Análise da atividade antifúngica in vitro de 2-bromo-N-fenilacetamida frente às espécies de Candida provenientes de um hospital universitário
Autor(a) principal: | |
---|---|
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 |