Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/5906 |
Resumo: | Widespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, similar phenomenon has been observed for Candida glabrata, specie that has emerged as a pathogen of clinical importance. Fluconazole resistance has been clinically described in Candida glabrata isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. glabrata isolates were evaluated. One group was composed by fluconazole-susceptible clinical isolates (FS), and the other was composed by fluconazole-resistant (FR) laboratory derivatives from the former through an in vitro method of fluconazole resistance induction, in order to compare the activitie of the three major antifungal agent classes azoles, echinocandins and poliens. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL. All yeasts were tested by the broth microdilution method. Based on susceptibility parameters (MIC range, MIC50, MIC90 and geometric mean), the fluconazole-susceptible C. glabrata group (FS) was susceptible to amphotericin B (MIC90 of 0.125 μg/ml). For inhibition, the fluconazole-resistant C. glabrata group (FR) required higher concentrations of amphotericin B (MIC90 of 2 μg/ml). C. glabrata FR group showed cross-resistance with voriconazole (MIC90 of 16 μg/ml). Echinocandins showed the lowest MICs against to both group, flucoanzole-susceptible and resistant. Micafungin demostrated the lowest MIC values among all antifungal agents evaluated (MIC90 of 0.008 μg/ml in FS and 0.015 μg/ml in FR). Our results showed that resistance to fluconazole affected voriconazole susceptibility but not the echinocandin susceptibility, which demonstrated excellent activitie against tested C. glabrata groups. |
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2012-11-292012-11-292012-02-28MARIO, Débora Alves Nunes. Activity of echinocandins, anfotericin B and voriconazole against fluconazole-susceptible and - resistant Candida glabrata isolates. 2012. 80 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/5906Widespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, similar phenomenon has been observed for Candida glabrata, specie that has emerged as a pathogen of clinical importance. Fluconazole resistance has been clinically described in Candida glabrata isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. glabrata isolates were evaluated. One group was composed by fluconazole-susceptible clinical isolates (FS), and the other was composed by fluconazole-resistant (FR) laboratory derivatives from the former through an in vitro method of fluconazole resistance induction, in order to compare the activitie of the three major antifungal agent classes azoles, echinocandins and poliens. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL. All yeasts were tested by the broth microdilution method. Based on susceptibility parameters (MIC range, MIC50, MIC90 and geometric mean), the fluconazole-susceptible C. glabrata group (FS) was susceptible to amphotericin B (MIC90 of 0.125 μg/ml). For inhibition, the fluconazole-resistant C. glabrata group (FR) required higher concentrations of amphotericin B (MIC90 of 2 μg/ml). C. glabrata FR group showed cross-resistance with voriconazole (MIC90 of 16 μg/ml). Echinocandins showed the lowest MICs against to both group, flucoanzole-susceptible and resistant. Micafungin demostrated the lowest MIC values among all antifungal agents evaluated (MIC90 of 0.008 μg/ml in FS and 0.015 μg/ml in FR). Our results showed that resistance to fluconazole affected voriconazole susceptibility but not the echinocandin susceptibility, which demonstrated excellent activitie against tested C. glabrata groups.O uso prolongado e indiscriminado dos azólicos nos últimos anos permitiu um rápido desenvolvimento de resistência aos fármacos nas espécies de Candida. Em Candida albicans, a resistência ao fluconazol causa resistência cruzada a outros antifúngicos e aumento na virulência, tornando o tratamento ainda mais complicado por causa das opções terapêuticas limitadas. Ainda assim, fenômeno semelhante tem sido observado para Candida glabrata, espécie que emergiu como patógenos de importância clínica. A resistência ao fluconazol tem sido clinicamente descrita em isolados de Candida glabrata, e é facilmente induzida pela exposição in vitro ao azólico, mas pouco se conhece sobre suas conseqüências. No presente estudo, dois grupos de isolados de C. glabrata foram avaliados. Um grupo era composto de isolados clínicos sensíveis ao fluconazol (FS), e o outro, derivado do primeiro através de técnica de indução de resistência, era composto de isolados resistentes ao fluconazol (FR), com o intuito de comparar a atividade das três maiores classes de agentes antifúngicos azóis, equinocandinas e poliênicos. Os derivados resistentes obtidos evidenciaram concentrações inibitórias mínimas (CIMs) maiores ou iguais a 64 μg/mL. Foram realizados testes de suscetibilidade aos antifúngicos através da técnica de microdiluição em caldo. Com base nos parâmetros de suscetibilidade (faixa de CIM, CIM50, CIM90 e média geométrica), o grupo FS foi suscetível à anfotericina B (CIM90 de 0,125 μg/ml). Entretanto, o grupo FR requereu doses maiores do antifúngico para ser inibido (CIM90 de 2 μg/ml). O grupo de C. glabrata FR evidenciou resistência cruzada com voriconazol (CIM90 de 16 μg/ml). As equinocandinas mostraram os melhores resultados frente a ambos os grupos, sensíveis e resistentes. Micafungina demonstrou os menores valores de CIM entre todos os agentes antifúngicos estudados (CIM90 de 0.008 μg/ml para FS e 0.015 μg/ml para FR). Os resultados deste estudo mostraram que a resistência ao fluconazol afeta a suscetibilidade do voriconazol, mas não das equinocandinas, as quais mostraram excelente atividade frente aos grupos de C. glabrata testados.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBRFarmáciaCandida glabrataResistênciaFluconazolAgentes antifúngicosCandida glabrataResistanceFluconazoleAntifungal agentsCNPQ::CIENCIAS DA SAUDE::FARMACIAAtividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazolActivity of echinocandins, anfotericin B and voriconazole against fluconazole-susceptible and - resistant Candida glabrata isolatesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAlves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Linares, Carlos Eduardo Blancohttp://lattes.cnpq.br/8135690917054350Santurio, Janio Moraishttp://lattes.cnpq.br/6316012260769979http://lattes.cnpq.br/0731595522786356Mario, Débora Alves Nunes201000000000400500500300500bfe6016c-9c1e-42ca-ab1d-db5453ed090cbaf55de6-47bc-4c60-b985-412ab10daa0d0a1b2b40-34ce-4850-a5d0-084f07d01f70fcf059a8-da92-4056-88e2-8facd44a897ainfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALMARIO, DEBORA ALVES NUNES.pdfapplication/pdf527195http://repositorio.ufsm.br/bitstream/1/5906/1/MARIO%2c%20DEBORA%20ALVES%20NUNES.pdf219d87b13ca78f4f052762c53259ecaaMD51TEXTMARIO, DEBORA ALVES NUNES.pdf.txtMARIO, DEBORA ALVES NUNES.pdf.txtExtracted texttext/plain153364http://repositorio.ufsm.br/bitstream/1/5906/2/MARIO%2c%20DEBORA%20ALVES%20NUNES.pdf.txt5fe3a493f2ef1864534a317f1d823496MD52THUMBNAILMARIO, DEBORA ALVES NUNES.pdf.jpgMARIO, DEBORA ALVES NUNES.pdf.jpgIM Thumbnailimage/jpeg4893http://repositorio.ufsm.br/bitstream/1/5906/3/MARIO%2c%20DEBORA%20ALVES%20NUNES.pdf.jpgd0fff8f63370ff921837f17b95201520MD531/59062023-06-15 11:46:12.508oai:repositorio.ufsm.br:1/5906Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-06-15T14:46:12Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
dc.title.alternative.eng.fl_str_mv |
Activity of echinocandins, anfotericin B and voriconazole against fluconazole-susceptible and - resistant Candida glabrata isolates |
title |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
spellingShingle |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol Mario, Débora Alves Nunes Candida glabrata Resistência Fluconazol Agentes antifúngicos Candida glabrata Resistance Fluconazole Antifungal agents CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
title_full |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
title_fullStr |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
title_full_unstemmed |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
title_sort |
Atividade das equinocandinas, anfotericina B e voriconazol frente a isolados de Candida glabrata sensíveis e resistentes ao fluconazol |
author |
Mario, Débora Alves Nunes |
author_facet |
Mario, Débora Alves Nunes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Alves, Sydney Hartz |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0330782478769631 |
dc.contributor.referee1.fl_str_mv |
Linares, Carlos Eduardo Blanco |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/8135690917054350 |
dc.contributor.referee2.fl_str_mv |
Santurio, Janio Morais |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6316012260769979 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0731595522786356 |
dc.contributor.author.fl_str_mv |
Mario, Débora Alves Nunes |
contributor_str_mv |
Alves, Sydney Hartz Linares, Carlos Eduardo Blanco Santurio, Janio Morais |
dc.subject.por.fl_str_mv |
Candida glabrata Resistência Fluconazol Agentes antifúngicos |
topic |
Candida glabrata Resistência Fluconazol Agentes antifúngicos Candida glabrata Resistance Fluconazole Antifungal agents CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Candida glabrata Resistance Fluconazole Antifungal agents |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Widespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, similar phenomenon has been observed for Candida glabrata, specie that has emerged as a pathogen of clinical importance. Fluconazole resistance has been clinically described in Candida glabrata isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. glabrata isolates were evaluated. One group was composed by fluconazole-susceptible clinical isolates (FS), and the other was composed by fluconazole-resistant (FR) laboratory derivatives from the former through an in vitro method of fluconazole resistance induction, in order to compare the activitie of the three major antifungal agent classes azoles, echinocandins and poliens. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL. All yeasts were tested by the broth microdilution method. Based on susceptibility parameters (MIC range, MIC50, MIC90 and geometric mean), the fluconazole-susceptible C. glabrata group (FS) was susceptible to amphotericin B (MIC90 of 0.125 μg/ml). For inhibition, the fluconazole-resistant C. glabrata group (FR) required higher concentrations of amphotericin B (MIC90 of 2 μg/ml). C. glabrata FR group showed cross-resistance with voriconazole (MIC90 of 16 μg/ml). Echinocandins showed the lowest MICs against to both group, flucoanzole-susceptible and resistant. Micafungin demostrated the lowest MIC values among all antifungal agents evaluated (MIC90 of 0.008 μg/ml in FS and 0.015 μg/ml in FR). Our results showed that resistance to fluconazole affected voriconazole susceptibility but not the echinocandin susceptibility, which demonstrated excellent activitie against tested C. glabrata groups. |
publishDate |
2012 |
dc.date.accessioned.fl_str_mv |
2012-11-29 |
dc.date.available.fl_str_mv |
2012-11-29 |
dc.date.issued.fl_str_mv |
2012-02-28 |
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.citation.fl_str_mv |
MARIO, Débora Alves Nunes. Activity of echinocandins, anfotericin B and voriconazole against fluconazole-susceptible and - resistant Candida glabrata isolates. 2012. 80 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/5906 |
identifier_str_mv |
MARIO, Débora Alves Nunes. Activity of echinocandins, anfotericin B and voriconazole against fluconazole-susceptible and - resistant Candida glabrata isolates. 2012. 80 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
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http://repositorio.ufsm.br/handle/1/5906 |
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por |
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por |
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Universidade Federal de Santa Maria |
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UFSM |
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Farmácia |
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Universidade Federal de Santa Maria |
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