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      Prevalence and Fluconazole Susceptibility Profile of Candida spp. Clinical Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil

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          Abstract

          Candidiasis has become an important concern for clinical practice, especially with the increasing incidence of immunocompromised patients. In this scenario, the development resistance to fluconazole presents a challenge for treating these opportunistic infections. The aim of this study was to evaluate some epidemiology features of Candidainfections in a Brazilian University Hospital using data, previously unavailable. We observed that 44% of the 93 clinical isolates tested, belonged to Candida albicansspecies and 56% belonged to non-Candida albicansspecies (mainly Candida tropicalis and Candida glabrata). Most strains were isolated from urine samples where C. albicans was predominantly detected. 29 strains presented a fluconazole resistance phenotype and of these, 22 were chemosensitised by FK506, a classical inhibitor of ABC transporters related to azoles resistance. These data suggest the probable role of efflux pumps in this resistance phenotype. Our study highlights the need for developing effective control measures for fungal infections, rational use of antifungal drugs and development of new molecules able to abrogate the active transport of antifungals.

          Translated abstract

          A candidíase tem se tornado uma importante preocupação para a prática clínica, especialmente com o aumento da incidência de pacientes imunocomprometidos. Neste cenário, o desenvolvimento da resistência ao fluconazol se apresenta como um desafio ao tratamento dessas infecções oportunistas. O objetivo deste estudo consistiu em avaliar alguns aspectos epidemiológicos das infecções por Candida em um hospital universitário brasileiro, utilizando dados, anteriormente, indisponíveis. Nós observamos que 44% dos 93 isolados clínicos testados pertenciam à espécie Candida albicans e 56%, a espécies Candidanão-albicans (principalmente Candida tropicalise Candida glabrata). A maioria das cepas foi isolada de amostras de urina, onde C. albicans foi predominantemente detectada. 29 cepas apresentaram um fenótipo de resistência ao fluconazol e destas, 22 foram quimiosensibilizadas pelo FK506, um inibidor clássico dos transportadores ABC, envolvidos na resistência aos azóis. Estes dados sugerem a provável participação das bombas de efluxo nesse fenótipo de resistência. Nosso estudo ressalta a necessidade do desenvolvimento de medidas de controle efetivas para as infecções fúngicas, o uso racional de antifúngicos e o desenvolvimento de novas moléculas capazes de inibir o transporte ativo de antifúngicos.

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          Most cited references58

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          Attributable mortality of nosocomial candidemia, revisited.

          We reexamined the attributable mortality of nosocomial candidemia 15 years after a retrospective cohort study performed at our hospital demonstrated an attributable mortality of 38%. For all episodes of nosocomial candidemia between 1 July 1997 and 30 June 2001, we matched control patients with case patients by age, sex, date of hospital admission, underlying disease(s), length of time at risk, and surgical procedure(s). We analyzed 108 matched pairs. There were no statistically significant differences in age, sex, underlying disease(s), time at risk, surgical procedure, or vital signs at admission between cases and controls. The crude mortality among case patients was 61% (66 of 108 patients), compared with 12% (13 of 108) among control patients, for an attributable mortality of 49% (95% CI, 38%-60%). Nosocomial candidemia is still associated with an extremely high crude and attributable mortality--much higher than that expected from underlying disease alone.
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            Epidemiology and Outcomes of Invasive Candidiasis Due to Non-albicans Species of Candida in 2,496 Patients: Data from the Prospective Antifungal Therapy (PATH) Registry 2004–2008

            This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance) registry from 2004 to 2008. A total of 2,496 patients with non-albicans species of Candida isolates were identified. The identified species were C. glabrata (46.4%), C. parapsilosis (24.7%), C. tropicalis (13.9%), C. krusei (5.5%), C. lusitaniae (1.6%), C. dubliniensis (1.5%) and C. guilliermondii (0.4%); 111 infections involved two or more species of Candida (4.4%). Non-albicans species accounted for more than 50% of all cases of invasive candidiasis in 15 of the 24 sites (62.5%) that contributed more than one case to the survey. Among solid organ transplant recipients, patients with non-transplant surgery, and patients with solid tumors, the most prevalent non-albicans species was C. glabrata at 63.7%, 48.0%, and 53.8%, respectively. In 1,883 patients receiving antifungal therapy on day 3, fluconazole (30.5%) and echinocandins (47.5%) were the most frequently administered monotherapies. Among the 15 reported species, 90-day survival was highest for patients infected with either C. parapsilosis (70.7%) or C. lusitaniae (74.5%) and lowest for patients infected with an unknown species (46.7%) or two or more species (53.2%). In conclusion, this study expands the current knowledge of the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in North America. The variability in species distribution in these centers underscores the importance of local epidemiology in guiding the selection of antifungal therapy.
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              Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain.

              A prospective, multicentre, population-based surveillance programme for Candida bloodstream infections was implemented in five metropolitan areas of Spain to determine its incidence and the prevalence of antifungal resistance, and to identify predictors of death. Between May 2010 and April 2011, Candida isolates were centralized to a reference laboratory for species identification by DNA sequencing and for susceptibility testing by EUCAST reference procedure. Prognostic factors associated with early (0-7 days) and late (8-30 days) death were analysed using logistic regression modelling. We detected 773 episodes: annual incidence of 8.1 cases/100 000 inhabitants, 0.89/1000 admissions and 1.36/10 000 patient-days. Highest incidence was found in infants younger than 1 year (96.4/100 000 inhabitants). Candida albicans was the predominant species (45.4%), followed by Candida parapsilosis (24.9%), Candida glabrata (13.4%) and Candida tropicalis (7.7%). Overall, 79% of Candida isolates were susceptible to fluconazole. Cumulative mortality at 7 and 30 days after the first episode of candidaemia was 12.8% and 30.6%, respectively. Multivariate analysis showed that therapeutic measures within the first 48 h may improve early mortality: antifungal treatment (OR 0.51, 95% CI 0.27-0.95) and central venous catheter removal (OR 0.43, 95% CI 0.21-0.87). Predictors of late death included host factors (e.g. patients' comorbid status and signs of organ dysfunction), primary source (OR 1.63, 95% CI 1.03-2.61), and severe sepsis or septic shock (OR 1.77, 95% CI 1.05-3.00). In Spain, the proportion of Candida isolates non-susceptible to fluconazole is higher than in previous reports. Early mortality may be improved with strict adherence to guidelines. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                aabc
                Anais da Academia Brasileira de Ciências
                An. Acad. Bras. Ciênc.
                Academia Brasileira de Ciências (Rio de Janeiro )
                1678-2690
                August 2015
                : 87
                : 2 suppl
                : 1349-1359
                Affiliations
                [1 ] Universidade Federal do Rio de Janeiro Brazil
                [2 ] Universidade Federal de Juiz de Fora Brazil
                Article
                S0001-37652015000301349
                10.1590/0001-3765201520140717
                ec51aeb9-5784-4c3d-96dc-ac9f5a5162e5

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0001-3765&lng=en
                Categories
                MULTIDISCIPLINARY SCIENCES

                epidemiologia,fluconazol,resistência,Candidaspp.,clinical isolates,epidemiology,fluconazole,resistance,Candidaspp,isolados clínicos

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