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Antifungal therapy is an important element of patient management for acute and chronic diseases. Yet, as the global burden of fungal infections rises, treatment choices are constrained due to limited classes of antifungal agents. Furthermore, clinical management of fungal diseases is made even more tenuous by the emergence of antifungal drug resistance. More recently, the evolution of multidrug resistant organisms refractory to several different classes of antifungal agents is alarming. The resistance mechanisms responsible are largely shared by strains displaying inherently reduced susceptibility to specific antifungal agents and strains acquiring resistance during therapy. The principal molecular mechanisms are well characterized and include diminished drug-target interactions through changes in affinity and target abundance, and reduction in the intracellular level of drug through expression of high-capacity efflux pumps and biofilm formation. In some strains, high-level resistance occurs through a
Sigma-Aldrich offers abstracts and full-text articles by [Xiaoyuan He, Mingfeng Zhao, Jinyan Chen, Rimao Wu, Jianlei Zhang, Rui Cui, Yanyu Jiang, Jie Chen, Xiaoli Cao, Yi Xing, Yuchen Zhang, Juanxia Meng, Qi Deng, Tao Sui].
Summary During recent years, inappropriate antifungal use has contributed to the global increase in antifungal resistance and has played a role in the shift in ...
BioAssay record AID 1084661 submitted by ChEMBL: Antifungal activity against Candida albicans clinical isolate after 24 to 48 hr by CLSI broth microdilution method.
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Fungal biofilms were more resistant to antimicrobial agents than planktonic cells. Four distinct growth phases in relation to antifungal susceptibility were examined. Our results demonstrated that all three strains became increasingly resistant to antifungal agents throughout morphological differentiation, which was consistent with the report by Imamura et al., 10 showing that Fusarium biofilms exhibited reduced susceptibility to lens care solutions in a time-dependent manner. Moreover, our results showed that the mature biofilms were intrinsically resistant to the azole antifungal drugs (FLU, VRC, and ITC). Multiple mechanisms have been proposed for the increased resistance of biofilms to antifungal agents. Our results indicate that ECM increased and a network of hyphal structures formed throughout the incubation time. The architecture of biofilms and the presence of ECM might reduce the diffusion of antifungal drugs, and they may be responsible for the increased resistance of biofilms to ...
Theodore White, professor and dean of the School of Biological Sciences at the University of Missouri, Kansas City, will present "The Ins and Outs of Antifungal Drug Resistance" as part of the Division of Biology Seminar Series at 4 p.m. Friday, Oct. 14, in 221 Ackert Hall.. Whites lecture will provide a cross section of issues that contribute to antifungal drug resistance in pathogenic fungi. White will discuss the basic mechanisms, the transcriptional regulators and generalized mechanisms across funal species. He will present current understanding of how a series of 17 clinical isolates developed high level resistance. White also will discuss his recent work on how Azole antifungals are imported into cells, and genes in the ergosterol pathway and their contributions to antifungal resistance and to the responses to other environmental stressors.. ...
The treatment of fungal plant pathogens through the use of fungicide applications is and will remain essential for maintaining healthy crops and reliable high-quality yields therefore understanding fungicide resistance is paramount.
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This chapter critically evaluates some common assumptions regarding antifungal resistance and highlights key clinical problems that arise when managing patients with invasive infections caused by antifungal-resistant Candida species. Although this paper gives perhaps the first example of in vivo-acquired mutations in a fungal gene with a positive impact on in vivo fitness, all of the clinical isolates used in the study were acquired from semi-invasive infections of the oropharynx rather than the bloodstream of patients. The majority of patients with invasive mycoses probably fail therapy because of underlying host factors, rather than acquired resistance to the drug. One of the most underappreciated causes of treatment failures in Candida species is biofilm-mediated resistance. Problems associated with timely diagnosis and early detection of antifungal resistance in Candida species have not improved over the last two decades, as current testing approaches still rely primarily on blood cultures, which
(PhysOrg.com) -- A team of scientists from the Netherlands, including Gert Kema of Plant Research International, published an article in the Lancet Infectious Diseases about the relationship between fungicide use in agriculture ...
Other. The Systemic Oral Azoles report does the thorough study of the key industry players to understand their business strategies, annual revenue, company profile and their contribution to the Systemic Oral Azoles market share in the United States. Diverse factors of the Systemic Oral Azoles industry like the supply chain scenario, industry standards, import/export details are also mentioned in this report.. Key Highlights of the United States Systemic Oral Azoles Market 2017 Report:. A Clear understanding of the Systemic Oral Azoles market based on growth, constraints, opportunities, feasibility study.. Concise Systemic Oral Azoles Market study based on major United States regions.. Analysis of evolving market segments as well as a complete study of existing Systemic Oral Azoles market segments.. Before Purchasing, Request Free Sample Copy of the Report Here: http://qyresearch.us/report/united-states-systemic-oral-azoles-market-2017/100864/#requestForSample. Furthermore, distinct aspects of ...
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A need to revisit clinical breakpoints of tigecycline: effect of atypical non-linear plasma protein binding. Author information: Singh RS1, Mukker JK1, Drescher SK1, Deitchman AN1, Derendorf ...
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Background: Azoles and polyenes are antifungal agents used for treatment and/or prophylaxis of C. albicans infections, and a high increase in antifungal resistance in clinical isolates of C. albicans in HIV/AIDS patients has been reported. Five genetic clades were described among C. albicans isolates using DNA fingerprinting methods (clades I, II, III, SA and NG). Although these clades have been described, little is known about their phenotypic characteristics, and not much is known about antifungal resistance with regard to each of these clades. The widespread use of fluconazole has led to its increased resistance reported world-wide. Resistance to fluconazole can be caused by point mutations in the ERG11 gene or overexpression of this gene, however, not much is known about the contribution of these mutations and over-expression to fluconazole resistance among different clades of C. albicans, and whether mutations or over-expression are clade-related. There is evidence to suggest that ...
article{5cf566a8-21ef-4c37-927c-b4548bf4fe7f, abstract = {Objectives: The aim of this study was to establish wild-type MIC distributions of first-line drugs for Mycobacterium tuberculosis, as well as to explore the usefulness of such distributions when setting clinical breakpoints. Methods: We determined the MICs of rifampicin, isonlazid and ethambutol for M. tuberculosis using a Middlebrook 7H10 dilution method for 90 consecutive clinical isolates, 8 resistant strains and 16 isolates from the WHO proficiency test panel. M. tuberculosis H37Rv was used for quality control and susceptibility results using 7H10 were compared with the results obtained with BACTEC460. Results: The agreement with BACTEC460 was very high for isonlazid (99.1%) and rifampicin (99.1%) but lower for ethambutol (94.7%). Intra- and inter-assay variation was below one MIC dilution. The MIC distributions for isoniazid and rifampicin provided a clear separation between susceptible and resistant strains. Regarding ethambutol, ...
The widespread application of antifungal drugs such promotes selection of resistant organisms by either inducing resistant subspecies of normally susceptible organisms or shifting colonization to more intrinsically resistant species.
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New life-saving treatments for Invasive pulmonary | aspergillosis in clinical trial on PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome.
The aims of the present study are to investigate the prevalence and the epidemiology of candidaemia and to determine the antifungal susceptibility patterns of Candida spp. isolates from a tertiary-care hospital in Italy ...
Fumigatus isolates from India harboring TR34/ L98H mutations in the cyp51A gene, from soil samples of paddy fields, tea gardens, cotton trees, flower pots and
Antifungals are drugs that are used to treat fungal infections. Like antibiotics, antifungals stop the germ (in this case a fungus) from functioning normally. But there are not as many different groups of antifungals as there are antibiotics, and it is only fairly recently that effective antifungals have been developed. ...
Martin Sewell is a Family Lawyer specialising in Child Protection and Adoption and an Anglican Lay Reader. His work puts him in daily contact with the disadvantaged of society who experience the consequences of social policy the most acutely. In...
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Thiabendazole, an antifungal in clinical use for 40 years, inhibits angiogenesis, slows growth, and reduces vascular density of tumors.
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Candida glabrata is a major opportunistic human fungal pathogen causing superficial as well as systemic infections in immunocompromised individuals and several other patient cohorts. C. glabrata represents the second most prevalent cause of candidemia and a better understanding of its virulence and drug resistance mechanisms is thus of high medical relevance. In contrast to the diploid dimorphic pathogen C. albicans, whose ability to undergo filamentation is considered a major virulence trait, C. glabrata has a haploid genome and lacks the ability to switch to filamentous growth. A major impediment for the clinical therapy of C. glabrata infections is its high intrinsic resistance to several antifungal drugs, especially azoles. Further, the development of antifungal resistance, particularly during prolonged and prophylactic therapies is diminishing efficacies of therapeutic interventions. In addition, C. glabrata harbors a large repertoire of adhesins involved in the adherence to host epithelia.
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Literature Cited. 1. Black, L. L., McInnes, T. B., and Gatti, J. M. 1990. Evaluation of fungicides for control of strawberry fruit rots in Louisiana. Adv. Strawberry Prod. 9:33-36.. 2. Braun, P. G., and Sutton, J. C. 1987. Inoculum sources of Botrytis cinerea in fruit rot of strawberries in Ontario. Can. J. Plant Pathol. 9:1-5.. 3. Brent, K. J., and Hollomon, D. W. 2007. Fungicide resistance in crop pathogens: How can it be managed? FRAC Monagraph No. 1, 2nd Edn. Fungicide Resistance Action Committee, CropLife International A.I.S.B.L., Brussels, Belgium.. 4. Bristow, P. R., McNicol, R. J., and Williamson, B. 1986. Infection of strawberry flowers by Botrytis cinerea and its relevance to grey mould development. Ann. Appl. Biol. 109:545-554.. 5. Bulger, M. A., Ellis, M. A., and Madden, L. V. 1987. Influence of temperature and wetness duration on infection of strawberry flowers by Botrytis cinerea and disease incidence of fruit originating from infected flowers. Phytopathology 77:1225-1230.. 6. ...
While azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. Infections involving azole resistant forms of the filamentous fungus Aspergillus fumigatus are often associated with genetic changes in the cyp51A gene encoding the lanosterol α14 demethylase target enzyme. Both a sequence duplication in the cyp51A promoter (TR34) as well as a substitution mutation in the coding sequence (L98H) are required for full expression of azole resistance. A mechanism commonly observed in pathogenic yeast such as Candida albicans involves gain-of-function mutations in transcriptional regulatory proteins that induce expression of ATP-binding cassette (ABC) transporter encoding genes. We and others have found that an ABC transporter protein called Cdr1B (here referred to as AbcG1) is required for wild-type azole resistance in A.fumigatus Here we test the genetic relationship between the TR34 L98H allele of ...
Increased fluconazole resistance has been noted in oral C. albicans isolates from patients with very advanced AIDS who have been receiving fluconazole over long periods. Both the acquisition of new strains and increased resistance in prior strains have been noted (4, 6, 14). Multiple mechanisms of resistance have been reported, including mutations in the gene coding for the azole target enzyme, C14 sterol demethylase, and increased transcription of multidrug efflux transporters (19, 21). As in the case for AIDS, one of us has previously identified two transplant recipients whose C. albicans isolates became resistant to fluconazole and who developed deep infections (11, 12). The isolates for these patients exhibited increased expression of efflux pumps (12). Isolates from one of these patients developed drug resistance in a little over 2 weeks, similar to the findings reported here for C. glabrata, for which the MIC doubled an average of every 31 days. Although we did not attempt to assess the ...
The genetic heterogeneity and antifungal susceptibility patterns of Candida parapsilosis isolated from blood cultures of patients were investigated in this study. Randomly amplified polymorphic DNA (RAPD) analysis generated 5 unique profiles from 42 isolates. Based on the major DNA fragments of the RAPD profiles, the isolates were identified as RAPD type P1 (29 isolates), P2 (6 isolates), P3 (4 isolates), P4 (2 isolates) and P5 (1 isolate). Sequence analysis of the internal transcribed spacer (ITS) gene of the isolates identified RAPD type P1 as C. parapsilosis, P2 and P3 as Candida orthopsilosis, P4 as Candida metapsilosis, and P5 as Lodderomyces elongisporus. Nucleotide variations in ITS gene sequences of C. orthopsilosis and C. metapsilosis were detected. Antifungal susceptibility testing using Etests showed that all isolates tested in this study were susceptible to amphotericin B, fluconazole, ketoconazole, itraconazole and voriconazole. C. parapsilosis isolates exhibited higher MIC50 values than
Susceptibilities to antifungal drugs of 1083 Candida isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 2010 were determined. There were 422 (39%) C albicans, 270 (24.9%) C tropicalis, 258 (23.8%) C glabrata, 87 (8%) C. parapsilosis, 18 (1.7%) C. krusei, and 28 (2.6%) of 13 other species. In the present study, we have applied species-specific clinical breakpoints for common species and epidemiological cutoff values for rare species. We found that majority of isolates were susceptible to tested drugs. A total of 15, 3, 2, and 0 isolates were not susceptible to fluconazole, voriconazole, amphotericin B, and anidulafungin, respectively. We found that three of the four fluconazole non-susceptible C albicans isolates were resistant to voriconazole. Hence, there is an issue of cross-resistance among azole-type drugs. (C) 2013 Elsevier Inc. All rights reserved.
C. dubliniensis is now well recognized as a significant human pathogen and is primarily associated with oral carriage and infection in HIV-infected individuals. Previous studies have shown that stable resistance to fluconazole can readily be induced in vitro in this species (10, 30, 31). Moreover, fluconazole-resistant C. dubliniensis isolates have been recovered from HIV-infected and AIDS patients treated with fluconazole for prolonged periods of time and have been shown to replace susceptible strains (36, 41). Recently, Perea and colleagues (36) showed that, as is the case in C. albicans, resistance to fluconazole in C. dubliniensis clinical isolates was associated with combinations of different molecular mechanisms such as upregulation of the multidrug resistance genes CdCDR1 and CdMDR1, upregulation of CdERG11, and the presence of mutations in CdErg11p. In C. albicans, almost all isolates with reduced susceptibilities to azoles analyzed to date exhibit increased levels of CDR1 expression ...
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A main characteristic associated with microbial biofilms is their increased resistance to antimicrobial chemotherapies. However, at present very little is known about the phenotypic changes that occur during the transition from the planktonic to the biofilm mode of growth. Candida albicans biofilms …
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The polymorphic yeast Candida albicans, recently highlighted in the Microbe Profiles section of Microbiology, is the most important fungal pathogen in humans. Beyond the clinics, basic research in this organism deals with a variety of topics of interest, like the Genetics and Molecular Biology behind antifungal drug resistance; the molecular determinants of endurance to nutritional, pH and oxidative stress imposed by the host defenses; or its interactions with both the host epithelia and bacterial partners that share the mucosal microbiota with the fungus ...
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BioAssay record AID 518980 submitted by ChEMBL: Increase in slt2 gene expression in Candida glabrata 200989 at 0.125 to 16 ug/ml after 10 mins by RT-PCR analysis relative to control.