Fluconazole resistance

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    Fluconazole resistance


    Objective: In serial Cryptococcal isolates cultured from fresh cerebrospinal fluid (CSF) collected using lumbar punctures within a prospective clinical observational study in Tanzanian HIV-infected patients with cryptococcal meningitis (CM): 1. To characterise for the first time the prevalence of heteroresistance to fluconazole in pre- and on-treatment Cryptococcal isolates in human CM 2. To assess the selection for resistant subpopulations during the course of induction therapy of human CM using fluconazole alone or in combination with flucytosine (5FC) 3. To determine the molecular mechanism of fluconazole resistance Methods: Patients received fluconazole monotherapy at 800–1200 mg/d (n = 12), or in combination with 5FC (100 mg/kg/d) (n = 8). CSF was plated immediately onto unselected and fluconazole-containing media, and both total CFU/ml and the resistant subpopulation in the CSF were measured on days 1, 7 and 14 of treatment, and at any clinical relapse. Saved Cryptococcal isolates underwent extensive in vitro phenotypic characterisation including population assay profiling (PAP) to determine the area under the curve (AUC) of heteroresistance for each isolate, and drug efflux pump activity using the rhodamine-6 G assay. Whole genome next-generation DNA sequencing was performed on all isolates, including unselected colonies and heteroresistant colonies (growing on drug). Strains is a significant problem after long-term treatment of recurrent oropharyngeal candidiasis (OPC) in acquired immunodeficiency syndrome (AIDS) patients. Resistance can be caused by alterations in sterol biosynthesis, by mutations in the drug target enzyme, sterol 14α-demethylase (14DM), which lower its affinity for fluconazole, by increased expression of the strains, but overexpressed in many fluconazole-resistant clinical isolates, resulting in reduced intracellular fluconazole accumulation.

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    PublishedDecember 03, 1988DOIhttps//doi.org/10.1016/S0140-67368892919-4 · FLUCONAZOLE RESISTANCE IN CANDIDA GLABRATA · Previous. Fluconazole Resistance Candida albicans in Females With Recurrent Vaginitis and Pir1 Overexpression, Jundishapur J Microbiol. 2015 ; 89e21468. doi. Fluconazole resistance can be caused by mutations in the drug target, by changes in the sterol biosynthesis pathway, and by gain-of-function mutations in.

    Annotation score:3 out of 5 The annotation score provides a heuristic measure of the annotation content of a Uni Prot KB entry or proteome. This score cannot be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein. This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed. This subsection of the Names and taxonomy section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’. This subsection of the Names and taxonomy section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’. This subsection of the Names and taxonomy section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first. This subsection of the Names and taxonomy section is present for entries that are part of a proteome, i.e. Cyclic redundancy and other checksums Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)) This subsection of the ‘Entry information’ section provides a mnemonic identifier for a Uni Prot KB entry, but it is not a stable identifier. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced. This subsection of the 'Subcellular location' section describes the extent of a membrane-spanning region of the protein. Each reviewed entry is assigned a unique entry name upon integration into Uni Prot KB/Swiss-Prot. This subsection of the ‘Entry information’ section provides one or more accession number(s). Fluconazole is very effective in the treatment of oral thrush, but an increasing number of patients with recurrent oropharyngeal candidiasis have developed fluconazole-resistant yeasts following repeated courses of fluconazole therapy. Fluconazole resistance can develop in a single persistent strain of yeast, but more commonly fluconazole resistance results from emergence of a different Candida albicans strain or another Candida species. Higher doses of fluconazole are more effective against resistant strains in murine candidiasis, but the utility of identifying resistant isolates and treating resistant yeasts with high doses of fluconazole is not established. Thus, the objectives of this proposal are to define prospectively the epidemiology of fluconazole-resistant oropharyngeal candidiasis, to correlate therapeutic response with fluconazole resistance, and to evaluate the role of higher doses of fluconazole in treating resistant yeasts. These objectives will be achieved by longitudinally evaluating patients with HIV infection/AIDS treated with fluconazole for recurrent oropharyngeal candidiasis. The goal of these studies is to improve the treatment of oropharyngeal candidiasis in patients with HIV infection/AIDS. The specific aims of this proposal are: 1) To longitudinally evaluate a cohort of patients with recurrent oropharyngeal candidiasis for the development of fluconazole resistance and to correlate that resistance with clinical response to therapy; 2) To establish strain identity using molecular characterization of the yeasts in order to establish the epidemiology of fluconazole- resistant oropharyngeal candidiasis; 3) To correlate antifungal susceptibility testing with clinical outcome and to determine the utility of screening susceptibility techniques to detect fluconazole resistant yeasts; 4) To evaluate high doses of fluconazole against resistant yeasts in a murine model of candidiasis; 5) To determine the clinical utility of high doses of fluconazole in treating patients with fluconazole-resistant yeasts.

    Fluconazole resistance

    Fluconazole-Resistant Candida albicans Vulvovaginitis, Fluconazole Resistance Candida albicans in Females With.

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  7. A case was defined as fluconazole-resistant by the presence of clinical features suggestive of persistence or relapse of infection despite fluconazole therapy, with or without supporting laboratory evidence of reduced susceptibility to fluconazole.

    • Fluconazole resistance in cryptococcal disease emerging or..
    • The development of fluconazole resistance in Candida albicans–an..
    • The genetic basis of fluconazole resistance development in Candida..

    Resistance to azole antifungals was reported in the late 1980s in C. albicans after prolonged therapy with miconazole and ketoconazole. Fluconazole is a. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp. including the global health threat Candida auris, are largely unknown. In order to. Cameron ML, Schnell WA, Bruch S, et al. Correlation of in vitro fungal resistance of Candida isolates in relation to therapy and symptoms of individuals.

     
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