Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos

Detalhes bibliográficos
Autor(a) principal: Alves, Izabel Almeida
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/5928
Resumo: In the last decades the invasive mycoses caused by opportunistic fungi has showed a significant growth. The extensive use of azoles showed that the development of resistance of Candida species to these drugs is an emergent phenomenon. C. glabrata typically presents high degree of primary resistance to fluconazole what determine additional difficulties in the therapies. Here two groups of C. glabrata isolates were evaluated: the first formed by strains primarily fluconazole-susceptible and the second generated by the first, was composed by the same isolates after induction of the fluconazole-resistance. The susceptibility tests detected even in the first group, strains azole-resistant as against itraconazole and voriconazole. The induction of resistance to fluconazole was carried out in order to compare the susceptibilities between the two groups against combined drugs. The fluconazole-resistant strains (Group 2) showed MIC ≥ 64 μg/ml and cross-resistance was either detected with fluconazole, voriconazole and itraconazole as well as to other antifungal agents as amphotericin B and caspofungine. The more frequent interaction observed was indifference, however important synergisms were showed against fluconazole-resistant isolates. The best synergism was registered with amphotericin B+ flucytosine (G1 = 61,77% and G2=76,47%). Other synergistic interactions were amphotericin B+ketoconazole (G2=73,53%), amphotericin B+voriconazole (G2=55,88%), amphotericin B+voricoonazole (G2=55,88%), all of them without antagonisms. The highest percentage of the antagonism were observed with ketoconazole+flucytosine (G1=61,77% and G2= 55,88%).
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spelling 2013-05-132013-05-132011-03-25ALVES, Izabel Almeida. AVALIAÇÃO DA SUSCETIBILIDADE DE Candida glabrata RESISTENTES AO FLUCONAZOL FRENTE A COMBINAÇÕES DE ANTIFÚNGICOS. 2011. 82 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2011.http://repositorio.ufsm.br/handle/1/5928In the last decades the invasive mycoses caused by opportunistic fungi has showed a significant growth. The extensive use of azoles showed that the development of resistance of Candida species to these drugs is an emergent phenomenon. C. glabrata typically presents high degree of primary resistance to fluconazole what determine additional difficulties in the therapies. Here two groups of C. glabrata isolates were evaluated: the first formed by strains primarily fluconazole-susceptible and the second generated by the first, was composed by the same isolates after induction of the fluconazole-resistance. The susceptibility tests detected even in the first group, strains azole-resistant as against itraconazole and voriconazole. The induction of resistance to fluconazole was carried out in order to compare the susceptibilities between the two groups against combined drugs. The fluconazole-resistant strains (Group 2) showed MIC ≥ 64 μg/ml and cross-resistance was either detected with fluconazole, voriconazole and itraconazole as well as to other antifungal agents as amphotericin B and caspofungine. The more frequent interaction observed was indifference, however important synergisms were showed against fluconazole-resistant isolates. The best synergism was registered with amphotericin B+ flucytosine (G1 = 61,77% and G2=76,47%). Other synergistic interactions were amphotericin B+ketoconazole (G2=73,53%), amphotericin B+voriconazole (G2=55,88%), amphotericin B+voricoonazole (G2=55,88%), all of them without antagonisms. The highest percentage of the antagonism were observed with ketoconazole+flucytosine (G1=61,77% and G2= 55,88%).A freqüência de micoses invasivas devido a fungos oportunistas tem evidenciado significativo aumento nas duas últimas décadas. O uso prolongado e indiscriminado dos azólicos evidenciou o desenvolvimento de resistência a estes fármacos nas espécies de Candida. A espécie C. glabrata caracteriza-se por elevados percentuais de resistência primária ao fluconazol fato que determina dificuldades terapêuticas adicionais. No presente estudo, dois grupos de isolados de C. glabrata foram avaliados: o primeiro formado por isolados clínicos sensíveis ao fluconazol, e o segundo, derivado do primeiro, foi formado pelos mesmos isolados, após terem sido induzidos a resistência ao fluconazol in vitro. Mesmo neste grupo de C. glabrata sensíveis ao fluconazol, os testes de suscetibilidade já evidenciaram resistência frente a outros azólicos como ao itraconazol e voriconazol. Os derivados resistentes ao fluconazol evidenciaram concentrações inibitórias mínimas maiores ou iguais a 64 g/mL. Neste grupo de isolados fluconazol-resistentes, os testes de suscetibilidade detectaram resistência cruzada com cetoconazol, voriconazol e itraconazol bem como com outros agentes de outras classes como a anfotericina B e caspofungina. A indução da resistência foi realizada com o objetivo de se comparar a suscetibilidade entre os dois grupos, frente a fármacos combinados. As associações de antifúngicos entre os grupos sensíveis e resistentes ao fluconazol resultaram, em maior parte, interações indiferentes. No entando as associações mostraram-se mais eficazes nos isolados resistentes ao fluconazol. Em ambos os grupos, a combinação que resultou em maior sinergismo foi anfotericina B com flucitosina (.G1 = 61,77%.% e G2 = 76,47%); outras combinações sinérgicas foram anfotericina B + cetoconazol (G2 = 73,53%), anfotericina B + voriconazol (G2 = 55,88%), todos com ausência de antagonismo. Os maiores percentuais de antagonismo foram observados na combinação cetoconazol + flucitosina (G1 = 61,77% e G2 = 55,88%).Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBRFarmáciaCandida glabrataResistênciaFluconazolAntifúngicosCandida glabrataResistanceFluconazoleAntifungalsCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAlves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Lübeck, Irinahttp://lattes.cnpq.br/1405850939282996Botton, Sônia de Avilahttp://lattes.cnpq.br/0814772095155945http://lattes.cnpq.br/0091667422924639Alves, Izabel Almeida201000000000400500300300500bfe6016c-9c1e-42ca-ab1d-db5453ed090c5371c468-5eb2-4efb-aa4a-8478effff39087c17e65-897a-4810-8655-6317675be79a24806e8f-fdc9-4fdd-9936-d012e1f365bainfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALALVES, IZABEL ALMEIDA.pdfapplication/pdf683194http://repositorio.ufsm.br/bitstream/1/5928/1/ALVES%2c%20IZABEL%20ALMEIDA.pdfd1eedb0b3f7b5b69b87256113a2c7f3aMD51TEXTALVES, IZABEL ALMEIDA.pdf.txtALVES, IZABEL ALMEIDA.pdf.txtExtracted texttext/plain182305http://repositorio.ufsm.br/bitstream/1/5928/2/ALVES%2c%20IZABEL%20ALMEIDA.pdf.txt1fa2211191d2ebcb74bbd3088196cd8eMD52THUMBNAILALVES, IZABEL ALMEIDA.pdf.jpgALVES, IZABEL ALMEIDA.pdf.jpgIM Thumbnailimage/jpeg4851http://repositorio.ufsm.br/bitstream/1/5928/3/ALVES%2c%20IZABEL%20ALMEIDA.pdf.jpg28388ff1fa8488e4e5c57e79d4014d88MD531/59282022-10-10 12:19:52.392oai:repositorio.ufsm.br:1/5928Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-10-10T15:19:52Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
title Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
spellingShingle Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
Alves, Izabel Almeida
Candida glabrata
Resistência
Fluconazol
Antifúngicos
Candida glabrata
Resistance
Fluconazole
Antifungals
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
title_full Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
title_fullStr Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
title_full_unstemmed Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
title_sort Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos
author Alves, Izabel Almeida
author_facet Alves, Izabel Almeida
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 Lübeck, Irina
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/1405850939282996
dc.contributor.referee2.fl_str_mv Botton, Sônia de Avila
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0814772095155945
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0091667422924639
dc.contributor.author.fl_str_mv Alves, Izabel Almeida
contributor_str_mv Alves, Sydney Hartz
Lübeck, Irina
Botton, Sônia de Avila
dc.subject.por.fl_str_mv Candida glabrata
Resistência
Fluconazol
Antifúngicos
topic Candida glabrata
Resistência
Fluconazol
Antifúngicos
Candida glabrata
Resistance
Fluconazole
Antifungals
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Candida glabrata
Resistance
Fluconazole
Antifungals
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description In the last decades the invasive mycoses caused by opportunistic fungi has showed a significant growth. The extensive use of azoles showed that the development of resistance of Candida species to these drugs is an emergent phenomenon. C. glabrata typically presents high degree of primary resistance to fluconazole what determine additional difficulties in the therapies. Here two groups of C. glabrata isolates were evaluated: the first formed by strains primarily fluconazole-susceptible and the second generated by the first, was composed by the same isolates after induction of the fluconazole-resistance. The susceptibility tests detected even in the first group, strains azole-resistant as against itraconazole and voriconazole. The induction of resistance to fluconazole was carried out in order to compare the susceptibilities between the two groups against combined drugs. The fluconazole-resistant strains (Group 2) showed MIC ≥ 64 μg/ml and cross-resistance was either detected with fluconazole, voriconazole and itraconazole as well as to other antifungal agents as amphotericin B and caspofungine. The more frequent interaction observed was indifference, however important synergisms were showed against fluconazole-resistant isolates. The best synergism was registered with amphotericin B+ flucytosine (G1 = 61,77% and G2=76,47%). Other synergistic interactions were amphotericin B+ketoconazole (G2=73,53%), amphotericin B+voriconazole (G2=55,88%), amphotericin B+voricoonazole (G2=55,88%), all of them without antagonisms. The highest percentage of the antagonism were observed with ketoconazole+flucytosine (G1=61,77% and G2= 55,88%).
publishDate 2011
dc.date.issued.fl_str_mv 2011-03-25
dc.date.accessioned.fl_str_mv 2013-05-13
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dc.identifier.citation.fl_str_mv ALVES, Izabel Almeida. AVALIAÇÃO DA SUSCETIBILIDADE DE Candida glabrata RESISTENTES AO FLUCONAZOL FRENTE A COMBINAÇÕES DE ANTIFÚNGICOS. 2011. 82 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2011.
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/5928
identifier_str_mv ALVES, Izabel Almeida. AVALIAÇÃO DA SUSCETIBILIDADE DE Candida glabrata RESISTENTES AO FLUCONAZOL FRENTE A COMBINAÇÕES DE ANTIFÚNGICOS. 2011. 82 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2011.
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