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Pesquisa : D03.383.129 [Categoria DeCS]
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Id: biblio-839188
Autor: Gonzalez, Javier M; Rodriguez, Carlos A; Agudelo, Maria; Zuluaga, Andres F; Vesga, Omar.
Título: Antifungal pharmacodynamics: Latin America's perspective
Fonte: Braz. j. infect. dis;21(1):79-87, Jan.-Feb. 2017. tab, graf.
Idioma: en.
Projeto: Universidad de Antioquia.
Resumo: Abstract The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed.
Descritores: Antifúngicos/farmacocinética
-Polienos/uso terapêutico
Polienos/farmacocinética
Aspergilose/metabolismo
Aspergilose/tratamento farmacológico
Azóis/uso terapêutico
Azóis/farmacocinética
Triazóis/uso terapêutico
Triazóis/farmacocinética
Candidíase/metabolismo
Candidíase/tratamento farmacológico
Testes de Sensibilidade Microbiana
Área Sob a Curva
Relação Dose-Resposta a Droga
Equinocandinas/uso terapêutico
Equinocandinas/farmacocinética
América Latina
Antifúngicos/uso terapêutico
Limites: Humanos
Tipo de Publ: Revisão
Revisão Sistemática
Responsável: BR1.1 - BIREME


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Id: lil-398659
Autor: Peria, Monica Mencaroni Ferreira.
Título: Prevalência de fenótipos-resistentes e espécies emergentes de leveduras e alga associadas a vulvovaginites / Prevalence of resistant phenotypes and emerging species of yeasts and algae associate to vulvovaginitis.
Fonte: São Paulo; s.n; 2003. [54] p. ilus, tab, graf.
Idioma: pt.
Tese: Apresentada a São Paulo (Estado). Secretaria da Saúde. Coordenação dos Institutos de Pesquisa. Programa de Pós-Graduação em Ciências para obtenção do grau de Mestre.
Resumo: Candidíase é a segunda causa de corrimento vaginal, e no Brasil está incluída na abordagem sindrômica para o tratamento de doenças sexualmente transmissíveis (DST,no Programa Nacional de Controle de DST/AIDS do Ministério da Saúde. Estima-se que 75% das mulheres adultas irão manifestar pelo menos um episódio da doença em alguma ocasião de suas vidas. Em pelo menos 5% a 10% dessas infecções, pode haver recorrência. Para entender melhor a ocorrência de vulvovaginites, este trabalho itendificou gênero e espécies de levedura e alga aclorofilada associadas a esse quadro e analisou o perfil de sensibilidade das amostras de secreção vaginal de 300 mulhares. Dados clínicos foram obtidos de 134 casos. Os resultados mostraram a prevalência de Candida albicans em 244 (81,34%) das amostras e outros gêneros e espécies prevaleceram em 56 (18,66%) das amostras, entre eles estão: Trichosporon asahii n= (0,67%), Trichosporon inkin n=1 (0,33%), Saccharomyces cerevisiae n=2 (0,67%), Prototheca wickerhamii n=1 (0,33%), Rhodotorula mucilaginosa n=1 (0,33%), Candida vinara n=1 (0,33%), Candida famata n=1 (0,33%). O perfil de sensibilidade foi feito segundo o documento do NCCLS M27A com modificações sugeridas pelo EUCAST. Os resultados demonstraram fenótipos resistentes a fluconazol, itraconazol e anfotericina B em 3,96% das amostras. Sensibilidade dependente da droga (SDD) em 10,65% das amostras para itraconazol e fluconazol. Todas as amostras de Candida parapsilosis, Candida Kefyr, Candida vinara e Prototheca wickerwamii foram sensíveis aos azois e anfotericina B. Apenas uma amostra de Trichosporon asahii apresentou resistência a anfotericina B (MIC=4ug/mL). Microorganismos novos e fenótipos resistentes ou SDD,que são incomuns aos clínicos, foram relatados neste trabalho.A exposição rotineira de muitas pacientes à abordagen sindrômica e o aumento de infecções por HIV entre as mulheres, pode promover o potencial oportunista destas espécies. Nossos dados enfatizam a importância de identificar e analisar o perfil de sensibilidade dos agentes associados a vulvovaginites...
Descritores: Leveduras
Sintomas em Homeopatia
Antifúngicos
Azóis
Candidíase Vulvovaginal
-Fenótipo
Candidíase Cutânea
Doenças Sexualmente Transmissíveis/terapia
Responsável: BR91.2 - Centro de Documentação
BR91.2; W4, P441p, 2003


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Id: lil-260933
Autor: Lago, Marcos Junqueira do; Carvalho, Eduardo da Silva.
Título: Drogas antifúngicas / Antifungal drugs
Fonte: In: Farhat, Calil Kairalla; Carvalho, Eduardo da Silva; Carvalho, Luiza Helena Falleiros Rodrigues; Succi, Regina Célia de Menezes. Infectologia pediátrica. Säo Paulo, Atheneu, 1998. p.650-6, tab.
Idioma: pt.
Descritores: Pediatria
Antifúngicos/uso terapêutico
-Fluconazol/uso terapêutico
Anfotericina B/uso terapêutico
Itraconazol/uso terapêutico
Alilamina/uso terapêutico
Flucitosina/uso terapêutico
Micoses/terapia
Antifúngicos/farmacocinética
Azóis/uso terapêutico
Limites: Humanos
Responsável: BR31.1 - SIDC - Serviço de Informação e Documentação Científica
BR31.1; WC100, F225i, 2 ed.,1998


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Id: biblio-828186
Autor: Ellepola, Arjuna N. B; Samaranayake, L. P; Khan, Z. U.
Título: Extracellular phospholipase production of oral Candida albicans isolates from smokers, diabetics, asthmatics, denture wearers and healthy individuals following brief exposure to polyene, echinocandin and azole antimycotics
Fonte: Braz. j. microbiol;47(4):911-916, Oct.-Dec. 2016. tab.
Idioma: en.
Projeto: Kuwait University Research Grant.
Resumo: Abstract Objective Candida albicans is the primary causative agent of oral candidosis, and one of its key virulent attributes is considered to be its ability to produce extracellular phospholipases that facilitate cellular invasion. Oral candidosis can be treated with polyenes, and azoles, and the more recently introduced echinocandins. However, once administered, the intraoral concentration of these drugs tend to be sub-therapeutic and rather transient due to factors such as the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, the pathogenic yeasts may undergo a brief exposure to antifungal drugs. We, therefore, evaluated the phospholipase production of oral C. albicans isolates following brief exposure to sub-therapeutic concentrations of the foregoing antifungals. Materials and methods Fifty C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sub-therapeutic concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for one hour. Thereafter the drugs were removed and the phospholipase production was determined by a plate assay using an egg yolk-agar medium. Results The phospholipase production of these isolates was significantly suppressed with a percentage reduction of 10.65, 12.14, 11.45 and 6.40% following exposure to nystatin, amphotericin B, caspofungin and ketoconazole, respectively. This suppression was not significant following exposure to fluconazole. Conclusions Despite the sub-therapeutic, intra oral, bioavailability of polyenes, echinocandins and ketoconazole, they are likely to produce a persistent antifungal effect by suppressing phospholipase production, which is a key virulent attribute of this common pathogenic yeast.
Descritores: Fosfolipases/biossíntese
Candida albicans/efeitos dos fármacos
Candida albicans/metabolismo
Candidíase Bucal/microbiologia
Candidíase Bucal/tratamento farmacológico
Antifúngicos/farmacologia
-Polienos/uso terapêutico
Polienos/farmacologia
Azóis/uso terapêutico
Azóis/farmacologia
Candida albicans/isolamento & purificação
Candida albicans/patogenicidade
Fumar
Testes de Sensibilidade Microbiana
Dentaduras
Fatores de Virulência
Diabetes Mellitus
Ativação Enzimática
Espaço Extracelular
Equinocandinas/farmacologia
Antifúngicos/uso terapêutico
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: lil-762053
Autor: SHIKANAI-YASUDA, Maria Aparecida.
Título: Paracoccidioidomycosis treatment / Tratamento da paracoccidioidomicose
Fonte: Rev. Inst. Med. Trop. Säo Paulo;57(supl.19):31-37, Sept. 2015.
Idioma: en.
Projeto: Fundação de Amparo à Pesquisa do Estado de São Paulo.
Resumo: SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

RESUMOConsiderada micose endêmica emergente na América Latina, a paracoccidioidomicose é caracterizada por uma evolução crônica e envolvimento de múltiplos órgãos em pacientes com comprometimento imunológico. Sequelas da infecção estão relacionadas principalmente à insuficiência pulmonar e adrenal. A interação hospedeiro-parasito resulta em diferentes expressões da resposta imune dependendo da patogenicidade do parasito, carga fúngica e características genéticas do hospedeiro. Alguns estudos controlados e séries de casos têm demonstrado que azóis de ação rápida e derivados de sulfa constituem alternativas terapêuticas úteis nas formas mais leves da doença. Para casos moderados/graves, tratamentos mais prolongados ou mesmo por via parenteral são necessários especialmente quando há envolvimento de mucosa do trato digestivo, resultando em absorção deficiente de drogas. Embora estudos comparativos tenham relatado que esquemas terapêuticos mais curtos com itraconazol sejam capazes de induzir cura em pacientes cronicamente infectados, ainda existem desafios no tratamento, tais como a necessidade de maior número de estudos controlados envolvendo casos agudos, busca por novas drogas e combinações, compostos capazes de modular a resposta imune nos casos graves, e reações paradoxais.
Descritores: Paracoccidioidomicose/tratamento farmacológico
Sulfonamidas/uso terapêutico
Azóis/uso terapêutico
Anfotericina B/uso terapêutico
Antifúngicos/uso terapêutico
Naftalenos/uso terapêutico
-Índice de Gravidade de Doença
Resistência a Medicamentos
Ensaios Clínicos Controlados Aleatórios como Assunto
Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Revisão
Responsável: BR1.1 - BIREME


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Id: biblio-894913
Autor: Rocha, Debora Afonso Silva; Sa, Leandro Figueira Reis de; Pinto, Ana Carolina Cartagenes; Junqueira, Maria de Lourdes; Silva, Emiliana Mandarano da; Borges, Ronaldo Mohana; Ferreira-Pereira, Antonio.
Título: Characterisation of an ABC transporter of a resistant Candida glabrata clinical isolate
Fonte: Mem. Inst. Oswaldo Cruz;113(4):e170484, 2018. tab, graf.
Idioma: en.
Resumo: BACKGROUND Candida glabrata ranks second in epidemiological surveillance studies, and is considered one of the main human yeast pathogens. Treatment of Candida infections represents a contemporary public health problem due to the limited availability of an antifungal arsenal, toxicity effects and increasing cases of resistance. C. glabrata presents intrinsic fluconazole resistance and is a significant concern in clinical practice and in hospital environments. OBJECTIVE The aim of this study was to characterise the azole resistance mechanism presented by a C. glabrata clinical isolate from a Brazilian university hospital. METHODS Azole susceptibility assays, chemosensitisation, flow cytometry and mass spectrometry were performed. FINDINGS Our study demonstrated extremely high resistance to all azoles tested: fluconazole, voriconazole, posaconazole and itraconazole. This isolate was chemosensitised by FK506, a classical inhibitor of ABC transporters related to azole resistance, and Rhodamine 6G extrusion was observed. A mass spectrometry assay confirmed the ABC protein identification suggesting the probable role of efflux pumps in this resistance phenotype. MAIN CONCLUSIONS This study emphasizes the importance of ABC proteins and their relation to the resistance mechanism in hospital environments and they may be an important target for the development of compounds able to unsettle drug extrusion.
Descritores: Azóis/uso terapêutico
Candida glabrata/efeitos dos fármacos
Candida glabrata/metabolismo
-Espectrometria de Massas
Citometria de Fluxo
Responsável: BR1.1 - BIREME


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Id: biblio-889247
Autor: Guerra, Felipe QS; Araújo, Rodrigo SA; Sousa, Janiere P; Silva, Viviane A; Pereira, Fillipe O; Mendonça-Junior, Francisco JB; Barbosa-Filho, José M; Pereira, Julio Abrantes; Lima, Edeltrudes O.
Título: A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp
Fonte: Braz. j. microbiol;49(2):407-413, Apr.-June 2018. tab, graf.
Idioma: en.
Resumo: Abstract Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.
Descritores: Antifúngicos/isolamento & purificação
Antifúngicos/farmacologia
Aspergillus/efeitos dos fármacos
Cumarínicos/isolamento & purificação
Cumarínicos/farmacologia
Sinergismo Farmacológico
-Aspergillus/crescimento & desenvolvimento
Azóis/farmacologia
Membrana Celular/efeitos dos fármacos
Parede Celular/efeitos dos fármacos
Hifas/efeitos dos fármacos
Hifas/crescimento & desenvolvimento
Esporos Fúngicos/efeitos dos fármacos
Esporos Fúngicos/crescimento & desenvolvimento
Responsável: BR1.1 - BIREME


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Id: lil-777368
Autor: Silva, Danielly Beraldo dos Santos; Rodrigues, Luana Mireli Carbonera; Almeida, Adriana Araújo de; Oliveira, Kelly Mari Pires de; Grisolia/, Alexéia Barufatti.
Título: Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species
Fonte: Mem. Inst. Oswaldo Cruz;111(3):192-199, Mar. 2016. tab, graf.
Idioma: en.
Resumo: The azoles are the class of medications most commonly used to fight infections caused by Candida sp. Typically, resistance can be attributed to mutations in ERG11 gene (CYP51) which encodes the cytochrome P450 14α-demethylase, the primary target for the activity of azoles. The objective of this study was to identify mutations in the coding region of theERG11 gene in clinical isolates of Candidaspecies known to be resistant to azoles. We identified three new synonymous mutations in the ERG11 gene in the isolates of Candida glabrata (C108G, C423T and A1581G) and two new nonsynonymous mutations in the isolates of Candida krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of these nonsynonymous mutations was predicted using evolutionary conservation scores. The G524R mutation did not have effect on 14α-demethylase functionality, while the Y166S mutation was found to affect the enzyme. This observation suggests a possible link between the mutation and dose-dependent sensitivity to voriconazole in the clinical isolate of C. krusei. Although the presence of the Y166S in phenotype of reduced azole sensitivity observed in isolate C. kruseidemands investigation, it might contribute to the search of new therapeutic agents against resistant Candida isolates.
Descritores: Candida/efeitos dos fármacos
Candida/genética
Farmacorresistência Fúngica/genética
Mutação Puntual/efeitos dos fármacos
/genética
STEROL CONGENITAL ABNORMALITIES-DEMETHYLASE/genética
-Antifúngicos/farmacologia
Azóis/farmacologia
Candida glabrata/genética
Candida/classificação
Candida/isolamento & purificação
Relação Dose-Resposta a Droga
Genes Fúngicos
Haplótipos/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Filogenia
Voriconazol/farmacologia
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-775105
Autor: Brilhante, Raimunda S.N.; Paiva, Manoel A.N.; Sampaio, Célia M.S.; Castelo-Branco, Débora S.C.M.; Teixeira, Carlos E.C.; Alencar, Lucas P. de; Bandeira, Tereza J.P.G.; Monteiro, André J.; Cordeiro, Rossana A.; Pereira-Neto, Waldemiro A.; Sidrim, José J.C.; Moreira, José L.B.; Rocha, Marcos F.G..
Título: Azole resistance in Candida spp. isolated from Catú Lake, Ceará, Brazil: an efflux-pump-mediated mechanism
Fonte: Braz. j. microbiol;47(1):33-38, Jan.-Mar. 2016. tab, graf.
Idioma: en.
Projeto: CNPq; . CAPES.
Resumo: Abstract Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catú Lake, Ceará, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI). The minimum inhibitory concentrations (MICs) of amphotericin B, itraconazole, and fluconazole were 0.03125–2 µg/mL, 0.0625 to ≥16 µg/mL, and 0.5 to ≥64 µg/mL, respectively, and 13 resistant azole-resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps.
Descritores: Antifúngicos/metabolismo
Azóis/metabolismo
Candida/efeitos dos fármacos
Candida/isolamento & purificação
Farmacorresistência Fúngica
Lagos/microbiologia
-Transporte Biológico Ativo
Brasil
Testes de Sensibilidade Microbiana
Responsável: BR1.1 - BIREME


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ALVES, Sydney Hartz
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Id: lil-748244
Autor: Denardi, Laura Bedin; Mario, Débora Alves Nunes; Loreto, Érico Silva; Santurio, Janio Morais; Alves, Sydney Hartz.
Título: Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates
Fonte: Braz. j. microbiol;46(1):125-129, 05/2015. tab.
Idioma: en.
Resumo: In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.
Descritores: Antifúngicos/farmacologia
Azóis/farmacologia
Candida glabrata/efeitos dos fármacos
Sinergismo Farmacológico
Tacrolimo/farmacologia
-Candida glabrata/isolamento & purificação
Candidíase/microbiologia
Farmacorresistência Bacteriana
Testes de Sensibilidade Microbiana
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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