Drug Resistance, Fungal
A genus of yeast-like mitosporic Saccharomycetales fungi characterized by producing yeast cells, mycelia, pseudomycelia, and blastophores. It is commonly part of the normal flora of the skin, mouth, intestinal tract, and vagina, but can cause a variety of infections, including CANDIDIASIS; ONYCHOMYCOSIS; vulvovaginal candidiasis (CANDIDIASIS, VULVOVAGINAL), and thrush (see CANDIDIASIS, ORAL). (From Dorland, 28th ed)
Microbial Sensitivity Tests
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
14-alpha Demethylase Inhibitors
Cyclic hexapeptides of proline-ornithine-threonine-proline-threonine-serine. The cyclization with a single non-peptide bond can lead them to be incorrectly called DEPSIPEPTIDES, but the echinocandins lack ester links. Antifungal activity is via inhibition of 1,3-beta-glucan synthase production of BETA-GLUCANS.
Drug Resistance, Microbial
Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains. (1/584)We investigated the effects of combining tacrolimus and azole antifungal agents in azole-resistant strains of Candida albicans by comparing the accumulation of [3H]itraconazole. The CDR1-expressing resistant strain C26 accumulated less itraconazole than the CaMDR-expressing resistant strain C40 or the azole-sensitive strain B2630. A CDR1-expressing Saccharomyces cerevisiae mutant, DSY415, showed a marked reduction in the accumulation of both fluconazole and itraconazole. A CaMDR-expressing S. cerevisiae mutant, DSY416, also showed lower accumulation of fluconazole, but not of itraconazole. The addition of sodium azide, an electron-transport chain inhibitor, increased the intracellular accumulation of itraconazole only in the C26 strain, and not in the C40 or B2630 strains. Addition of tacrolimus, an inhibitor of multidrug resistance proteins, resulted in the highest increase in itraconazole accumulation in the C26 strain. The combination of itraconazole and tacrolimus was synergic in azole-resistant C. albicans strains. In the C26 strain, the MIC of itraconazole decreased from >8 to 0.5 mg/L when combined with tacrolimus. Our results showed that two multidrug resistance phenotypes (encoded by the CDR1 and CaMDR genes) in C. albicans have different substrate specificity for azole antifungal agents and that a combination of tacrolimus and azole antifungal agents is effective against azole-resistant strains of C. albicans. (+info)
Protection of ebselen against anoxic damage of cultured neurons of cerebral cortex. (2/584)AIM: To study the protective effect of ebselen on anoxic damage of brain cells. METHODS: On d 10 after plating of the cortical neurons from 1-d-old rat, cultures were placed under 95% N2 + 5% CO2 for 2-6 h. Lactate dehydrogenase (LDH) in supernatant, thiobarbituric acid reactive substance (TBARS) and glutathione peroxidase (GSH-Px) activity of neurons were determined. RESULTS: Under anoxia, efflux of LDH and TBARS from cultured neurons increased while GSH-Px activity decreased. Ebselen reduced the efflux of LDH and TBARS in a dose-related manner and increased the total GSH-Px activity. CONCLUSION: Ebselen can protect neurons from anoxic damage. (+info)
Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans. (3/584)Oral infections caused by the yeast Candida albicans are some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. In C. albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination of Candida in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance. 35S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition. (+info)
Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450. (4/584)The sterol 14-demethylase P450 (CYP51) of a fluconazole-resistant isolate of Candida albicans, DUMC136, showed reduced susceptibility to this azole but with little change in its catalytic activity. Twelve nucleotide substitutions, resulting in four amino acid changes, were identified in the DUMC136 CYP51 gene in comparison with a reported CYP51 sequence from a wild-type, fluconazole-susceptible C. albicans strain. Seven of these substitutions, including all of those causing amino acid changes, were located within a region covering one of the putative substrate recognition sites of the enzyme (SRS-1). Polymorphisms within this region were observed in several C. albicans isolates, and some were found to be CYP51 heterozygotes. Among the amino acid changes occurring in this region, only an alteration of Y132 was common among these fluconazole-resistant isolates, which suggests the importance of this residue to the fluconazole resistance of the target enzyme. DUMC136 and another fluconazole-resistant isolate were homozygotes with respect to CYP51, although the typical wild-type, fluconazole-susceptible C. albicans was a CYP51 heterozygote. These findings suggest that part of the fluconazole-resistant phenotype of C. albicans DUMC136 was acquired through a mutation-prone area of CYP51, an area which might promote the formation of fluconazole-resistant CYP51, along with a mechanism(s) which allows the formation of a homozygote of this altered CYP51 in this diploid pathogenic yeast. (+info)
When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid. (5/584)The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with alpha-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of alpha-tocopherol was not a prerequisite for unmasking the pro-oxidant activity of uric acid, since this became apparent even when alpha-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous alpha-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions. (+info)
Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51. (6/584)CYP51s form the only family of P450 proteins conserved in evolution from prokaryotes to fungi, plants and mammals. In all eukaryotes, CYP51s catalyse 14alpha-demethylation of sterols. We have recently isolated two CYP51 cDNAs from sorghum [Bak, S., Kahn, R.A., Olsen, C. E. & Halkier, B.A. (1997) Plant J. 11, 191-201] and wheat [Cabello-Hurtado, F., Zimmerlin, A., Rahier, A., Taton, M., DeRose, R., Nedelkina, S., Batard, Y., Durst, F., Pallett, K.E. & Werck-Reichhart, D. (1997) Biophys. Biochem. Res. Commun. 230, 381-385]. Wheat and sorghum CYP51 proteins show a high identity (92%) compared with their identity with their fungal and mammalian orthologues (32-39%). Data obtained with plant microsomes have previously suggested that differences in primary sequences reflect differences in sterol pathways and CYP51 substrate specificities between animals, fungi and plants. To investigate more thoroughly the properties of the plant CYP51, the wheat enzyme was expressed in yeast strains overexpressing different P450 reductases as a fusion with either yeast or plant (sorghum) membrane targeting sequences. The endogenous sterol demethylase gene (ERG11) was then disrupted. A sorghum-wheat fusion protein expressed with the Arabidopsis thaliana reductase ATR1 showed the highest level of expression and activity. The expression induced a marked proliferation of microsomal membranes so as to obtain 70 nmol P450.(L culture)-1, with CYP51 representing 1.5% of microsomal protein. Without disruption of the ERG11 gene, the expression level was fivefold reduced. CYP51 from wheat complemented the ERG11 disruption, as the modified yeasts did not need supplementation with exogenous ergosterol and grew normally under aerobic conditions. The fusion plant enzyme catalysed 14alpha-demethylation of obtusifoliol very actively (Km,app = 197 microm, kcat = 1.2 min-1) and with very strict substrate specificity. No metabolism of lanosterol and eburicol, the substrates of the fungal and mammalian CYP51s, nor metabolism of herbicides and fatty acids was detected in the recombinant yeast microsomes. Surprisingly lanosterol (Ks = 2.2 microM) and eburicol (Ks = 2.5 microm) were found to bind the active site of the plant enzyme with affinities higher than that for obtusifoliol (Ks = 289 microM), giving typical type-I spectra. The amplitudes of these spectra, however, suggested that lanosterol and eburicol were less favourably positioned to be metabolized than obtusifoliol. The recombinant enzyme was also used to test the relative binding constants of two azole compounds, LAB170250F and gamma-ketotriazole, which were previously reported to be potent inhibitors of the plant enzyme. The Ks of plant CYP51 for LAB170250F (0.29 microM) and gamma-ketotriazole (0.40 microM) calculated from the type-II sp2 nitrogen-binding spectra were in better agreement with their reported effects as plant CYP51 inhibitors than values previously determined with plant microsomes. This optimized expression system thus provides an excellent tool for detailed enzymological and mechanistic studies, and for improving the selectivity of inhibitory molecules. (+info)
Comparison of the toxicity of fluconazole and other azole antifungal drugs to murine and human granulocyte-macrophage progenitor cells in vitro. (7/584)We studied the inhibitory effects on colony formation by granulocyte-macrophage colony forming units (cfu-gm) of eight azole antifungal agents in vitro. All agents, except fluconazole, inhibited colony formation dose-dependently with 50% inhibitory concentrations (IC50) in the range of 0.78-49 micromol/L in cultures of murine and human bone marrow. For human cells, the IC50 values were 0.553 mg/L for itraconazole, 1.24 mg/L for saperconazole, 2.58 mg/L for clotrimazole, 5.33 mg/L for miconazole, 6.17 mg/L for econazole, 6.27 mg/L for ketoconazole and 8.38 mg/L for oxiconazole. The IC50 of itraconazole for human cfu-gm in vitro was similar to the plasma level of this drug recommended for systemic antifungal therapy (>0.5 mg/L) thus indicating the potential clinical relevance of our data. The IC50 of ketoconazole for human cfu-gm in vitro may be exceeded by plasma levels produced in vivo by high (> or =400 mg) doses, whereas fluconazole failed to reduce colony formation by 50% even at 100 mg/L, a concentration not reached in vivo even after extremely high doses (2000 mg/day). To most of the drugs studied, murine progenitor cells seemed to be less sensitive than the human ones. There was, however, a close correlation between the murine and human log IC50 values of the drugs (r2 = 0.964, P< 0.001), suggesting that cultures of murine bone marrow may be suitable to predict the in-vitro toxicity of azole antifungals to human cfu-gm. (+info)
The inhibition of mammalian 15-lipoxygenases by the anti-inflammatory drug ebselen: dual-type mechanism involving covalent linkage and alteration of the iron ligand sphere. (8/584)Mammalian lipoxygenases have been implicated in inflammation and atherosclerosis and, thus, lipoxygenase inhibitors may be of pharmacological interest. In cells, lipoxygenases occur in a catalytically silent ground state that requires activation to become active. We found that the seleno-organic drug ebselen [2-phenyl-1, 2-benzisoselenazol-3(2H)-one], which exhibits anti-inflammatory properties, irreversibly inhibited pure rabbit 15-lipoxygenase, with an IC50 in the nM range when preincubated with the enzyme in the absence of fatty acid substrates. Subsequent dialysis, gel filtration, or substrate addition did not restore the enzyme activity, and experiments with [14C]ebselen indicated a covalent linkage of the drug. The presence of sulfhydryl compounds in the incubation mixture prevented both enzyme labeling and inactivation, but we did not see any reactivation when sulfhydryl compounds were added afterward. X-ray absorption studies indicated that ebselen did alter the geometry of the iron ligand sphere, and the data are consistent with an iron complexation by the drug. When fatty acid substrate was present during lipoxygenase-ebselen interaction, the inhibitory potency was strongly reduced and a competitive mode of action was observed. These data suggest that ebselen inactivated the catalytically silent ground-state lipoxygenase irreversibly by covalent linkage and alteration of the iron ligand sphere. In contrast, it functions as a competitive inhibitor of the catalytically active enzyme species. The pharmacological relevance of ebselen as a potential in vivo lipoxygenase inhibitor will be discussed. (+info)
Characteristics of azole-resistant Aspergillus fumigatus attached to agricultural products imported to Japan. - Fungal...
Due to the increase in the number of azole-resistant Aspergillus fumigatus, there is an urgent need of data to predict future trends and prevent further spreading. The intercountry transfer of resistant A. fumigatus on plant bulbs have been reported. We investigated existence and characteristics of resistant isolates attached to agricultural products imported to Japan. We purchased 292 samples in Japan. All samples were screened for the existence of azole-resistant A. fumigatus. For positive isolates, minimum inhibitory concentrations of the drugs were determined. We also analyzed Cyp51A, Hmg1, and Erg6 mutations of these isolates and conducted microsatellite genotyping. Fourteen azole-resistant isolates were detected, of which 13 were cultured from flower bulbs imported from the Netherlands. Among them 5 were from 11 bulbs of Hippeastrum (45.5%), 5 were from 24 bulbs of Gladiolus (20.8%), 2 were from 4 bulbs of Ixia (50.0%), and 1 was from 22 bulbs of Tulipa (4.5%). Only 1 resistant isolate was ...
Detection of TR 34 /L98H CYP51A Mutation through Passive Surveillance for Azole-Resistant Aspergillus fumigatus in the United...
The emergence of azole-resistant Aspergillus fumigatus has become a clinical problem in many parts of the world. Several amino acid mutations in the azole target protein Cyp51Ap contribute to this resistance, with the most concerning being the environmentally derived TR34 /L98H and TR46 /Y121F/T289A mutations. Here, we performed passive surveillance to assess a sample of the A. fumigatus population in the United States for the presence of these mutations. We found 1.4% of those isolates to exhibit elevated MIC via broth microdilution, and five of those isolates harbored the TR34 /L98H mutation ...
Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14α-Demethylase (CYP51A1) from Azole-Resistant Candida albicans...
Resistance to azole antifungal agents has been shown to be attributable to a variety of mechanisms (12, 37, 38). Only recently have approaches aimed to reveal these mechanisms at the molecular level been undertaken. In a group of C. albicans isolates from AIDS patients that we investigated, we observed that azole antifungal agents failed to accumulate to the levels measured in azole-susceptible isolates (30). The cause of this effect was linked to the enhanced expression of efflux multidrug transporters genes, namely CDR1, CDR2, and BENr (28, 30). The overexpression of the ATP binding cassette transporter genes CDR1 andCDR2 is capable of mediating cross-resistance to known azole derivatives, including fluconazole, ketoconazole, and itraconazole (28, 30). The overexpression of the major facilitator geneBENr is linked only with the acquisition of resistance to fluconazole (1, 28, 30). Of the azole-resistant isolates investigated in this study, only one (C40) overexpressed the BENr gene without a ...
AID 322857 - Antifungal activity against azole-resistant Aspergillus fumigatus V34/75-CM3276 isolate from patient with hyper...
BioAssay record AID 322857 submitted by ChEMBL: Antifungal activity against azole-resistant Aspergillus fumigatus V34/75-CM3276 isolate from patient with hyper-immunoglobulin E syndrome by broth microdilution susceptibility test.
United States Systemic Oral Azoles Market 2017- Novartis AG, Pfizer, Inc, Sanofi-Aventis - Herald Analyst
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 ...
Azole Antifungal Drugs: Old and New | Annals of Internal Medicine | American College of Physicians
The therapeutic armamentarium against both systemic and superficial fungal infections consists primarily of the polyenes, amphotericin B and nystatin; flucytosine, a fluorinated pyrimidine analogue; and the older antifungal azoles, clotrimazole, miconazole, and ketoconazole. Results of recent studies give promise that new investigational antifungal oral azole drugs, including itraconazole, fluconazole, and SCH 39304, will be exciting additions to current compounds. Although none of these new azoles has been approved by the Food and Drug Administration yet, two of them, itraconazole and fluconazole, have already been extensively studied in in-vitro and in-vivo animal model systems, and to a lesser degree in humans. ...
A Novel Environmental Azole Resistance Mutation in Aspergillus fumigatus and a Possible Role of Sexual Reproduction in Its...
This study investigated the dynamics of Aspergillus fumigatus azole-resistant phenotypes in two compost heaps with contrasting azole exposures: azole free and azole exposed. After heat shock, to which sexual but not asexual spores are highly resistant, the azole-free compost yielded 98% (49/50) wild-type and 2% (1/50) azole-resistant isolates, whereas the azole-containing compost yielded 9% (4/45) wild-type and 91% (41/45) resistant isolates. From the latter compost, 80% (36/45) of the isolates contained the TR46/Y121F/T289A genotype, 2% (1/45) harbored the TR46/Y121F/M172I/T289A/G448S genotype, and 9% (4/45) had a novel pan-triazole-resistant mutation (TR463/Y121F/M172I/T289A/G448S) with a triple 46-bp promoter repeat. Subsequent screening of a representative set of clinical A. fumigatus isolates showed that the novel TR463 mutant was already present in samples from three Dutch medical centers collected since 2012. Furthermore, a second new resistance mutation was found in this set that ...
Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates
TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be …
Azole antifungal comparison - Glucotrol side effects
systems, such as azole antifungals and macrolide. comparison was between E20 and L10 groups; if this was significant, then comparisons of E10 to L10 groups.Determination of the Chemical Composition and Antioxidant Activity of the Essential Oil of Artemisia dracunculusand of the Antifungal and Antibacterial Activities of.However, in comparison with the controls, the chitosan. Antifungal activity of chitosan in Cladosporium cladosporioides isolated from safflower.Comparison of biofilms formed by Candida albicans and Candida. R. Danesi, M. Campa, M. Del Tacca, S. Kelly, 2002. Molecular basis of resistance to azole antifungals.. azole antifungals, such as itraconazole and flucona- zole, have a better safety profile. Another antifungal agent is terbinafine, an ally- lamine. 7.NF- Bsignalingpathwaysinmammalian andinsectinnateimmunity. the Toll/antifungal pathway leads to the activation of. Comparison of the Drosophila and mammalian innate.Canadian by diflucan - buy canada in propecia Low Price ...
The Qsar Study of Azole Derivatives Using Molecular Descriptors for Quantum Molecular States
Azoles are the main antifungal agents currently used in systemic therapy and local mycoses. The class of azole derivatives has been studied using fingerprint descriptors based on electronegativity of the occupied molecular orbitals (OMO) and unoccupied molecular orbitals (UMO). The Hansch equations that correlates partition coefficient with chemical structure allows us to identify the nature of the atoms involved in ligand (drug) - receptor interactions, as well as the nature of those interactions. The results indicate that in the most reactive molecular states, such as states HOMO and LUMO, the oxygen atoms are actually involved in the interaction of the ligand - receptor by the transfer of electrons from the biological receptor to the oxygen atoms.
Azole Antifungals Drug Class Overview, Drugs, Side Effects, and Interactions. Get free Azole Antifungals Drug Coupon and Discount at Save.Health
Azole Antifungals Drug Class Overview, Drugs, Side Effects, and Interactions. Get free Azole Antifungals Drug Coupon and Discount at Rebates.com
Emergence of Azole Resistance in Aspergillus<...
TY - JOUR. T1 - Emergence of Azole Resistance in Aspergillus. AU - Wiederhold, Nathan. AU - Patterson, Thomas F. PY - 2015/10/25. Y1 - 2015/10/25. N2 - Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. Some resistant isolates also contain a tandem repeat in the promoter region of this gene that causes increased expression. These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated ...
Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus
To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previo …
azole resistance mechanisms in clinical isolates of Candida albicans and Cryptococcus neoformans from intensive care patients |...
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PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome. | Clinical Research Trial Listing (...
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.
Azole-resistant Aspergillus and Echinocandin-resistant Candida - What are the treatment options? - Infectoforum
Summary: When either ERC or ARAF are suspected or proven, amphotericin products remain the cornerstone of initial therapy. For ERC, azoles are de-escalation options for susceptible isolates in stable patients to avoid amphotericin toxicities. Although combination echinocandin with high-dose salvage posaconazole or isavuconazole may be attempted in ARAF, it requires careful consideration following patient stabilization. Future research defining optimal therapies and early identification of ERC and ARAF is of extreme importance ...
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In recent years acquired azole resistance in Aspergillus fumigatus has been increasingly reported and a dominant mechanism of resistance (TR34/L98H) was found in clinical and environmental isolates. The aim of the present study was to investigate the prevalence of azole resistance in environmental A. fumigatus isolates collected in northern Italy. A. fumigatus grew from 29 of 47 soil samples analysed. Azole-resistant isolates were detected in 13% (6/47) of the soil samples and in 21% (6/29) of the soil samples containing A. fumigatus. High minimal inhibitory concentrations (MIC) of itraconazole (≥16 mg/L) and posaconazole (≥0.5 mg/L) were displayed by nine isolates from six different soil samples, namely apple orchard (1 sample), rose pot compost (2 samples), and cucurbit yields (3 samples). Seven isolates had a MIC=2 mg/L of voriconazole. Seven of nine itraconazole and posaconazole resistant isolates harboured the same TR34/L98H mutation of cyp51A. These findings, together with the occurrence of
Biochemical targets for antifungal azole derivatives: hypothesis on the mode of action. - PubMed - NCBI
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United States Systemic Oral Azoles Market Report 2017 : ReportsnReports
[104 Pages Report] Check for Discount on United States Systemic Oral Azoles Market Report 2017 report by QYResearch Group. In this report, the United States Systemic Oral Azoles market...
Fisher Lab - Breathe
The Evolution of Resistance. Is the widespread use of azole antifungal sprays in agricultural crops leading to environmental selection for resistance in Aspergillus fumigatus, thus resulting in decreased patient survival following infection?. A. fumigatus is a globally ubiquitous fungus, being present on decaying vegetation and in soils, where it performs a valuable role in nutrient recycling. The fungus is a minimal health threat to healthy individuals. However, patients who suffer from cystic fibrosis, cancer or who have received organ transplants and are undergoing corticosteroid therapy are at risk from invasive aspergillosis. Current estimates indicate that over 63,000 patients develop this fungal disease annually across Europe. The current method for controlling infections is by administering azole antifungal drugs, which are also used as fungicides to control crop diseases. However, we and others have shown a sharp increase in the resistance of A. fumigatus to frontline azole ...
Antihistamines and Azoles - Other antihistamines : Medicament, preparation prescriptions, order, dose, side effects
Antihistamines and Azoles - Other antihistamines : Medicaments, preparation prescriptions, order, dose, side effects, information, notice, pharma
Dr Eveline Snelders - Mycology 2020
Eveline Snelders is currently working as a post-doctoral researcher at Wageningen University & Research in The Netherlands. After investigating the clinical epidemiology and mechanisms of azole resistance in A. fumigatus during her PhD, she is now focussing on the ecological aspects and evolutionary genetics that lead to azole resistance in patients as well as in the environment.. ...
Resistance Mechanisms in Clinical Isolates of Candida albicans | Antimicrobial Agents and Chemotherapy
The goal of the series of experiments described here was to use standard techniques to identify molecular mechanisms of resistance in a collection of arbitrarily selected susceptible and resistant isolates. The results of the study do not define any specific correlations. Six strains overexpressed CDR1 and CDR2. This is much lower than the frequencies observed in oral isolates from patients with AIDS. Five of the six strains overexpressing CDR1 and CDR2 were resistant to one or more of the four azoles tested (Table 1), although the results are not statistically significant for any drug. The one strain that overexpressed MDR1 was resistant to only one azole, while low-level expression of MDR1 occurred in two strains resistant to three or four azoles (Fig. 1). Similarly, overexpression of FLU1, overexpression of ERG11, or frequent mutations within the ERG11 genes were not correlated with resistance in this collection. Overall, this suggests that standard molecular analyses of unmatched isolates is ...
Azoles as Potent Antimicrobial Agents | IntechOpen
Imidazole analogs have proved to be a very good source of medicinal agents. The various activities associated with these moieties include antibacterial, antifungal, anthelmintic, Anti HIV activity, anticancer, antihypertensive, analgesic, anti-inflammatory, anticonvulsant, sedative and other pharmacological activities.
Contributions of both ATP-binding cassette transporter and Cyp51A proteins are essential for azole resistance in Aspergillus...
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 ...
Frontiers | Accumulation of Azole Drugs in the Fungal Plant Pathogen Magnaporthe oryzae Is the Result of Facilitated Diffusion...
Magnaporthe oryzae is an agricultural mold that causes disease in rice, resulting in devastating crop losses. Since rice is a world-wide staple food crop, infection by M. oryzae poses a serious global food security threat.Fungicides, including azole antifungals, are used to prevent and combat M. oryzae plant infections. The target of azoles is CYP51, an enzyme localized on the endoplasmic reticulum (ER) and required for fungal ergosterol biosynthesis. However, many basic drug-pathogen interactions, such as how the azole gets past the fungal cell wall and plasma membrane, and is transported to the ER, are not understood. In addition, reduced intracellular accumulation of antifungals has consistently been observed as a drug resistance mechanism in many fungal species. Studying the basic biology of drug-pathogen interactions may elucidate uncharacterized mechanisms of drug resistance and susceptibility in M. oryzae and potentially other related fungal pathogens. We characterized intracellular accumulation
Azole antifungals review : Colospa retard
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Endocrine disrupting properties in vivo of widely used azole fungicides - DTU Orbit
The endocrine-disrupting potential of four commonly used azole fungicides, propiconazole, tebuconazole, epoxiconazole and ketoconazole, were tested in two short-term in vivo studies. Initially, the antiandrogenic effects of propiconazole and tebuconazole (50, 100 and 150 mg/kg body weight/day each) were examined in the Hershberger assay. In the second study, pregnant Wistar rats were dosed with propiconazole, tebuconazole, epoxiconazole or ketoconazole (50 mg/kg/day each) from gestational day (GD) 7 to GD 21. Caesarian sections were performed on dams at GD 21. Tebuconazole and propiconazole demonstrated no antiandrogenic effects at doses between 50 and 150 mg/kg body weight/day in the Hershberger assay. In the in utero exposure toxicity study, ketoconazole, a pharmaceutical to treat human fungal infections, decreased anogenital distance and reduced testicular testosterone levels, demonstrating a demasculinizing effect on male fetuses. Tebuconazole, epoxiconazole and ketoconazole induced a ...
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In vitro effects of promethazine on cell morphology and structure and mitochondrial activity of azole-resistant Candida...
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Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment | BMC...
The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5-
Recent Synthetic Strategies for Monocyclic Azole Nucleus and Its Role in Drug Discovery and Development | Bentham Science
Title:Recent Synthetic Strategies for Monocyclic Azole Nucleus and Its Role in Drug Discovery and Development. VOLUME: 15 ISSUE: 3. Author(s): Neha, Ashish Ranjan Dwivedi, Rakesh Kumar* and Vinod Kumar*. Affiliation:Laboratory of Organic and Medicinal Chemistry, Centre for Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151 001, Laboratory of Organic and Medicinal Chemistry, Centre for Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151 001, Laboratory of Organic Chemistry, Centre for Chemical Sciences, Central University of Punjab, Bathinda, Punjab 151001, Laboratory of Organic and Medicinal Chemistry, Centre for Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151 001. Keywords:Azole, heterocycles, pyrrole, pyrazole, imidazole, triazole, tetrazole, pentazole, synthetic strategies.. Abstract:Background: In recent years, the development and diversification of ...
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Pressure-treated wood has a long history−its been around since the second half of the 19th century. Wood has been preserved with chemicals containing various pesticides as a means to protect against such intruders as termites and decay fungi. This course will provide a background on traditional CCA-treated wood, and will introduce the next-generation preservative−copper azole. We will discover how it works, why it exists, what it protects against, available types, how it is made, where it is used, and how it differs from traditional treated wood, including its key features. At the completion of this course, you will be able to describe the pressure preservative process, explain the treated wood transition that occurred in 2003, discuss the features and uses of copper azole-treated wood, and detail the many environmental benefits of treated wood ...
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Azole resistance has appeared recently in Aspergillus fumigatus and increased dangerously in the last decade. The main resistance mechanism is a point
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Methylgene Wins Canadian Approval for Phase I Fungal Drug - Redorbit
MethylGene, a clinical stage biopharmaceutical company, has announced that Health Canada has approved the companys clinical trial application for MGCD290, a fungal Hos2 histone deacetylase inhibitor to be used in combination with azoles for the treatment of fungal infections. MethylGene expects to initiate a Phase I clinical trial in Canada in October 2008. The goal of this trial will be to assess the safety, pharmacokinetics and tolerability of the compound in healthy volunteers. MGCD290 will initially be administered orally as a single-agent and, in future planned studies, in combination with oral fluconazole, a widely used antifungal agent. In preclinical studies, MGCD290 in combination with fluconazole increased fungal sensitivity and broadened the spectrum of azole activity in vitro against human fungal pathogens, including azole-resistant clinical isolates, the company said. Donald Corcoran, president and CEO of MethylGene, said: MGCD290 is our first Hos2 histone deacetylase (HDAC) ...
Intensive fungicide use may lead to azole resistance in humans
(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 ...
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We herein describe novel amine-grafted metal organic frameworks (MOFs) as a promising alternative to natural peroxidase enzyme and their applications for a fluorescent assay of choline (Cho) and acetylcholine (ACh). Among diverse amine-functionalized MOFs, N,N,N',N'-tetramethyl-1,4-butanediamine (TMBDA)-functionalized MIL-100(Fe) (TMBDA-MIL-100(Fe)) exhibited the highest peroxidase activity by developing intense fluorescence from Amplex UltraRed (AUR) in the presence of H2O2, which was presumably due to the synergetic effect of the enhanced negative potential and precisely controlled molecular size of the grafted diamine. Based on the excellent peroxidase-like activity of TMBDA-MIL-100(Fe), choline and ACh were reliably determined down to 0.027 and 0.036 mu M, respectively. Furthermore, practical applicability of this strategy was successfully demonstrated by detecting choline and ACh in spiked samples of milk and serum, respectively. This work highlights the advantages of ...
In Vitro Activity of Caspofungin (MK-0991) against Candida alb...
In Vitro Activity of Caspofungin (MK-0991) against Candida albicans Clinical Isolates Displaying Different Mechanisms of Azole Resistance: Caspofungin inhibits
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Aspergillus fumigatus has widely evolved resistance to the most commonly used class of antifungal chemicals, the azoles. Current methods for identifying azole resistance are time-consuming and depend on specialized laboratories. There is an urgent need for rapid detection of these emerging pathogens at point-of-care to provide the appropriate treatment in the clinic... ...
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Given the likelihood that one of your patients is already taking a prescription drug, it is critical to be aware of potential interactions between medications. In addition to reviewing pertinent pharmacology principles, this author offers insights on azole antifungals, NSAIDs and a variety of other medications, and how to reduce the risk of harmful interactions.
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Fluka (Fluconazole) is an azole antifungal agent used in the treatment of vaginal yeast infections. A single dose usually stops the growth of most common types of vaginal yeast or fungus.
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Voriconazole(Vfend) generic is an azole antifungal agent, prescribed for various fungal infections. It works by slowing the growth of the fungi that cause infection.
Perspectives in Neglected Diseases: DND|i|i|/i| strategy for development of new treatments for Chagas Disease. - GOV.UK
This presentation describes the problem of Chagas disease, the limitations of existing treatments, and DNDis work in identifying lead compounds for the long term, developing combination therapy and repurposing antifungal azole drugs for the medium term, developing a new and better paediatric benznidazole firmulation for the short term, and developing a platform to strengthen clinical research. ...
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The special issue entitled Opportunities and Challenges in the Anticandidal Drug Discovery and Development of Letters in Drug Design & Discovery, consists of invited papers including research articles and reviews on recent trends in antifungal drug discovery. The articles in this special issue enlighten the current anticandidal therapeutic approaches including natural bioactive compounds, recent trends in anticandidal drug discovery using nanoparticles, and also synthetic compounds such as azoles. The increasing incidence of serious fungal infections is a well-recognized problem. Among all fungi, Candia is opportunistic pathogenic yeast which is responsible for the fourth leading cause of nosocomial infections. The treatment of fungal infections has very limited therapeutic options as compared to bacterial infections. The emergence of drug resistance, especially for the most successful antifungal class azole, is another worst situation associated with these infections. The purpose of this ...
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Names of azoles maintain the prefix upon reduction (e.g., pyrazoline, pyrazolidine). The numbering of ring atoms in azoles ... Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i ... One, and only one, lone pair of electrons from each heteroatom in the ring is part of the aromatic bonding in an azole. ... Azoles at the US National Library of Medicine Medical Subject Headings (MeSH) Nomenclature, IUPAC (CS1: long volume value, ...
The first azole compounds to replace this treatment were synthesized in the late 1960s and early 1970s and administered to ... It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable ... A review found that short-term rates for intravaginally administered azole treatments shows cure in 80% of cases in a short ... Heeres J, Hendrickx R, Van Cutsem J (April 1983). "Antimycotic azoles. 6. Synthesis and antifungal properties of terconazole, a ...
Ashley ED, Perfect JR (October 2017). "Pharmacology of azoles". In Kauffman CA (ed.). UpToDate. Waltham, MA: UpToDate. Archived ...
Argyropoulos, Nikolaos G. (1996). "1,4-Oxa/thia-2-azoles". Comprehensive Heterocyclic Chemistry II: 491-543. doi:10.1016/B978- ...
Topical antifungal drugs
Azole antifungals inhibit the enzyme that converts lanosterol into ergosterol. Common examples of azole antifungals include ... Mechanism of action Azole antifungal drugs exert their effects by inhibiting the synthesis of the sterol components of the ... Azoles are predominantly fungistatic which inhibit the growth of the fungus instead of killing the fungus. These drugs target ... Similar to azoles, allylamines disrupt the fungal cell wall synthesis through inhibition of the squalene epoxidase enzyme that ...
José Elguero Bertolini
Carbon-13 Magnetic Resonance Studies of Azoles. Tautomerism, Shift Reagents, and Solvent Effects. J. Org. Chem. 39, 357-363. ... hydrogen bonding and aromaticity in systems including numerous azoles and phosphaphenalenes. In physical chemistry he has ...
Argyropoulos NG (1996-01-01). "4.14 - 1,4-Oxa/thia-2-azoles". In Katritzky AR, Rees CW, Scriven EF (eds.). =Comprehensive ...
Examples of inducers include anticonvulsants like phenytoin, primidone, ethosuximide, phenobarbital, and carbamazepine; azole ...
2009). "Azoles as Reactive Nucleophiles with Cyclic Perfluoroalkenes". Chemistry. 15 (40): 10554-62. doi:10.1002/chem.200901508 ... and azoles. They or their derivatives are reported to have nonlinear optical activity, and be useful as lubricants, etching ...
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Studies in the azole series. Part II. The interaction of α-amino-nitriles and carbon disulphide". J. Chem. Soc.: 1598-1609. doi ... Studies in the azole series. Part XI. The interaction of α-amino-nitriles, hydrogen sulphide, and ketones". J. Chem. Soc.: 1061 ... Studies in the azole series. Part XIV. A new synthesis of purines". Journal of the Chemical Society (Resumed): 1071. doi: ... Studies in the azole series. Part XII. Some thiazolopyrimidines". Journal of the Chemical Society (Resumed): 1064. doi:10.1039/ ...
Studies in the azole series. Part XVI. Synthesis of a new analogue of penicillamine". Journal of the Chemical Society (Resumed ...
Azoles are the group of antifungals which act on the cell membrane of fungi. They inhibit the enzyme 14-alpha-sterol ... For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P- ... Examples of non-azole systemic antifungals include griseofulvin and terbinafine. A polyene is a molecule with ... Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4, causing increased concentration ...
... is an azole antifungal drug. Omonocazole is not available in the United States and Canada. In other countries, it ...
Sunderland MR, Cruickshank RH, Leighs SJ (2014). "The efficacy of antifungal azole and antiprotozoal compounds in protection of ... Drugs.com: sulconazole topical Fromtling RA (April 1988). "Overview of medically important antifungal azole derivatives". ...
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copper azole (CBA), another alternative to CCA. Abraham S. C. Chen (1994): "Evaluating ACQ as an Alternative wood Preservative ... "Weight loss studies of fastener materials corrosion in contact with timbers treated with copper azole and alkaline copper ...
Some people are allergic to azole(s). Some azole drugs have adverse side-effects. Some azole drugs may disrupt estrogen ... Kragie L, Turner SD, Patten CJ, Crespi CL, Stresser DM (August 2002). "Assessing pregnancy risks of azole antifungals using a ...
For decades it remained the only effective therapy for invasive fungal disease until the development of the azole antifungals ... Maertens JA (March 2004). "History of the development of azole derivatives". Clinical Microbiology and Infection. 10 (Suppl 1 ...
As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all ... As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14α-demethylase ( ... Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. ... Sanglard D, Ischer F, Monod M, Bille J (February 1997). "Cloning of Candida albicans genes conferring resistance to azole ...
Most clinical fungicides belong to the azole group. The typical fungal spore size is 1-40 micrometers in length. Protozoans are ...
Insufficient dosing of azoles has also led to the emergence of resistance. Observed rates of echinocandin resistance for C. ... Many C. auris isolates have been found to be resistant to one or more of the three major antifungal classes (azoles, ... Regional species distribution guides treatment recommendations since the species exhibit different susceptibilities to azole ...
Casadevall A, Kontoyiannis DP, Robert V (July 2019). "On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and ... with a common leap among the four varieties into drug-resistance possibly linked to widespread azole-type antifungal use in ...
Casadevall A, Kontoyiannis DP, Robert V (July 2019). "On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and ...
For example, sugar beet leaf blotch remains resistant to azoles years after they were no longer used for control of the disease ... For example, Botrytis cinerea is resistant to both azoles and dicarboximide fungicides. There are several routes by which ...
... is a member of a class of compounds known as azoles. In contrast to the isomeric thiazole, the two heteroatoms are ...
The thiazole ring is notable as a component of the vitamin thiamine (B1). Thiazoles are members of the azoles, heterocycles ...
Fungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in ... Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug ... Fluconazole is in the azole antifungal family of medication. It is believed to work by affecting the fungal cellular membrane. ... It differs from earlier azole antifungals (such as ketoconazole) in that its structure contains a triazole ring instead of an ...
Other studies employ spectrophotometry to quantify azole-CYP51 interactions. Coordination of azoles to the prosthetic heme ... from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents". Antimicrobial ... Prolonged use of azoles as antifungals has resulted in the emergence of drug resistance among certain fungal strains. Mutations ... Consequently, the focus of azole research is beginning to shift towards identifying new ways to circumvent this major obstacle ...
Replacing it are amine copper quat and copper azole. All wood preservatives used in the United States and Canada are registered ...
Price, Claire L; Parker, Josie E; Warrilow, Andrew GS; Kelly, Diane E; Kelly, Steven L (2015-08-01). "Azole fungicides - ...
Various antifungal drugs, such as amphotericin B and azole antifungals, utilize this information to kill pathogenic fungi. ... "Human Fungal Pathogens and Drug Resistance Against Azole Drugs". In Arora C, Sajid A, Kalia V (eds.). Drug Resistance in ...
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Azole fungicides are sometimes used to kill fungi that harm crops. These fungicides are similar to the azole antifungal ... Azole antifungals will kill most of the A. fumigatus in the body, but sometimes the fungus can become resistant to the ... Azole fungicides kill most A. fumigatus in the environment, but resistant A. fumigatus can survive and multiply. ... Some patients with chronic A. fumigatus infections take azole antifungals over a long time. ...
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Environmental Hotspots for Azole Resistance Selection of Aspergillus fumigatus, the Netherlands - Volume 25, Number 7-July 2019...
Azole Fungicide Measurements. We analyzed 41 samples for azole fungicides, of which 32 (78%) contained azole residues (Table). ... The presence of azole-resistant A. fumigatus in the absence of azole residues might be caused by azole-resistant A. fumigatus ... Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. ... A. fumigatus and azole fungicides were found in the flower bulb waste heaps in high quantities; high counts of azole-resistant ...
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Azole antifungals are potent inhibitors of cytochrome P450 mono-oxygenases and bacterial growth in mycobacteria and...
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... Cite ... Title : Azole Resistance of Aspergillus fumigatus in Immunocompromised Patients with Invasive Aspergillosis Personal Author(s ... Title : Azole Resistance of Aspergillus fumigatus in Immunocompromised Patients with Invasive Aspergillosis Personal Author(s ... Title : Multiple Fungicide-Driven Alterations in Azole-Resistant Aspergillus fumigatus, Colombia, 2015 Personal Author(s) : Le ...
Mucosal Candidiasis Medication: Azoles, Polyenes, Topical Antimicrobials
Azoles. Class Summary. Azoles are synthetic antifungals with broad-spectrum fungistatic activity against yeasts and fungi, ... Development of cross-resistance of C albicans to different azoles during treatment with a single azole derivative has been ... Compared with other azoles, it has lower toxicity while maintaining a half-life of 30 hours in patients with normal renal ... Most azoles have additional adverse effects specific to each drug, and these are listed below. Diazoles (eg, ketoconazole, ...
N-alkylation of azoles disubstituted acetamides under microwave and Mannich reaction conditions | Abstract
IMSEAR at SEARO: Oral hypoglycemics and azoles: an important drug interaction.
Establishing In Vitro-In Vivo Correlations for Aspergillus fumigatus: the Challenge of Azoles versus Echinocandins - Institut...
Susceptibility testing documented that the DK isolate was azole resistant (itraconazole and posaconazole MICs, ,4 microg/ml; ... Establishing In Vitro-In Vivo Correlations for Aspergillus fumigatus: the Challenge of Azoles versus Echinocandins Maiken ... Susceptibility testing documented that the DK isolate was azole resistant (itraconazole and posaconazole MICs, >4 microg/ml; ... the Challenge of Azoles versus Echinocandins. Antimicrobial Agents and Chemotherapy, 2008, 52 (10), pp.3504-3511. ⟨10.1128/AAC. ...
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Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.
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Detection of azole-resistant Aspergillus fumigatus in the environment from air, plant debris, compost, and soil. | PLoS One;18...
Azole fungicides are used in agriculture to control plant pathogens, and azoles are also used as a first line of treatment for ... The continued exposure of A. fumigatus to azoles in the environment has likely led to azole resistance in the clinic where ... Our goal was to develop assays for the rapid detection of pan-azole-resistant A. fumigatus directly from air, plants, compost, ... Pan-azole resistance in environmental isolates is most often associated with tandem-repeat (TR) mutations containing 34 or 46 ...
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Aspergillus fumigatus and pan-azole resistance: who should be concerned? - Fungal Diagnostic Testing | OLM Diagnostics
... the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis.. ... SUMMARY: Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with ... The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, ... These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. ...
Luliconazole Topical: MedlinePlus Drug Information
Aspergillosis Treatment & Management: Medical Care, Surgical Care, Consultations
Concomitant therapy with azole antifungals and amphotericin is controversial because the azole antifungals decrease ... Newer antifungal azoles are under study (eg, ravuconazole) and may be available for compassionate use in patients in whom other ... Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev. 2003. (3):CD001108. [ ... to the possibility of diminished effectiveness of amphotericin in any patient who has received prior treatment with an azole ...
Tinea pedis: not just the curse of the athlete - BPJ65 December 2014
Azole antifungals Topical azole antifungals are effective for the treatment of patients with tinea pedis infections, when used ... Other topical azole treatments available in New Zealand include a econazole 1% cream and solution (partly subsidised) and a ... Allylamine antifungals such as terbinafine are reported to be generally more effective than azole antifungals, e.g. miconazole ... in contrast with the azole antifungals which are fungistatic, i.e. inhibit fungal growth.14 ...
Nickel-Catalyzed C-H Arylation of Azoles with Haloarenes: Scope, Mechanism, and Applications to the Synthesis of Bioactive...
Novel Ni-based catalytic systems for the -H arylation of azoles with haloarenes have been developed (see scheme). Mechanistic ... Nickel-Catalyzed C-H Arylation of Azoles with Haloarenes: Scope, Mechanism, and Applications to the Synthesis of Bioactive ... Nickel-Catalyzed C-H Arylation of Azoles with Haloarenes: Scope, Mechanism, and Applications to the Synthesis of Bioactive ...
AntifungalsAspergillusItraconazoleKetoconazoleAspergillosisFungicidesAntifungal drugsIsolatesEmergenceAmphotericinPrevalenceResistantDerivativesExposureFluconazoleL98HFungicideClinicalSusceptibilityConsequenceDrug resistanceDrugsTopicalOralInfectionsMedicationsPatientsTreatmentsTreatmentSurveillanceHighGrowthTypeStudies
- Some patients with chronic A. fumigatus infections take azole antifungals over a long time. (cdc.gov)
- Azole antifungals will kill most of the A. fumigatus in the body, but sometimes the fungus can become resistant to the medication and multiply. (cdc.gov)
- Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals. (unisucre.edu.co)
- In addition, a C. albicans vps21/ mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. (unisucre.edu.co)
- Goodarzi, M & Freitas, MP 2009, ' On the use of PLS and N-PLS in MIA-QSAR: Azole antifungals ', Chemometrics and Intelligent Laboratory Systems , vol. 96, no. 1, pp. 59-62. (elsevier.com)
- Note extensive drug interactions for clarithromycin, fluoroquinolones, azole antifungals and rifampicin. (hse.ie)
- Minimum spanning tree comparing genotypic relatedness of clinical azole- resistant Aspergillus fumigatus isolates carrying TR34/L98H alteration in the CYP 51A gene from Iran with those reported from European countries. (cdc.gov)
- Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. (cdc.gov)
- Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. (cdc.gov)
- Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance. (cdc.gov)
- High prevalence of azole-resistant Aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole. (cdc.gov)
- Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene. (cdc.gov)
- Azole resistance is a major concern for treatment of infections with Aspergillus fumigatus . (cdc.gov)
- Stockpiles of plant waste contained the highest levels of azole-resistant A. fumigatus , and active aerobic composting reduced Aspergillus colony counts. (cdc.gov)
- We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. (pasteur.fr)
- Azole resistance surveillance in Aspergillus fumigatus: beneficial or biased? (ru.nl)
- Azole resistance is a growing concern with Aspergillus fumigatus, and may cause increased mortality in patients with azole-resistant invasive aspergillosis (IA). (ru.nl)
- Azole resistance frequencies have been based on screening of unselected A. fumigatus isolates, on the number of azole-resistant cases within a cohort of patients with a specific Aspergillus disease, or on analysis of patients within a specific risk group. (ru.nl)
- In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. (cdc.gov)
- Worldwide emergence of azole-resistant Aspergillus fumigatus since the late 2000s threatens human health ( 1 ). (cdc.gov)
- This observation is consistent with the estimated global prevalence of azole resistance in Aspergillus (3%-6%) and the predominance of environmental resistance mechanisms in azole-resistant A. fumigatus ( 1 , 5 ). (cdc.gov)
- Detection of azole-resistant Aspergillus fumigatus in the environment from air, plant debris, compost, and soil. (bvsalud.org)
- Aspergillus fumigatus and pan-azole resistance: who should be concerned? (olmdiagnostics.com)
- A recent article reported a 3.2% prevalence of Aspergillus fumigatus isolates that are resistant to azole from 3,788 isolates screened in Europe ( 2 ). (cdc.gov)
- This is a medical illustration of an azole-resistant fungus, Aspergillus fumigatus , presented in the Centers for Disease Control and Prevention (CDC) publication entitled, Antibiotic Resistance Threats in the United States, 2019 (AR Threats Report). (cdc.gov)
- 1 medical azoles (itraconazole, voriconazole, posaconazole, and isavuconazole) were defined as azole-resistant A. fumigatus and examined for resistance mechanisms, microsatellite-based phylogenetic relatedness, and growth rates following previously described methods ( 3 , 4 ). (cdc.gov)
- Azole resistance in A. fumigatus is becoming an increasing problem, especially in patients with aspergillomas and those with low levels of itraconazole. (life-worldwide.org)
- Diflucan is not allowed to people who have hypersensitivity to Fluconazole or other anti fungal azole preparations, eg clotrimazole, ketoconazole, itraconazole and other. (cialisonlinei.com)
- On the eighth day of terfenadine therapy the patient began a self-medicated course of ketoconazole (Nizoral-an azole antifungal) at 200 mg twice-a-day for vaginal candidiasis. (fda.gov)
- Of the azoles, ketoconazole is the only one that is approved by the US Food and Drug Administration (FDA) for treatment of coccidioidomycosis. (medscape.com)
- As most azole resistance is believed to develop in the environment and, as a consequence, azole-naive patients may present with azole-resistant aspergillosis, experts recommended a 10% resistance frequency threshold above which the standard treatment choice, i.e. voriconazole, should be reconsidered. (ru.nl)
- A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment. (cdc.gov)
- Azole fungicides are used in agriculture to control plant pathogens, and azoles are also used as a first line of treatment for aspergillosis . (bvsalud.org)
- The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis. (olmdiagnostics.com)
- SUMMARY: Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. (olmdiagnostics.com)
- As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. (olmdiagnostics.com)
- First-line antifungal therapy for invasive aspergillosis (IA) is voriconazole, which is challenged by the emergence of azole resistance ( 1 ). (cdc.gov)
- big problem because the azoles are the only class of drugs that we've got that we can give orally to patients with aspergillosis. (cdc.gov)
- Azole fungicides are sometimes used to kill fungi that harm crops. (cdc.gov)
- Azole fungicides kill most A. fumigatus in the environment, but resistant A. fumigatus can survive and multiply. (cdc.gov)
- It is generally accepted that resistance can develop through patient treatment (patient route) and through exposure of A. fumigatus to azole fungicides in the environment (environmental route) ( 2 - 9 ). (cdc.gov)
- Although A. fumigatus is not a phytopathogen and thus not a target for fungicide application, many azole fungicides show in vitro activity against A. fumigatus ( 12 , 13 ). (cdc.gov)
- We previously demonstrated that 5 azole fungicides from the triazole class were highly active against wild-type A. fumigatus but showed no activity against resistant isolates with TR 34 /L98H ( 12 ). (cdc.gov)
- When present at low concentrations in growth medium, azole antifungal drugs were shown to be potent inhibitors of the growth of Mycobacterium smegmatis and of Streptomyces strains, indicating that one or more of the P450s in these bacteria were viable drug targets. (hud.ac.uk)
- Microsatellite typing of 6 STR loci demonstrated identical patterns for two of the three azole-resistant isolates from Iran, but the TR34/L98H isolates from Iran did not cluster with those from the Netherlands and other European countries, indicating no close genetic relatedness. (cdc.gov)
- To delineate the influence of clinical and environmental use of azoles on resistance, we conducted a multicenter study that investigated 375 A. fumigatus sensu stricto isolates collected during August 2011-March 2018 from 297 patients at 11 hospitals in Taiwan ( Appendix Table 1, Figure 1). (cdc.gov)
- Overall, 19 isolates from 12 patients were azole-resistant A. fumigatus . (cdc.gov)
- Ten (83.3%) patients harbored azole-resistant A. fumigatus that had environmental mutations, including TR 34 /L98H (5 isolates, 5 patients), TR 34 /L98H/S297T/F495I (7 isolates, 4 patients), and TR 46 /Y121F/T289A (1 isolate) mutations. (cdc.gov)
- Pan- azole resistance in environmental isolates is most often associated with tandem-repeat (TR) mutations containing 34 or 46 nucleotides in the cyp51A gene . (bvsalud.org)
- These assays allow rapid surveillance of resistant isolates directly from environmental samples improving our identification of hotspots of azole -resistant A. fumigatus. (bvsalud.org)
- Among the 68 A. fumigatus isolates, 1 (1.5%) associated with probable IA was resistant to azoles ( 5 ). (cdc.gov)
- When focusing on patients with probable or proven IA, we did not observe an emergence of azole-resistant A. fumigatus isolates during 2006-2009 ( 3 ) and 2012-2014 in France. (cdc.gov)
- Emergence of azole drug resistance in Candida species from HIV-infected patients receiving prolonged fluconazole therapy for oral candidosis. (semanticscholar.org)
- A ribosomal DNA-based phylogeny was used to present phylogenetic relationships of yeasts pathogens and their close relatives and to show how the antifungal susceptibility patterns for amphotericin B and azole drugs correlate with the clades found. (opathy.eu)
- While the study revealed a male preponderance with both the fungal keratitis , it further brought out that polyene compounds (natamycin and amphotericin B) and azoles were active, respectively, against Fusarium spp. (hindawi.com)
- The antifungal Antifungal Azoles medications that are used include amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. (lecturio.com)
- Prevalence of azole-resistant A. fumigatus disease among patient populations at risk of IA was unavailable. (cdc.gov)
- Our goal was to develop assays for the rapid detection of pan- azole -resistant A. fumigatus directly from air , plants , compost , and soil samples. (bvsalud.org)
- These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus. (olmdiagnostics.com)
- The isolate harbored the TR 34 /L98H mutation ( 5 ), leading to a rate of IA caused by azole-resistant A. fumigatus of 0.7% (1/152) for total episodes recorded and 1% (1/99) for culture-positive episodes only. (cdc.gov)
- Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. (genericpedia.com)
- The antifungal activities of a series of azole derivatives have been modeled by using MIA (multivariate image analysis) descriptors. (elsevier.com)
- This research explores the phenol derivatives and azoles as raw materials to achieve dehydrogenation coupling through electrochemical oxidation, and the construction of C-N bonds for the synthesis of N -azolated aromatic products. (pku.edu.cn)
- The continued exposure of A. fumigatus to azoles in the environment has likely led to azole resistance in the clinic where infections result in high levels of mortality . (bvsalud.org)
- RECENT FINDINGS: Resistance may develop through either patient or environmental azole exposure. (olmdiagnostics.com)
- The experience with C. albicans in patients with HIV infection, suggests that the long-term azole drug use may be an important factor in the development of fluconazole resistance as such resistance was rare and transient in patients on intermittent short-term treatment. (semanticscholar.org)
- Resistance emerged mainly from the environment (TR 34 /L98H, TR 34 /L98H/S297T/F495I, and TR 46 /Y121F/T289A mutations) but occasionally during azole treatment. (cdc.gov)
- We investigated the presence of environmental hotspots for resistance selection in the Netherlands on the basis of the ability of A. fumigatus to grow and reproduce in the presence of azole fungicide residues. (cdc.gov)
- Taiwan is an island country in eastern Asia that is geographically separated from mainland Eurasia and has a long history of azole fungicide use. (cdc.gov)
- The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. (unisucre.edu.co)
- Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. (unisucre.edu.co)
- If the azole drugs prove to inhibit a number of important P450s in M. smegmatis and S. coelicolor, then the likelihood of drug resistance developing in these species should be minimal. (hud.ac.uk)
- The actinomycete P450s include homologues of 140α-sterol demethylases, the targets for the azole class of drugs in yeast and fungi. (hud.ac.uk)
- Azole drugs coordinated tightly to the haem iron in M. tuberculosis H37Rv P450s encoded by genes Rv0764c (the sterol demethylase CYP51) and Rv2276 (CYP121). (hud.ac.uk)
- This suggested that CYP121 may be a more realistic target enzyme for the azole drugs than CYP51, particularly in light of the fact that an S. coelicolor ΔCYP51 strain was viable and showed little difference in its sensitivity to azole drugs compared to the wild-type. (hud.ac.uk)
- This suggests that azole drug therapy may provide a novel antibiotic strategy against strains of M. tuberculosis that have already developed resistance to isoniazid and other front-line drugs. (hud.ac.uk)
- The World Health Organization (WHO) has also produced a classification guide for medicines use in breastfeeding based on the WHO list of essential drugs ( www.who.int/maternal_child_adolescent/documents/55732/en/ ). (medsafe.govt.nz)
- Topical azoles are effective. (medscape.com)
- La prise en charge thérapeutique doit être instaurée pour réduire le taux de mortalité et éviter les complications liées á ces infections. (bvsalud.org)
- Luliconazole is in a class of antifungal medications called azoles. (medlineplus.gov)
- Azole resistance of A. fumigatus warrants specific surveillance in hospitals treating immunocompromised patients. (cdc.gov)
- Des analyses régulières de la résistance aux antifongiques dans les centres médicaux sont fortement recommandées, car les résultats permettront une prise en charge plus efficace de la candidose systémique chez les patients immunodéprimés. (who.int)
- In some cases, such ineffective or symptoms recur, fungi, including blastomycosis, a rash has given way home treatments to relieve of an azole Practical and sneezing, and respiratory. (techhunt2025.com)
- Micronized copper azole (MCA) is a lumber treatment improve longevity. (cdc.gov)
- Collecting valid surveillance data may be challenging in azole resistance due to numerous factors that present potential biases. (ru.nl)
- Our list includes all the high-impact factor Azole journals that may be relevant to your field of study. (oa.mg)
- In contrast to their effects on the actinomycetes, the azoles showed minimal effects on the growth of Escherichia coli, which is devoid of P450s. (hud.ac.uk)
- Detailed analysis of key players, along with key growth strategies adopted by Phenyl Jiahuan Azole industry, the PEST and SWOT analysis are also included. (globalmarketmonitor.com)
- The report deep analyzes type and application in Japan Phenyl Jiahuan Azole market. (globalmarketmonitor.com)
- However, none of the azoles is safe to use in pregnancy and lactation because they have shown teratogenicity in animal studies. (medscape.com)