Navegando por Palavras-chave "Fluconazole resistance"
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- ItemSomente MetadadadosFirst report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia(W B Saunders Co Ltd, 2016) Calvo, Belinda; Melo, Analy Salles de Azevedo [UNIFESP]; Perozo-Mena, Armindo; Hernandez, Martin; Francisco, Elaine Cristina [UNIFESP]; Hagen, Ferry; Meis, Jacques F.; Colombo, Arnaldo Lopes [UNIFESP]Objectives: Characterization of a hospital outbreak of Candida auris candidemia that involved 18 critically ill patients in Venezuela. Method: Bloodstream isolates of C. auris obtained from 18 patients admitted at a medical center in Maracaibo, between March, 2012 and July, 2013 were included. Species identification was confirmed by ITS rDNA sequencing. Isolates were subsequently typed by amplified fragment length polymorphism fingerprinting (AFLP). Susceptibility testing was performed according to CLSI. Clinical data were collected from all cases by using a standard clinical form. Results: A total of 13 critically ill pediatric and 5 adult patients, with a median age of 26 days, were included. All were previously exposed to antibiotics and multiple invasive medical procedures. Clinical management included prompt catheter removal and antifungal therapy. Thirteen patients (72%) survived up to 30 days after onset of candidemia. AFLP fingerprinting of all C. auris isolates suggested a clonal outbreak. The isolates were considered resistant to azoles, but susceptible to anidulafungin and 50% of isolates exhibited amphotericin B MIC values of >1 mu g/ml. Conclusions: The study demonstrated that C. auris is a multiresistant yeast pathogen that can be a source of health-care associated infections in tertiary care hospitals with a high potential for nosocomial horizontal transmission. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
- ItemSomente MetadadadosOutbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit(Biomed Central Ltd, 2016) Sampaio Pinhati, Henrique Marconi; Casulari, Luiz Augusto; Remondi Souza, Ana Carolina [UNIFESP]; Siqueira, Ricardo Andreotti [UNIFESP]; Gomes Damasceno, Camila Maria; Colombo, Arnaldo Lopes [UNIFESP]Background: Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. Methods: This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. Results: We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. Conclusions: The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.
- ItemAcesso aberto (Open Access)Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae(Biomed Central Ltd, 2014-07-26) Reis de Sa, Leandro Figueira; Toledo, Fabiano Travanca; Sousa, Bruno Artur de; Goncalves, Augusto Cesar; Tessis, Ana Claudia; Wendler, Edison P.; Comasseto, Joao V. [UNIFESP]; Dos Santos, Alcindo A.; Ferreira-Pereira, Antonio; Universidade Federal do Rio de Janeiro (UFRJ); Universidade de São Paulo (USP); Inst Fed Educ Ciencia & Tecnol Rio de Janeiro IFR; Universidade Federal de São Paulo (UNIFESP)Background: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. the Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. the present study investigated the effects of 13 synthetic compounds on Pdr5p.Results: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 M and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 mu M. When tested at 100 mu M, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans.Conclusions: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.