidíase sistêmica, também conhecida como candidíase invasiva, é uma infecção fúngica oportunista provocada por leveduras do gênero Candida. A forma invasiva é a manifestação mais grave em decorrência de sua disseminação para outros órgãos, promovendo hospitalização prolongada e altas taxas de morbimortalidade. O tratamento para essa infecção grave ainda dispõe de um pequeno arsenal terapêutico, o qual se resume em três classes: agentes triazólicos, as equinocandinas e os polienos. Embora os fármacos de primeira linha (agentes triazólicos e as equinocandinas) sejam eficazes, algumas espécies de Candida são naturalmente resistentes e outras desenvolvem resistência adquirida, esta última vem ocorrendo de forma crescente e causando uma grande preocupação devido ao surgimento da multirresistência fúngica. Diante desse quadro preocupante, a busca por novas alternativas farmacoterapêuticas tem sido constante, e uma das fontes de substâncias potencialmente ativas são os compostos sintéticos. Destarte, com base no potencial farmacológico das substâncias sintéticas, este estudo investigou a atividade antifúngica in vitro do composto sintético 2-bromo-N-fenilacetamida através da determinação da Concentração Inibitória Mínima (CIM) e Concentração Fungicida Mínima (CFM), frente às espécies de Candida isoladas de pacientes com candidíase invasiva assistidos no Hospital Universitário Lauro Wanderley, João Pessoa-PB, no ano de 2017. Ademais, identificou os agentes etiológicos e seus perfis de sensibilidade através do Kit comercial Candifast®, comparou com a identificação realizada através de métodos laboratoriais, e por fim, avaliou a associação da substância teste com o fluconazol. Assim sendo, a presente pesquisa revelou que foram diagnosticados 25 casos de candidíase invasiva, dos quais, 56% foram provenientes de pacientes internos nas unidades de terapia intensiva do citado hospital, tendo a espécie C. albicans como agente etiológico mais comum (52%), e que, dos 15 isolados clínicos escolhidos para dar seguimento a esta pesquisa, 47% foram resistentes ao fluconazol, dos quais, seis (06) isolados de C. albicans e um (01) do complexo C. parapsilosis. Nos ensaios de atividade antifúngica, a substância teste apresentou CIM50 de 8 μg/mL para C. albicans e 16 μg/mL para o complexo C. parapsilosis, e CFM50 de 16 μg/mL e 32 μg/mL, respectivamente. A associação entre a 2-bromo-N-fenilacetamida com o fluconazol não apresentou sinergismo ou antagonismo, sendo caracterizada como indiferente. Portanto, o presente estudo revelou que no ano de 2017, a maioria dos casos de candidíase invasiva foi proveniente de pacientes internos no centro de terapia intensiva do referido hospital universitário, tendo a espécie C. albicans como agente etiológico mais comum e o fluconazol como único fármaco do kit Candifast® que apresentou resistência (47%). Além disso, este foi o primeiro estudo com a substância sintética 2-bromo-N-fenilacetamida, a qual mostrou uma forte atividade fungicida contra isolados clínicos de C. albicans e do complexo C. parapsilosis, no entanto, tal substância se mostrou indiferente quando associada com o fluconazol.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBLima, Edeltrudes de Oliveirahttp://lattes.cnpq.br/9406572870167006Sousa, Romulo Pereira de Moura2021-01-02T21:51:35Z2019-08-082021-01-02T21:51:35Z2019-06-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/19093porhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2021-08-19T13:46:02Zoai:repositorio.ufpb.br:123456789/19093Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2021-08-19T13:46:02Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
title Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
spellingShingle Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
Sousa, Romulo Pereira de Moura
Candida albicans
Complexo Candida parapsilosis
Candidíase invasiva
Candida parapsilosis complex
Invasive candidiasis
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
title_full Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
title_fullStr Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
title_full_unstemmed Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
title_sort Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
author Sousa, Romulo Pereira de Moura
author_facet Sousa, Romulo Pereira de Moura
author_role author
dc.contributor.none.fl_str_mv Lima, Edeltrudes de Oliveira
http://lattes.cnpq.br/9406572870167006
dc.contributor.author.fl_str_mv Sousa, Romulo Pereira de Moura
dc.subject.por.fl_str_mv Candida albicans
Complexo Candida parapsilosis
Candidíase invasiva
Candida parapsilosis complex
Invasive candidiasis
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Candida albicans
Complexo Candida parapsilosis
Candidíase invasiva
Candida parapsilosis complex
Invasive candidiasis
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Systemic candidiasis, also known as invasive candidiasis, is an opportunistic fungal infection caused by yeasts of the genus Candida. The invasive form is the most serious manifestation due to its spread to other organs, promoting prolonged hospitalization and high morbidity and mortality rates. The treatment for this severe infection still has a small therapeutic arsenal, which is summarized in three classes: triazolic agents, the echinocandins and the polyenes. Although the first-line drugs (triazolic agents and echinocandins) are effective, some Candida species are naturally resistant and others develop acquired resistance, the latter having been occurring increasingly and causing great concern due to the appearance of fungal multiresistance. Faced with this worrying picture, the search for new pharmacotherapeutic alternatives has been constant, and one of the sources of potentially active substances are the synthetic compounds. Based on the pharmacological potential of the synthetic substances, this study investigated the in vitro antifungal activity of the synthetic compound 2-bromo-N-phenylacetamide by determining the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (CFM) of Candida isolates from patients with invasive candidiasis assisted at the Lauro Wanderley University Hospital, João Pessoa-PB, in the year 2017. In addition, it identified the etiological agents and their sensitivity profiles through the Candifast® Kit, compared to the identification performed through laboratory methods, and finally assessed the association of the test substance with fluconazole. Thus, the present study revealed that 25 cases of invasive candidiasis were diagnosed, of which 56% were from patients in the intensive care unit of the hospital, and C. albicans was the most common etiological agent (52%), and that of the 15 clinical isolates chosen to follow up on this research, 47% were resistant to fluconazole, of which six (06) isolates of C. albicans and one (01) of the C. parapsilosis complex. In the antifungal activity assays, the test substance had CIM50 of 8 μg/mL for C. albicans and 16 μg/mL for C. parapsilosis complex, and CFM50 of 16 μg/mL and 32 μg/mL, respectively. The association between 2-bromo-N-phenylacetamide and fluconazole did not show synergism or antagonism, being characterized as indifferent. Therefore, the present study revealed that in the year 2017, the majority of cases of invasive candidiasis came from inpatients in the intensive care unit of the university hospital, with C. albicans as the most common etiological agent and fluconazole as the only Candifast® kit which showed resistance (47%). In addition, this was the first study with the synthetic substance 2-bromo-N-phenylacetamide, which showed a strong fungicidal activity against clinical isolates of C. albicans and C. parapsilosis complex, however, this substance was indifferent when associated with fluconazole.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-08
2019-06-14
2021-01-02T21:51:35Z
2021-01-02T21:51:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/19093
url https://repositorio.ufpb.br/jspui/handle/123456789/19093
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
_version_ 1801843023510765568