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Sample records for antifungal drugs posaconazole

  1. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

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    Mayur D. Mody MD

    2017-02-01

    Full Text Available Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  2. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

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    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  3. Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation.

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    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Queudeville, Manon; Feucht, Judith; Blaeschke, Franziska; Schlegel, Patrick; Feuchtinger, Tobias; Lang, Peter; Müller, Ingo; Handgretinger, Rupert; Heinz, Werner J

    2017-07-01

    Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients. This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined. No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups. Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.

  4. Comparative survival and cost of antifungal therapy: posaconazole versus standard antifungals in the treatment of refractory invasive aspergillosis.

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    Herbrecht, Raoul; Rajagopalan, Srinivasan; Danna, Robert; Papadopoulos, George

    2010-10-01

    Refractory invasive aspergillosis (IA) is a life-threatening condition. Cost of treatment, although secondary, is important if newer drugs are to be widely accepted. Posaconazole has been shown to have activity against aspergillosis. Analyses were conducted to compare the effectiveness and cost of posaconazole 800 mg/day with those of standard antifungal therapy, using Walsh et al. 2007 data. All-cause mortality and total drug costs were analyzed for three patient groups: All Refractory, Refractory Non-neutropenic, and Refractory Neutropenic IA Patients. Comparative survival analysis using Kaplan-Meier estimates after censoring data at 28, 42, 84, 182, and 365 days and Cox proportional hazard method was used to estimate hazard rates after controlling for difference in baseline neutropenia. For cost analysis, only antifungal drug acquisition cost was used. Significantly more of the 94 patients treated with posaconazole remained alive at every time point compared with the 68 external control patients within the All Refractory group (p = 0.0001). Similar results were obtained for the other two groups. For the posaconazole-treated patients mean total drug costs were $11846 (±$12406), $12642 (±$11811), and $8903 (±$14345), and for the external controls total drug costs were $35537 (±$73059), $48097 (±$88702), and $13556 (±$16324) for the All Refractory, Refractory Non-neutropenic, and Neutropenic IA groups, respectively. Key limitations of the study included noninclusion of hospitalization or other drug costs, low patient numbers beyond 84 days, and the fact that the Walsh et al. 2007 study was completed before other newer antifungal agents (such as voriconazole and caspofungin) were available. Posaconazole appears to confer a survival benefit and reduced total drug cost compared with standard antifungal therapy, such as amphotericin B (lipid and nonlipid formulations), itraconazole, or both, to treat patients with probable or proven refractory IA.

  5. Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia.

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    Döring, M; Eikemeier, M; Cabanillas Stanchi, K M; Hartmann, U; Ebinger, M; Schwarze, C-P; Schulz, A; Handgretinger, R; Müller, I

    2015-06-01

    Pediatric patients with hemato-oncological malignancies and neutropenia resulting from chemotherapy have a high risk of acquiring invasive fungal infections. Oral antifungal prophylaxis with azoles, such as fluconazole or itraconazole, is preferentially used in pediatric patients after chemotherapy. During this retrospective analysis, posaconazole was administered based on favorable results from studies in adult patients with neutropenia and after allogeneic hematopoietic stem cell transplantation. Retrospectively, safety, feasibility, and initial data on the efficacy of posaconazole were compared to fluconazole and itraconazole in pediatric and adolescent patients during neutropenia. Ninety-three pediatric patients with hemato-oncological malignancies with a median age of 12 years (range 9 months to 17.7 years) that had prolonged neutropenia (>5 days) after chemotherapy or due to their underlying disease, and who received fluconazole, itraconazole, or posaconazole as antifungal prophylaxis, were analyzed in this retrospective single-center survey. The incidence of invasive fungal infections in pediatric patients was low under each of the azoles. One case of proven aspergillosis occurred in each group. In addition, there were a few cases of possible invasive fungal infection under fluconazole (n = 1) and itraconazole (n = 2). However, no such cases were observed under posaconazole. The rates of potentially clinical drug-related adverse events were higher in the fluconazole (n = 4) and itraconazole (n = 5) groups compared to patients receiving posaconazole (n = 3). Posaconazole, fluconazole, and itraconazole are comparably effective in preventing invasive fungal infections in pediatric patients. Defining dose recommendations in these patients requires larger studies.

  6. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans.

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    Ying-Lien Chen

    Full Text Available The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.

  7. In vitro activity of the antifungal azoles itraconazole and posaconazole against Leishmania amazonensis.

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    Sara Teixeira de Macedo-Silva

    Full Text Available Leishmaniasis, caused by protozoan parasites of the Leishmania genus, is one of the most prevalent neglected tropical diseases. It is endemic in 98 countries, causing considerable morbidity and mortality. Pentavalent antimonials are the first line of treatment for leishmaniasis except in India. In resistant cases, miltefosine, amphotericin B and pentamidine are used. These treatments are unsatisfactory due to toxicity, limited efficacy, high cost and difficult administration. Thus, there is an urgent need to develop drugs that are efficacious, safe, and more accessible to patients. Trypanosomatids, including Leishmania spp. and Trypanosoma cruzi, have an essential requirement for ergosterol and other 24-alkyl sterols, which are absent in mammalian cells. Inhibition of ergosterol biosynthesis is increasingly recognized as a promising target for the development of new chemotherapeutic agents. The aim of this work was to investigate the antiproliferative, physiological and ultrastructural effects against Leishmania amazonensis of itraconazole (ITZ and posaconazole (POSA, two azole antifungal agents that inhibit sterol C14α-demethylase (CYP51. Antiproliferative studies demonstrated potent activity of POSA and ITZ: for promastigotes, the IC50 values were 2.74 µM and 0.44 µM for POSA and ITZ, respectively, and for intracellular amastigotes, the corresponding values were 1.63 µM and 0.08 µM, for both stages after 72 h of treatment. Physiological studies revealed that both inhibitors induced a collapse of the mitochondrial membrane potential (ΔΨm, which was consistent with ultrastructural alterations in the mitochondrion. Intense mitochondrial swelling, disorganization and rupture of mitochondrial membranes were observed by transmission electron microscopy. In addition, accumulation of lipid bodies, appearance of autophagosome-like structures and alterations in the kinetoplast were also observed. In conclusion, our results indicate that ITZ and

  8. Posaconazole plasma concentrations in pediatric patients receiving antifungal prophylaxis during neutropenia.

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    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Klinker, Hartwig; Eikemeier, Melinda; Feucht, Judith; Blaeschke, Franziska; Schwarze, Carl-Philipp; Ebinger, Martin; Feuchtinger, Tobias; Handgretinger, Rupert; Heinz, Werner J

    2017-06-01

    Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml). Age and gender had no influence on posaconazole plasma levels. Posaconazole was not discontinued due to adverse events in any of the patients. Only hepatic parameters significantly increased beyond the upper normal limit to median values of ALT of 87 U/l (P < .0001), and AST of 67 U/l (P < .0001). One patient with a median posaconazole trough concentration of 306 ng/ml experienced an invasive fungal infection. In conclusion, posaconazole was effective, safe and feasible in 33 pediatric patients with neutropenia ≥5 days after chemotherapy. Median posaconazole plasma concentrations were approximately 1.6-fold lower than the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to evaluate these findings. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations.

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    Walravens, Jeroen; Brouwers, Joachim; Spriet, Isabel; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2011-11-01

    Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose. A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola®] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola® following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined. Compared with administration with water, coadministration of Coca-Cola® did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p Coca-Cola® and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration-time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola® could not completely compensate for the

  10. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: investigating drug-polymer miscibility with advanced characterisation.

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    Fule, Ritesh; Amin, Purnima

    2014-01-01

    Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0-72) and C(max) of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0-72) and C(max) higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  11. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

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    Wei Sun

    Full Text Available A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug, tacrolimus (an immunosuppressive agent and floxuridine (an antimetabolite were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  12. Special Issue: Novel Antifungal Drug Discovery

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    Maurizio Del Poeta

    2016-12-01

    Full Text Available This Special Issue is designed to highlight the latest research and development on new antifungal compounds with mechanisms of action different from the ones of polyenes, azoles, and echinocandins. The papers presented here highlight new pathways and targets that could be exploited for the future development of new antifungal agents to be used alone or in combination with existing antifungals. A computational model for better predicting antifungal drug resistance is also presented.

  13. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

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    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data

  14. The Elements of Antifungal Drug Discovery

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    Kjellerup, Lasse

    compounds (ZACs). Zinc is an important micronutrient and the immune system is known to operate with a similar mechanism to the ZACs by scavenging zinc from the site of infection, thus preventing the growth of pathogens through zinc starvation. In addition to the observations made about the ZAC compounds......In this PhD thesis I will explore the development of antifungal drugs. Fungal infections are estimated to cause the death of 1.5 million patients each year. There is currently a need for new antifungal drugs as the existing drugs are hampered by lack of broad-spectrum antifungal activity...

  15. Tacrolimus Enhances the Potency of Posaconazole Against Rhizopus oryzae In Vitro and in an Experimental Model of Mucormycosis

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    Lewis, Russell E.; Ben-Ami, Ronen; Best, Leyla; Albert, Nathaniel; Walsh, Thomas J.; Kontoyiannis, Dimitrios P.

    2013-01-01

    Background. We hypothesized that tacrolimus, an inhibitor of the calcineurin pathway, would enhance the in vivo activity of posaconazole against Rhizopus oryzae, the Mucorales species most commonly associated with mucormycosis. Methods. We examined patterns of growth inhibition and fungicidal activity of posaconazole and tacrolimus, alone and in combination, against R. oryzae in vitro, using multiple methods (ie, hyphal metabolic and fluorescent vital dye reduction assays and measurement of chitin concentrations), and in vivo, using 2 mucormycosis models: an invertebrate model (Drosophila) and a nonlethal murine model of cutaneous mucormycosis. Results. Combinations of posaconazole and tacrolimus were synergistic in checkerboard assays for 4 clinical isolates of R. oryzae (48-hour fractional inhibitory concentration index, 0.187–0.281). Pharmacodynamic analysis of the combination revealed that the 90% effective concentration threshold of posaconazole activity against R. oryzae could be achieved with 2-fold lower drug concentrations (0.5–1 mg/L) when administered with tacrolimus (0.007–2 mg/L). In vivo, combination therapy was associated with improved survival in the fly model of mucormycosis (65% vs 57% posaconazole alone) and with significant reductions in cutaneous lesions and R. oryzae fungal burden, compared with animals that received posaconazole monotherapy, in the cutaneous model of mucormycosis. Conclusions. Combination posaconazole-tacrolimus therapy displays synergism in vitro and improved antifungal efficacy in vivo in 2 phylogenetically distinct models of mucormycosis. PMID:23242544

  16. Posaconazole: An Update of Its Clinical Use

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    Simon Leung

    2015-10-01

    Full Text Available Posaconazole (PCZ is a relatively new addition to the azole antifungals. It has fungicidal activities against Aspergillus fumigatus, Blastomyces dermatitidis, selected Candida species, Crytopcoccus neoformans, and Trichosporon. PCZ also has fungistatic activities against Candida, Coccidioides, selected Fusarium spp., Histoplasma, Scedosporium and Zygomycetes. In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against A. fumigatus, C. glabrata and C. neoformans. The absorption of PCZ suspension is enhanced when given with food, nutritional supplements, and carbonated beverages. Oral administration of PCZ in divided doses also increases its bioavailability. PCZ has a large volume of distribution and is highly protein bound (>95%. The main elimination route of PCZ is fecal. PCZ is an inhibitor of the CYP3A4 enzyme; therefore, monitoring for drug-drug interactions is warranted with other CYP3A4 substrates/inhibitors/inducers. The most common adverse effects include headache, fatigue, nausea, vomiting and elevated hepatic enzymes. PCZ, with its unique antifungal activities, expands the azole class of antifungal agents. Because of its limit in formulation, PCZ oral suspension is recommended in immunocompromised patients with functional gastrointestinaltracts who fail conventional antifungal therapies or who are suspected to have a breakthrough fungal infection. However, a delayed-release tablet formulation and intravenous (IV injection became available in 2014, expanding the use of PCZ in other patient populations, including individuals who are unable to take oral formulations.

  17. Mineralocorticoid hypertension and hypokalaemia induced by posaconazole

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    Boughton, Charlotte; Taylor, David; Ghataore, Lea; Taylor, Norman; Whitelaw, Benjamin C

    2018-01-01

    Summary We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortison...

  18. Tolerability and safety of antifungal drugs

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    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  19. Mineralocorticoid hypertension and hypokalaemia induced by posaconazole.

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    Boughton, Charlotte; Taylor, David; Ghataore, Lea; Taylor, Norman; Whitelaw, Benjamin C

    2018-01-01

    We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone. We also suggest that posaconazole may cause cortisol insufficiency. Patients taking posaconazole should therefore be monitored for hypokalaemia, hypertension and symptoms of hypocortisolaemia, at the onset of treatment and on a monthly basis. Treatment with mineralocorticoid antagonists (spironolactone or eplerenone), supplementation of glucocorticoids (e.g. hydrocortisone) or dose reduction or cessation of posaconazole should all be considered as management strategies. Combined hypertension and hypokalaemia are suggestive of mineralocorticoid excess; further investigation is appropriate.If serum aldosterone is suppressed, then further investigation to assess for an alternative mineralocorticoid is appropriate, potentially using urine steroid profiling and/or serum steroid panelling.Posaconazole can cause both hypokalaemia and hypertension, and we propose that this is due to two mechanisms - both 11β hydroxylase inhibition and 11β HSD2 inhibition.Posaconazole treatment may lead to cortisol insufficiency, which may require treatment; however, in this clinical case, the effect was mild.First-line treatment of this presentation would likely be use of a mineralocorticoid antagonist.Patients taking posaconazole should be monitored for hypertension and hypokalaemia on initiation and monthly thereafter.

  20. Use of Intravenous Posaconazole in Hematopoietic Stem Cell Transplant Patients.

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    Strommen, Amanda; Hurst, Amanda L; Curtis, Donna; Abzug, Mark J

    2018-01-05

    Posaconazole is a broad-spectrum antifungal used for prophylaxis and treatment of invasive fungal infections. There is no published data to inform prescribers on dosing of the intravenous (IV) formulation in the pediatric population. We describe our experience including dosing, serum concentrations, and tolerability. Four patients (3 to 9 y) received IV posaconazole for treatment of documented/suspected invasive fungal infections. Patients achieved therapeutic concentrations on daily doses of 8.4 to 12.2 mg/kg and adverse effects were minimal. Higher dosing per body weight of IV posaconazole may be required in the pediatric population compared with adults to consistently achieve therapeutic concentrations.

  1. Molecular basis of antifungal drug resistance in yeasts

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    Morio, Florent; Jensen, Rasmus Hare; Le Pape, Patrice

    2017-01-01

    Besides inherent differences in in vitro susceptibilities, clinically-relevant yeast species may acquire resistance upon exposure to most antifungal drugs used in the clinic. In recent years, major fundamental research studies have been conducted to improve our understanding of the molecular basis......., in the context of antifungal drug resistance. Also included are the methods currently available for in vitro antifungal susceptibility testing and for molecular detection of mutations associated with resistance. Finally, the genetic drivers of antifungal resistance are discussed in light of the spectra...

  2. Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole.

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    Wadsworth, John M; Milan, Anna M; Anson, James; Davison, Andrew S

    2017-11-01

    Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R 2  = 0.995) and 5 mg/L for posaconazole (R 2  = 0.990) and itraconazole (R 2  = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring.

  3. In vitro activities of antifungal drugs against environmental Exophiala isolates and review of the literature.

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    Gülmez, Dolunay; Doğan, Özlem; Boral, Barış; Döğen, Aylin; İlkit, Macit; de Hoog, G Sybren; Arikan-Akdagli, Sevtap

    2018-04-03

    Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardized. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48h, 72h, and 96h. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine, to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48h for all isolates except two Exophiala dermatitidis strains. At 72h, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole, and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

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    Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

    2013-09-01

    The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen. © 2013 Blackwell Verlag GmbH.

  5. Fixed Drug Eruptions To Two Chemically Unrelated Antifungal Agents

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    Khandpur Sujay

    2001-01-01

    Full Text Available An interesting episode of fixed drug eruption to two chemically unrelated antifungal agents (griseofulvin and fluconazole prescribed for onychomycosis in a 66- year â€" old male is being presented. The lesions developed at different sites. Oral challenge led to recurrence with both the drugs. However patch test with 10% fluconazole in petrolatum was negative.

  6. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    Coleman, David C

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  7. Antifungal drug susceptibility of Candida albicans | Bii | East African ...

    African Journals Online (AJOL)

    Objective: To determine the susceptibility of clinical isolates of Candida albicans and to establish the minimum inhibitory concentrations (MIC) to commonly used antifungal drugs. Design: Laboratory based experiment. Setting: Mbagathi District Hospital, Nairobi, Kenya. Subjects: Candida albicans isolated between 1998 ...

  8. Mode of Antifungal Drugs Interaction with Cytochrome P- 450

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    M- Mahmodian

    1991-07-01

    Full Text Available Computer was used to identify the interactions of substrates and antifungal drugs with the enzyme, Cytochrome P-450; and then Molplot.bas computer program was applied to get three dimensional figures of 5-hydroxy camphor.oxidation products of camphor analogues, and antifungal drugs.Cartesian characteristics of atoms building molecules, are taken from Buildz. for program, which can calculate X,Y,Z coordinates of atoms by Zmatrix data. The other program which can calculate X,Y,Z coordinates, using fractional characteristics, is the Coord, for program that, gives our cartesian characteristics of the atoms of molecule, then by using these data, we obtain three dimensional figures and distance between active atoms in compounds under consideration. Results show that distance between two oxygen atoms in 5-exo-hydroxy- camphor and the other compounds obtained from oxidation of camphor analogues, with the distance of two oxygen atoms in antifungal compounds under discussion are equal. Therefore, we can conclude that, the antifungal molecule also interacts with enzyme's active site, by its own sites, in a similar manner to the 5-hydroxy camphor molecule, which is:"n1. Nitrogen atom (N of Imidazole and Triazole ring in antifungal molecule with Iron atom in heam molecule belonging to Cytochrome P-450 enzyme, are coordinated."n2. The other atoms such as : 0,S or N in structure of the antifungal drug are coordinated with hydrogen atom of hydroxyl group belong ing to Tyr-96 in the structure of enzyme, forming hydrogen bonding.

  9. Successful Use of Posaconazole to Treat Invasive Cutaneous Fungal Infection in a Liver Transplant Patient on Sirolimus

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    Randah Dahlan

    2012-01-01

    Full Text Available Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.

  10. Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole

    DEFF Research Database (Denmark)

    Dybro, Anne Mette; Damkier, Per; Rasmussen, Torsten Bloch

    2016-01-01

    -associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole...... antifungal agents such as itraconazole and posaconazole. If antifungal treatment is indicated in a patient using a CYP3A4-metabolised statin, we recommend (1) topical administration of the antifungal agent if possible, (2) the use of a non-CYP3A4-inhibiting antifungal drug such as terbinafine or (3...

  11. Evaluation and optimized selection of supersaturating drug delivery systems of posaconazole (BCS class 2b) in the gastrointestinal simulator (GIS): An in vitro-in silico-in vivo approach.

    Science.gov (United States)

    Hens, Bart; Bermejo, Marival; Tsume, Yasuhiro; Gonzalez-Alvarez, Isabel; Ruan, Hao; Matsui, Kazuki; Amidon, Gregory E; Cavanagh, Katie L; Kuminek, Gislaine; Benninghoff, Gail; Fan, Jianghong; Rodríguez-Hornedo, Naír; Amidon, Gordon L

    2018-03-30

    Supersaturating drug delivery systems (SDDS) have been put forward in the recent decades in order to circumvent the issue of low aqueous solubility. Prior to the start of clinical trials, these enabling formulations should be adequately explored in in vitro/in silico studies in order to understand their in vivo performance and to select the most appropriate and effective formulation in terms of oral bioavailability and therapeutic outcome. The purpose of this work was to evaluate the in vivo performance of four different oral formulations of posaconazole (categorized as a biopharmaceutics classification system (BCS) class 2b compound) based on the in vitro concentrations in the gastrointestinal simulator (GIS), coupled with an in silico pharmacokinetic model to predict their systemic profiles. Recently published intraluminal and systemic concentrations of posaconazole for these formulations served as a reference to validate the in vitro and in silico results. Additionally, the morphology of the formed precipitate of posaconazole was visualized and characterized by optical microscopy studies and thermal analysis. This multidisciplinary work demonstrates an in vitro-in silico-in vivo approach that provides a scientific basis for screening SDDS by a user-friendly formulation predictive dissolution (fPD) device in order to rank these formulations towards their in vivo performance. Copyright © 2018. Published by Elsevier B.V.

  12. Clinico-mycological study of dermatophytic infections and their sensitivity to antifungal drugs in a tertiary care center

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    Soniya Mahajan

    2017-01-01

    Conclusion: Inadequate and irregular use of antifungal drugs has led to the emergence of resistant strains, which cause poor treatment outcomes. Thus, it is very important to test for antifungal sensitivity to check for resistance to antifungals.

  13. Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

    Science.gov (United States)

    Launay, Manon; Roux, Antoine; Beaumont, Laurence; Douvry, Benoit; Lecuyer, Lucien; Douez, Emmanuel; Picard, Clément; Grenet, Dominique; Jullien, Vincent; Boussaud, Véronique; Guillemain, Romain; Billaud, Eliane M

    2018-03-01

    Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations ( C 0 ) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were asterisk means that statistical test is significant]), and the PSZ C 0 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively ( P < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL C 0 /dose ratio ( C 0 / D ) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution ( P = 0.034*). The ERL C 0 / D was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; P = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients. Copyright © 2018 American Society for Microbiology.

  14. Posaconazole-Induced Adrenal Insufficiency in a Case of Chronic Myelomonocytic Leukemia

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    Ann Miller

    2018-01-01

    Full Text Available Introduction. Posaconazole is an azole used in treatment and prophylaxis of a broad spectrum of fungal infections. Antifungals such as ketoconazole have been shown to cause primary adrenal insufficiency (AI as a result of direct inhibition on the steroidogenesis pathway. There is only one reported case of primary AI induced by posaconazole in a patient with mucormycosis. We report a case of posaconazole-related primary AI. Case. A 63-year-old man with chronic myelomonocytic leukemia was admitted for fatigue and intermittent nausea and vomiting. He had recently discontinued prophylactic posaconazole 300 mg daily. He was assessed for AI with a morning cortisol of 1.9 mcg/dL followed by a failed cosyntropin stimulation (CS test. Adrenocorticotropic hormone (ACTH level was 154.6 pg/mL with negative 21-hydroxylase antibodies. The patient’s symptoms improved with initiation of hydrocortisone and fludrocortisone. One year after discontinuation of posaconazole, he underwent a repeat CS test which showed normal adrenal function with normal ACTH at 34.1 pg/mL. Conclusion. In this case, we demonstrate that prolonged use of posaconazole is associated with primary AI. As use of posaconazole increases, knowledge of the potential risk of AI is important and must be included in the differential diagnosis when these patients present with hypotension, hypoglycemia, and failure to thrive.

  15. Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011

    Science.gov (United States)

    Asmundsdottir, Lena Ros; Erlendsdottir, Helga

    2013-01-01

    Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year; P = 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (P 60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (P = 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%, P = 0.97). Candida albicans was the predominant species (56%), followed by C. glabrata (16%) and C. tropicalis (13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates. PMID:23269738

  16. Drug-drug interactions of antifungal agents and implications for patient care.

    Science.gov (United States)

    Gubbins, Paul O; Amsden, Jarrett R

    2005-10-01

    Drug interactions in the gastrointestinal tract, liver and kidneys result from alterations in pH, ionic complexation, and interference with membrane transport proteins and enzymatic processes involved in intestinal absorption, enteric and hepatic metabolism, renal filtration and excretion. Azole antifungals can be involved in drug interactions at all the sites, by one or more of the above mechanisms. Consequently, azoles interact with a vast array of compounds. Drug-drug interactions associated with amphotericin B formulations are predictable and result from the renal toxicity and electrolyte disturbances associated with these compounds. The echinocandins are unknown cytochrome P450 substrates and to date are relatively devoid of significant drug-drug interactions. This article reviews drug interactions involving antifungal agents that affect other agents and implications for patient care are highlighted.

  17. Antifungal therapy: drug-drug interactions at your fingertips

    NARCIS (Netherlands)

    Lempers, V.J.; Bruggemann, R.J.

    2016-01-01

    The Information Age has revolutionized the ability of healthcare professionals (HCPs) to oversee a substantial body of clinically relevant information literally at one's fingertips. In the field of clinical pharmacology, this may be particularly useful for managing drug-drug interactions (DDIs). A

  18. Comparative Pharmacodynamics of Posaconazole in Neutropenic Murine Models of Invasive Pulmonary Aspergillosis and Mucormycosis

    Science.gov (United States)

    Albert, Nathaniel D.

    2014-01-01

    We used two established neutropenic murine models of pulmonary aspergillosis and mucormycosis to explore the association between the posaconazole area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC) and treatment outcome. Posaconazole serum pharmacokinetics were verified in infected mice to ensure that the studied doses reflected human exposures with the oral suspension, delayed-release tablet, and intravenous formulations of posaconazole. Sinopulmonary infections were then induced in groups of neutropenic mice with Aspergillus fumigatus strain 293 (posaconazole MIC, 0.5 mg/liter) or Rhizopus oryzae strain 969 (posaconazole MIC, 2 mg/liter) and treated with escalating daily dosages of oral posaconazole, which was designed to achieve AUCs ranging from 1.10 to 392 mg · h/liter. After 5 days of treatment, lung fungal burden was analyzed by quantitative real-time PCR. The relationships of the total drug AUC/MIC and the treatment response were similar in both models, with 90% effective concentrations (EC90s) corresponding to an AUC/MIC threshold of 76 (95% confidence interval [CI], 46 to 102) for strain 293 versus 87 (95% CI, 66 to 101) for strain 969. Using a provisional AUC/MIC target of >100, these exposures correlated with minimum serum posaconazole concentrations (Cmins) of 1.25 mg/liter for strain 293 and 4.0 mg/liter for strain 969. The addition of deferasirox, but not liposomal amphotericin or caspofungin, improved the activity of a suboptimal posaconazole regimen (AUC/MIC, 33) in animals with pulmonary mucormycosis. However, no combination was as effective as the high-dose posaconazole monotherapy regimen (AUC/MIC, 184). Our analysis suggests that posaconazole pharmacodynamics are similar for A. fumigatus and R. oryzae when indexed to pathogen MICs. PMID:25182639

  19. In Vitro Antifungal Susceptibility of Oral Candida Isolates from Patients Suffering from Caries and Chronic Periodontitis.

    Science.gov (United States)

    De-la-Torre, Janire; Ortiz-Samperio, María Esther; Marcos-Arias, Cristina; Marichalar-Mendia, Xabier; Eraso, Elena; Echebarria-Goicouria, María Ángeles; Aguirre-Urizar, José Manuel; Quindós, Guillermo

    2017-06-01

    Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

  20. Rhino-orbital Mucormycosis Treated Successfully with Posaconazole without Exenteration.

    Science.gov (United States)

    Zhang, Jason; Kim, James D; Beaver, Hilary A; Takashima, Masayoshi; Lee, Andrew G

    2013-01-01

    Mucormycosis is a rare and often fatal opportunistic angioinvasive infection seen mostly in immunocompromised patients, such as those with diabetes mellitus, cancer, or renal failure. Ophthalmic manifestations of orbital mucormycosis include ocular pain, periocular oedema, visual loss, ophthalmoplegia, proptosis, and ptosis. Although therapy for orbital mucormycosis consists of maximally tolerated doses of antifungal agents (e.g., amphotericin B) and extensive surgical debridement, treatment remains ineffective in up to 20% of cases. We describe two patients with rhino-orbitalmucormycosis who were successfully treated with posaconazole in conjunction with intravenous (IV) amphotericin B and sinus surgical debridement. These cases highlight several unusual early manifestations of orbital mucormycosis, including disc oedema and amaurosis fugax, as well as the applicability of a new extended-spectrum antifungal agent in management of orbital zygomycosis.

  1. Quantitative and qualitative analysis of the antifungal activity of allicin alone and in combination with antifungal drugs.

    Directory of Open Access Journals (Sweden)

    Young-Sun Kim

    Full Text Available The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB were investigated in Candida albicans (C. albicans. C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine. After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM and atomic force microscopy (AFM to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes. Classification of cells according to their cell death phase (CDP allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy.

  2. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi.

    Science.gov (United States)

    Veiga-Santos, Phercyles; Barrias, Emile S; Santos, Júlio F C; de Barros Moreira, Thiago Luiz; de Carvalho, Tecia Maria Ulisses; Urbina, Julio A; de Souza, Wanderley

    2012-07-01

    The antifungal posaconazole (PCZ) is the most advanced candidate for the treatment of Chagas disease, having potent anti-Trypanosoma cruzi activity in vitro and in animal models of the disease as well as an excellent safety profile in humans. Amiodarone (AMD) is the antiarrhythmic drug most frequently used for the symptomatic treatment of chronic Chagas disease patients, but it also has specific anti-T. cruzi activity. When used in combination, these drugs exhibit potent synergistic activity against the parasite. In the present work, electron microscopy was used to analyse the effects of both compounds, acting individually or in combination, against T. cruzi. The 50% inhibitory concentration (IC(50)) against epimastigote and amastigote forms was 25 nM and 1.0 nM for PCZ and 8 μM and 5.6 μM for AMD, respectively. The antiproliferative synergism of the drugs (fractional inhibitory concentrationanti-T. cruzi therapy with low side effects. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  3. Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

    Science.gov (United States)

    Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

    2016-10-01

    Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  4. Adverse events of modern antifungal drugs during treatment of invasive fungal infections

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    N. V. Dmitrieva

    2013-01-01

    Full Text Available Characteristics of adverse events of modern antimycotics by organ systems and comparative frequency between different medicines and their groups are presented. The examples of incompatibility of antifungal drugs with other pharmacological groups are discussed. Records of adverse events and drug compatibility will allow the practitioner to prevent and timely cure possible complications, should they arise.

  5. Treatment of Mucormycosis with Liposomal Amphotericin B, Posaconazole and Deferasirox: A Case Report

    Directory of Open Access Journals (Sweden)

    Uğur Önal

    2016-03-01

    Full Text Available In this paper, we present a 69 years old diabetic patient with mucormycosis who was succesfully treated with liposomal amphotericin B (LAMB, posaconazole and deferasirox despite having no adequate surgery. There was no relapse on 6 month post-treatment follow-up. We conclude that combination of antifungal antibiotics with deferasirox may be successful in the salvage therapy of mucormycosis especially in diabetic patients. J Microbiol Infect Dis 2016;6(1: 32-35

  6. Candidiasis and the impact of flow cytometry on antifungal drug discovery.

    Science.gov (United States)

    Ku, Tsun Sheng N; Bernardo, Stella; Walraven, Carla J; Lee, Samuel A

    2017-11-01

    Invasive candidiasis continues to be associated with significant morbidity and mortality as well as substantial health care costs nationally and globally. One of the contributing factors is the development of resistance to antifungal agents that are already in clinical use. Moreover, there are known treatment limitations with all of the available antifungal agents. Since traditional techniques in novel drug discovery are time consuming, high-throughput screening using flow cytometry presents as a potential tool to identify new antifungal agents that would be useful in the management of these patients. Areas covered: In this review, the authors discuss the use of automated high-throughput screening assays based upon flow cytometry to identify potential antifungals from a library comprised of a large number of bioactive compounds. They also review studies that employed the use of this research methodology that has identified compounds with antifungal activity. Expert opinion: High-throughput screening using flow cytometry has substantially decreased the processing time necessary for screening thousands of compounds, and has helped enhance our understanding of fungal pathogenesis. Indeed, the authors see this technology as a powerful tool to help scientists identify new antifungal agents that can be added to the clinician's arsenal in their fight against invasive candidiasis.

  7. Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.

    Directory of Open Access Journals (Sweden)

    Lívia de Figueiredo Diniz

    Full Text Available Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo.Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days, followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk followed by posaconazole (20 mpk provided cure rates comparable to those obtained with the full (20 days treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone.Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive

  8. Usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment.

    Science.gov (United States)

    Nakama, Tatsuya; Yamashita, Satoshi; Hirahara, Tomoo; Okamoto, Sadahisa; Honda, Shoji; Watanabe, Masaki; Kimura, En; Uchino, Makoto; Yano, Shigetoshi; Kuratsu, Jun-ichi; Ando, Yukio

    2015-11-15

    Cryptococcal meningitis is a severe infection among immunosuppressed individuals, with a high mortality rate. Although amphotericin B is the first-choice drug for treatment, its use is restricted when adverse effects are clinically problematic. The usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment has been unconfirmed. We evaluated the efficacy of intraventricular infusion of amphotericin B through Ommaya reservoirs. We retrospectively analyzed 10 consecutive patients with cryptococcal meningitis who were refractory to systemic administration of antifungal drugs. Fever or nausea occurred in most patients. However, no patient complained of serious complications such as renal toxicity. Seven patients recovered completely or partially, whereas three patients died. To establish the efficacy of the intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis, a prospective investigation should be designed to compare those treated according to the updated guidelines and those treated with antifungal drugs through the Ommaya reservoirs. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance.

    Science.gov (United States)

    Biswas, Chayanika; Chen, Sharon C-A; Halliday, Catriona; Martinez, Elena; Rockett, Rebecca J; Wang, Qinning; Timms, Verlaine J; Dhakal, Rajat; Sadsad, Rosemarie; Kennedy, Karina J; Playford, Geoffrey; Marriott, Deborah J; Slavin, Monica A; Sorrell, Tania C; Sintchenko, Vitali

    2017-12-28

    Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was torecognize enablers and barriers in the implementation WGS and measure its effectiveness. This paper outlines the key quality control checkpoints and essential components of WGS methodology to investigate genetic markers associated with reduced susceptibility to antifungal agents. It also estimates the accuracy of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12 clinical, and one ATCC strain of C. glabrata was determined through antifungal susceptibility testing. These included three isolate pairs, from three patients, that developed rise in drug minimum inhibitory concentrations. In two pairs, the second isolate of each pair developed resistance to echinocandins. The second isolate of the third pair developed resistance to 5-flucytosine. The remaining comprised of susceptible and azole resistant isolates. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine resistance were confirmed in resistant isolates through WGS using the next generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98% of the WGS reads of C. glabrata isolates mapped to the reference genome with about 75-fold read depth coverage. The turnaround time and cost were comparable to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing clinically significant gene mutations involved in resistance to different antifungal drug classes without the need for multiple PCR/DNA sequencing reactions. This represents a

  10. Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales

    NARCIS (Netherlands)

    Vitale, R.G.; de Hoog, G.S.; Schwarz, P.; Dannaoui, E.; Deng, S.; Machouart, M.; Voigt, K.; de Sande, W.W.J.v.; Dolatabadi, S.; Meis, J.F.; Walther, G.

    2012-01-01

    The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear

  11. Antifungal susceptibility and phylogeny of opportunistic members of the order Mucorales

    NARCIS (Netherlands)

    R.G. Vitale (Roxana); G.S. de Hoog; P. Schwarz (Peter); E. Dannaoui (Eric); S. Deng (Shuwen); M. Machouart (Marie); K. Voigt (Kerstin); W.W.J. van de Sande (Wendy); S. Dolatabadi (Somayeh); J.F. Meis; G. Walther

    2012-01-01

    textabstractThe in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the

  12. Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales.

    NARCIS (Netherlands)

    Vitale, R.G.; Hoog, G.S. de; Schwarz, P.; Dannaoui, E.; Deng, S.; Machouart, M.; Voigt, K.; Sande, W.W. van de; Dolatabadi, S.; Meis, J.F.G.M.; Walther, G.

    2012-01-01

    The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear

  13. Drug Repurposing Approach Identifies a Synergistic Drug Combination of an Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.

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    Riedel, Tina; Demaria, Olivier; Zava, Olivier; Joncic, Ana; Gilliet, Michel; Dyson, Paul J

    2018-01-02

    By screening a drug library comprising FDA approved compounds, we discovered a potent interaction between the antifungal agent haloprogin and the experimental organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The combination of these two small molecules, even at low doses, elicited an improved therapeutic response on tumor growth over either agent alone or the current treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma tumor model, where classical cytotoxic chemotherapeutic agents show little efficacy. The combination with the repurposed chemodrug haloprogin provides the basis for a new powerful treatment option for cutaneous melanoma. Importantly, because synergistic induction of tumor cell death is achieved with low individual drug doses, and cellular targets for RAPTA-T are different from those of classical chemotherapeutic drugs, a therapeutic strategy based on this approach could avoid toxicities and potentially resistance mechanisms, and could even inhibit metastatic progression.

  14. Anti-Candida albicans natural products, sources of new antifungal drugs: A review.

    Science.gov (United States)

    Zida, A; Bamba, S; Yacouba, A; Ouedraogo-Traore, R; Guiguemdé, R T

    2017-03-01

    Candida albicans is the most prevalent fungal pathogen in humans. Due to the development of drug resistance, there is today a need for new antifungal agents for the efficient management of C. albicans infections. Therefore, we reviewed antifungal activity, mechanisms of action, possible synergism with antifungal drugs of all natural substances experimented to be efficient against C. albicans for future. An extensive and systematic review of the literature was undertaken and all relevant abstracts and full-text articles analyzed and included in the review. A total of 111 documents were published and highlighted 142 anti-C. albicans natural products. These products are mostly are reported in Asia (44.37%) and America (28.17%). According to in vitro model criteria, from the 142 natural substances, antifungal activity can be considered as important for 40 (28.20%) and moderate for 24 (16.90%). Sixteen products have their antifungal activity confirmed by in vivo gold standard experimentation. Microbial natural products, source of antifungals, have their antifungal mechanism well described in the literature: interaction with ergosterol (polyenes), inhibition 1,3-β-d-glucan synthase (Echinocandins), inhibition of the synthesis of cell wall components (chitin and mannoproteins), inhibition of sphingolipid synthesis (serine palmitoyltransferase, ceramide synthase, inositol phosphoceramide synthase) and inhibition of protein synthesis (sordarins). Natural products from plants mostly exert their antifungal effects by membrane-active mechanism. Some substances from arthropods are also explored to act on the fungal membrane. Interestingly, synergistic effects were found between different classes of natural products as well as between natural products and azoles. Search for anti-C. albicans new drugs is promising since the list of natural substances, which disclose activity against this yeast is today long. Investigations must be pursued not only to found more new anti

  15. Pharmacokinetics and Pharmacodynamics of Antifungals in Children and their Clinical Implications

    Science.gov (United States)

    Stockmann, Chris; Constance, Jonathan E.; Roberts, Jessica K.; Olson, Jared; Doby, Elizabeth H.; Ampofo, Krow; Stiers, Justin; Spigarelli, Michael G.

    2017-01-01

    Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected

  16. Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

    Energy Technology Data Exchange (ETDEWEB)

    Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando; Lepesheva, Galina I.

    2017-05-01

    ABSTRACT

    Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct

  17. Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Brito-Santos, Fábio; Figueiredo-Carvalho, Maria Helena Galdino; Machado, Ana Caroline Sá; Oliveira, Manoel Marques Evangelista; Pereira, Sandro Antonio; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely Maria

    2017-05-01

    Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.

  18. Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

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    Rodrigo Almeida-Paes

    Full Text Available BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs are available. In this situation, minimal inhibitory concentration (MIC distributions and epidemiological cutoff values (ECVs support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB, itraconazole (ITR, ketoconazole (KET, posaconazole (POS, and terbinafine (TRB against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.

  19. Oropharyngeal candidiasis and resistance to antifungal drugs in patients receiving radiation for head and neck cancer

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    Maryam Rad DMD, MSc

    2012-04-01

    Full Text Available BACKGROUND: Oropharyngeal candidiasis is a common infection in patient receiving radiotherapy for head and neckcancer. Accurate and rapid identification of candida species is very important in clinical laboratory, because theincidence of candidiasis continues to rise after radiotherapy. The genus Candida has about 154 species that showdifferent level of resistance to antifungal drugs and have high degree of phenotypic similarity. The aim of this study wasto investigate oral yeast colonization and infection and resistance to antifungal drugs in these patients.METHODS: Thirty patients receiving a 6-week course of radiation therapy for treatment of head and neck cancer at theOncology Unit in Shafa Hospital, in 2008, were enrolled in the study. Specimens from patients were cultured weeklyfor Candida. All isolates were plated on CHROM agar and RPMI-based medium. They were subcultured and submittedfor antifungal susceptibility testing (nystatin, fluconazole, clotrimazole and ketoconazole and molecular typing.RESULTS: Infection (clinical and microbiological evidence occurred in 50% of the patients and Candida colonization(only microbiological evidence occurred in 70% of subjects in the first week. Candida albicans alone was isolated in94.9% of patient visits with positive cultures. Candida tropicalis was isolated from 5.1% of patient visits with positivecultures. All isolates were susceptible to nystatin, but did not respond to the other antifungal drugsCONCLUSIONS: The irradiation-induced changes of the intraoral environment such as xerostomia lead to increasedintraoral colonization by Candida species. All yeast isolates were susceptible to nystatin. Thus prophylactic therapywith nystatin should be considered for these patients.

  20. Synergistic activity of antifungal drugs and lipopeptide AC7 against Candida albicans biofilm on silicone

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    Chiara Ceresa

    2017-04-01

    Full Text Available The occurrence of Candida albicans device-associated infections is tightly correlated to the ability of this fungus to form biofilms. The presence of this three-dimensional structure protects cells from host defenses, and significantly increases their resistance to antifungal agents. Lipopeptide biosurfactants are microbial products with interesting antibacterial, antifungal and anti-adhesive properties. Aim of the present study was to investigate a possible synergistic effect of lipopeptide AC7BS in combination with amphotericin B or fluconazole against C. albicans planktonic cells, biofilm formation and 24 h-old biofilms on medical-grade silicone elastomer disks, in simulated physiological conditions. In co-incubation experiments, AC7BS alone was not effective. However, the combination of AC7BS with the antifungal compounds resulted in a synergistic increase in the efficacy of the drugs against planktonic cells and biofilm, leading to a reduction of MICs and SMICs50. In pre-coating conditions, amphotericin B alone and AC7BS alone significantly inhibited C. albicans biofilms. When the two molecules were tested in association, a synergistic effect was observed on different phases of biofilm formation and a lower SMIC50 was detected. The observed synergism could be related to the combination of the AC7BS anti-adhesive activity and the AMB antifungal effect, but also to the ability of the biosurfactant to affect membranes, thus facilitating AMB entry in the cells. These results suggest that AC7BS can be considered a potential inhibitor of C. albicans biofilm on medical insertional materials and its use as coating agent may potentiate the effect of antifungal compounds such as AMB, when applied in combination.

  1. [Pharmacology of the antifungals used in the treatment of aspergillosis].

    Science.gov (United States)

    Azanza, José Ramón; Sádaba, Belén; Gómez-Guíu, Almudena

    2014-01-01

    The treatment of invasive aspergillosis requires the use of drugs that characteristically have complex pharmacokinetic properties, the knowledge of which is essential to achieve maximum efficacy with minimal risk to the patient. The lipid-based amphotericin B formulations vary significantly in their pharmacokinetic behaviour, with very high plasma concentrations of the liposomal form, probably related to the presence of cholesterol in their structure. Azoles have a variable absorption profile, particularly in the case of itraconazole and posaconazole, with the latter very dependent on multiple factors. This may also lead to variations in voriconazole, which requires considering the possibility of monitoring plasma concentrations. The aim of this article is to review some of the most relevant aspects of the pharmacology of the antifungals used in the prophylaxis and treatment of the Aspergillus infection. For this reason, it includes the most relevant features of some of the azoles normally prescribed in this infection (itraconazole, posaconazole and voriconazole) and the amphotericin B formulations. Copyright © 2014. Published by Elsevier Espana.

  2. Repurposing antipsychotic drugs into antifungal agents: Synergistic combinations of azoles and bromperidol derivatives in the treatment of various fungal infections.

    Science.gov (United States)

    Holbrook, Selina Y L; Garzan, Atefeh; Dennis, Emily K; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2017-10-20

    As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles. Exploring combination therapy that involves the current azoles and another drug has been shown to be a promising strategy. Haloperidol and its derivative, bromperidol, were originally discovered as antipsychotics. Herein, we synthesize and report a series of bromperidol derivatives and their synergistic antifungal interactions in combination with a variety of current azole antifungals against a wide panel of fungal pathogens. We further select two representative combinations and confirm the antifungal synergy by performing time-kill assays. Furthermore, we evaluate the ability of selected combinations to destroy fungal biofilm. Finally, we perform mammalian cytotoxicity assays with the representative combinations against three mammalian cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Iatrogenic Cushing's syndrome induced by posaconazole.

    Science.gov (United States)

    Pilmis, Benoit; Coignard-Biehler, Hélène; Jullien, Vincent; Hermine, Olivier; Touraine, Philippe; Lecuit, Marc; Lortholary, Olivier

    2013-11-01

    Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome. We present a patient with common-variable immunodeficiency who received 7 years of itraconazole therapy for bronchial colonization with Aspergillus in combination with inhaled fluticasone without any Cushingoid symptoms. After a switch to posaconazole, the patient developed Cushingoid symptoms.

  4. Proteomic profiling of the antifungal drug response of Aspergillus fumigatus to voriconazole.

    Science.gov (United States)

    Amarsaikhan, Nansalmaa; Albrecht-Eckardt, Daniela; Sasse, Christoph; Braus, Gerhard H; Ogel, Zumrut B; Kniemeyer, Olaf

    2017-10-01

    Antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (IA). Voriconazole has become a standard therapeutic for the treatment of this often fatal infection. We studied the differentially expressed proteins as a response of Aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (DIGE) technique. Due to addition of drug, a total of 135 differentially synthesized proteins were identified by MALDI-TOF/TOF-mass spectrometry. In particular, the level of proteins involved in the general stress response and cell detoxification increased prominently. In contrast, cell metabolism and energy proteins were down-regulated, which suggests the cellular effort to maintain balance in energy utilization while trying to combat the cellular stress exerted by the drug. We detected several so-far uncharacterized proteins which may play a role in stress response and drug metabolism and which could be future targets for antifungal treatment. A mutant strain, which is deleted in the cross-pathway control gene cpcA, was treated with voriconazole to investigate the contribution of the general control of amino acid biosynthesis to drug resistance. We compared the mutant strain's protein expression profile with the wild-type strain. The absence of CpcA led to an increased resistance to voriconazole and a reduced activation of some general stress response proteins, while the transcript level of the triazole target gene erg11A (cyp51A) remained unchanged. In contrast, the sensitivity of strain ΔcpcA to terbinafine and amphotericin B was slightly increased. These findings imply a role of CpcA in the cellular stress response to azole drugs at the post transcriptional level. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. In vitro activities of four antifungal drugs against Trichophyton rubrum isolates exhibiting resistance to fluconazole.

    Science.gov (United States)

    Santos, D A; Hamdan, J S

    2007-07-01

    Thirty-two clinical isolates of Trichophyton rubrum exhibiting resistance to fluconazole [minimum inhibitory concentrations (MICs) > or = 64 microg ml(-1)] were selected to test the antifungal activity of ketoconazole, itraconazole, griseofulvin and terbinafine. We followed the guidelines of the National Committee for Clinical Laboratory Standards for testing filamentous fungi. The strains Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), T. rubrum (ATCC 40051) and Trichophyton mentagrophytes (ATCC 40004) were included for quality control. The microdilution plates were incubated at 28 degrees C and were read visually after 7 days of incubation and endpoint determination readings were performed visually. The MIC ranges for the four antifungals were: 0.0625-2 microg ml(-1) for ketoconazole, 0.25-2.0 microg ml(-1) for griseofulvin, < or =0.031-1.0 microg ml(-1) for itraconazole and < or =0.031 microg ml(-1) for terbinafine (for all tested isolates). Terbinafine was the most potent drug against T. rubrum, in vitro, followed by itraconazole, ketoconazole and griseofulvin. Much work is still needed to correlate the MICs of these drugs with clinical outcomes to develop interpretative breakpoints for T. rubrum and other dermatophytes.

  6. Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

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    Valter Luis Iost Teodoro

    2013-12-01

    Full Text Available Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%, Cryptococcus gattii (5.2%, Cryptococcus ater (3.5%, Cryptococcus laurentti (1.7%, and Cryptococcus luteolus (1.7%. A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

  7. Flow cytometry susceptibility testing for conventional antifungal drugs and Comparison with the NCCLS Broth Macrodilution Test

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    M.J. Najafzadeh

    2009-08-01

    Full Text Available Introduction: During the last decade, the incidence of fungal infection has been increased in many countries. Because of the advent of resistant to antifungal agents, determination of an efficient strategic plan for treatment of fungal disease is an important issue in clinical mycology. Many methods have been introduced and developed for determination of invitro susceptibility tests. During the recent years, flow cytometry has developed to solving the problem and many papers have documented the usefulness of this technique. Materials and methods: As the first step, the invitro susceptibility of standard PTCC (Persian Type of Culture Collection strain and some clinical isolates of Candida consisting of Candida albicans, C. dubliniensis, C. glabrata, C. kefyer and C. parapsilosis were evaluated by macrodilution broth method according to NCCLS (National Committee for Clinical Laboratory Standards guidelines and flow cytometry susceptibility test. Results:  The data indicated that macro dilution broth methods and flow cytometry have the same results in determination of MIC (Minimum Inhibitory Concentration for amphotericin B, clotrimazole, fluconazole, ketoconazole and miconazole in C. albicans PTCC 5027 as well as clinical Candida isolates, such as C.albicans, C.dubliniensis, C.glabrata C.kefyr, and C.parapsilosis. Discussion: Comparing the results obtained by macrodilution broth and flow cytometry methods revealed that flow cytometry was faster. It is suggested that flow cytometry susceptibility test can be used as a powerful tool for determination of MIC and administration of the best antifungal drug in treatment of patients with Candida infections.

  8. Spectrophotometric and spectroscopic studies on charge transfer complexes of the antifungal drug clotrimazole

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    Nasrin Banu Shaikh Ismail

    2017-09-01

    Full Text Available Clotrimazole (CLZ is an imidazole derivative that is therapeutically used as an antifungal drug. The routine control analysis of CLZ requires rapid, reliable, accurate and precise methods for the quantification of the drug in its pharmaceutical formulations. Spectrophotometric methods are presented for the determination of the antifungal agent that are based on the charge transfer complexation reaction of CLZ with the π-acceptors tetracyanoethylene (TCE and 7,7′,8,8′-tetracyanoquinodimethane (TCNQ. The formation of coloured complexes was quantitated at 396 nm and 842 nm for CLZ-TCE and CLZ-TCNQ, respectively, which enabled the development of simple and accurate spectrophotometric methods for the analysis of CLZ in pure drug substances and its pharmaceutical products. Under the optimum reaction conditions, linear relationships with appreciable correlation coefficients (0.9985–0.9994 were found between the absorbance at the relevant maxima and the concentrations of CLZ in the range of 5.00–35.00 μg mL−1 for CLZ-TCE and 1.00–25.00 μg mL−1 for CLZ-TCNQ. The molar absorptivities and Sandell's sensitivity values were also statistically evaluated. The proposed methods were successfully applied to analyze CLZ in topical creams and sterile solutions with mean recovery percentages in the range of 99.60–100.20%, which indicated no interference from the inactive ingredients. Furthermore, the charge transfer complexes of CLZ were also characterized by FT-IR spectroscopy.

  9. Progressive development in experimental models of transungual drug delivery of anti-fungal agents.

    Science.gov (United States)

    Thatai, P; Tiwary, A K; Sapra, B

    2016-02-01

    Pre-clinical development comprises of different procedures that relate drug discovery in the laboratory for commencement of human clinical trials. Pre-clinical studies can be designed to recognize a lead candidate from a list to develop the procedure for scale-up, to choose the unsurpassed formulation, to determine the frequency, and duration of exposure; and eventually make the foundation of the anticipated clinical trial design. The foremost aim in the pharmaceutical research and industry is the claim of drug product quality throughout a drug's life cycle. The particulars of the pre-clinical development process for different candidates may vary; however, all have some common features. Typically in vitro, in vivo or ex vivo studies are elements of pre-clinical studies. Human pharmacokinetic in vivo studies are often supposed to serve as the 'gold standard' to assess product performance. On the other hand, when this general assumption is revisited, it appears that in vitro studies are occasionally better than in vivo studies in assessing dosage forms. The present review is compendious of different such models or approaches that can be used for designing and evaluation of formulations for nail delivery with special reference to anti-fungal agents. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  10. Lemon grass (Cymbopogon citratus essential oil as a potent anti-inflammatory and antifungal drugs

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    Mohamed Nadjib Boukhatem

    2014-09-01

    Full Text Available Background: Volatile oils obtained from lemon grass [Cymbopogon citratus (DC. Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims: In the present study, lemon grass essential oil (LGEO was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods: The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%, and neral (31.5%. The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results: LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs (35–90 mm. IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg, which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion: Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for

  11. Triazole derivatives with improved in vitro antifungal activity over azole drugs

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    Yu S

    2014-04-01

    Full Text Available Shichong Yu,1,* Xiaoyun Chai,1,* Yanwei Wang,1 Yongbing Cao,2 Jun Zhang,3 Qiuye Wu,1 Dazhi Zhang,1 Yuanying Jiang,2 Tianhua Yan,4 Qingyan Sun11Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 3Overseas Education Faculty of the Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: A series of triazole antifungal agents with piperidine side chains was designed and synthesized. The results of antifungal tests against eight human pathogenic fungi in vitro showed that all the compounds exhibited moderate-to-excellent activities. Molecular docking between 8d and the active site of Candida albicans CYP51 was provided based on the computational docking results. The triazole interacts with the iron of the heme group. The difluorophenyl group is located in the S3 subsite and its fluorine atom (2-F can form H-bonds with Gly307. The side chain is oriented into the S4 subsite and formed hydrophobic and van der Waals interactions with the amino residues. Moreover, the phenyl group in the side chain interacts with the phenol group of Phe380 through the formation of π–π face-to-edge interactions.Keywords: synthesis, CYP51, molecular docking, azole agents

  12. Antagonistic changes in sensitivity to antifungal drugs by mutations of an important ABC transporter gene in a fungal pathogen.

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    Wenjun Guan

    2010-06-01

    Full Text Available Fungal pathogens can be lethal, especially among immunocompromised populations, such as patients with AIDS and recipients of tissue transplantation or chemotherapy. Prolonged usage of antifungal reagents can lead to drug resistance and treatment failure. Understanding mechanisms that underlie drug resistance by pathogenic microorganisms is thus vital for dealing with this emerging issue. In this study, we show that dramatic sequence changes in PDR5, an ABC (ATP-binding cassette efflux transporter protein gene in an opportunistic fungal pathogen, caused the organism to become hypersensitive to azole, a widely used antifungal drug. Surprisingly, the same mutations conferred growth advantages to the organism on polyenes, which are also commonly used antimycotics. Our results indicate that Pdr5p might be important for ergosterol homeostasis. The observed remarkable sequence divergence in the PDR5 gene in yeast strain YJM789 may represent an interesting case of adaptive loss of gene function with significant clinical implications.

  13. Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients.

    Science.gov (United States)

    Andes, David; Azie, Nkechi; Yang, Hongbo; Harrington, Rachel; Kelley, Caroline; Tan, Ruo-Ding; Wu, Eric Q; Franks, Billy; Kristy, Rita; Lee, Edward; Khandelwal, Nikhil; Spalding, James

    2016-06-01

    The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the

  14. Solvates of the antifungal drug griseofulvin: structural, thermochemical and conformational analysis.

    Science.gov (United States)

    Aitipamula, Srinivasulu; Chow, Pui Shan; Tan, Reginald B H

    2014-02-01

    Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the solvates were characterized by differential scanning calorimetry, thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The solvents that form the solvates are acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all the solvates lose the solvent molecules from the crystal lattice between 343 and 383 K, and that the melting point of the desolvated materials matched the melting point of the solvent-free GF (493 K). The conformation of the GF molecule in solvent-free form was found to be significantly different from the conformations found in the solvates. Solution stability studies revealed that the GF-acetonitrile solvate transforms to GF and that GF-nitroethane (1:1) solvate transforms to GF-nitroethane (2:1) solvate. On the other hand, GF-nitromethane and GF-nitroethane (2:1) solvates were found to be stable in solution. Our results highlight the importance of the co-crystallization technique in the pharmaceutical drug development; it not only expands the solid form diversity but also creates new avenues for unraveling novel solvates.

  15. Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria infectoria in a Heart Transplant Recipient.

    Science.gov (United States)

    Lyskova, Pavlina; Kubanek, Milos; Hubka, Vit; Sticova, Eva; Voska, Ludek; Kautznerova, Dana; Kolarik, Miroslav; Hamal, Petr; Vasakova, Martina

    2017-04-01

    We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61-year-old heart transplant recipient with multiple skin lesions and pulmonary infiltrates. The infection spread via the haematogenous route from the primary cutaneous lesions into the lungs. The diagnosis was based on the histopathological examination, direct microscopy, skin lesion cultures and detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular methods. The treatment consisted of a combination of surgical excision and systemic antifungal therapy. Voriconazole was the first agent used but had a weak effect. Posaconazole was subsequently used to achieve a successful response. The isolate was identified as A. infectoria by sequencing of the rDNA ITS region and the partial β-tubulin gene.

  16. Antifungal susceptibility of clinical and environmental isolates of Cryptococcus neoformans to four antifungal drugs determined by two techniques.

    Science.gov (United States)

    Moraes, E M P; Prímola, N S; Hamdan, Júnia Soares

    2003-06-01

    A total of 64 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates var. neoformans and var. gattii, were tested for susceptibility to amphotericin B, 5-flucytosine, fluconazole and itraconazole. The tests were performed according to the recommendations of National Committee of Clinical Laboratory Standards and the method of macrodilution in liquid medium of Shadomy et al. [Manual de Microbiologia Clínica, 4th ed. Buenos Aires: Editorial Medica Panamericana, 1987: 1229-38]. For most drugs there was a significant difference between the readings taken at 24 and 48 h with both methods. When the minimum inhibitory concentrations obtained by the two techniques were compared, significant differences were observed for amphotericin B and fluconazole. Overall, differences in drug susceptibility with respect to the origin of the isolates or the variety of the fungus were not observed. As an exception, the gattii variety exhibited a high resistance rate to amphotericin B when the technique of Shadomy et al. was applied, a fact possibly related to the greater difficulty for treatment of the disease caused by this fungal variety.

  17. Antifungal susceptibility of invasive yeast isolates in Italy: the GISIA3 study in critically ill patients

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    Mussap Michele

    2011-05-01

    Full Text Available Abstract Background Yeasts are a common cause of invasive fungal infections in critically ill patients. Antifungal susceptibility testing results of clinically significant fungal strains are of interest to physicians, enabling them to adopt appropriate strategies for empiric and prophylactic therapies. We investigated the antifungal susceptibility of yeasts isolated over a 2-year period from hospitalised patients with invasive yeast infections. Methods 638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC and two co-ordinating centres (CC. The Clinical and Laboratory Standards Institute (CLSI reference broth microdilution method was used at the CCs for comparison. Results Etest and Sensititre (LC/CC MIC90 values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC90 values were influenced by the reduced susceptibility of Candida parapsilosis isolates to echinocandins and a reduced or lack of susceptibility of Candida glabrata and Candida krusei to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre, and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre; differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected. Conclusions Our data confirm the different antifungal susceptibility

  18. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia

    DEFF Research Database (Denmark)

    Arendrup, M C; Dzajic, E; Jensen, R H

    2013-01-01

    .7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were...

  19. Comparison of the In Vitro Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum

    NARCIS (Netherlands)

    Deng, S.; Zhang, C.; Seyedmousavi, S.; Zhu, S.; Tan, X.; Wen, Y.; Huang, X.; Lei, W.; Zhou, Z.; Fang, W.; Shen, S.; Deng, D.; Pan, W.; Liao, W.

    2015-01-01

    One hundred eleven clinical Trichophyton rubrum isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26

  20. Measurement and correlation of antifungal drugs solubility in pure supercritical CO{sub 2} using semiempirical models

    Energy Technology Data Exchange (ETDEWEB)

    Yamini, Yadollah, E-mail: yyamini@modares.ac.ir [Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of); Moradi, Morteza [Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of)

    2011-07-15

    Highlights: > Ketoconazole (KZ) and clotrimazole (CZ) are two antifungal drugs. > The solubilities of KZ and CZ were measured in supercritical CO{sub 2}. > The experimental results were correlated using five density based models. > The heats' of drug-CO{sub 2} solvation and drug vaporization were estimated. - Abstract: In the present study the solubilities of two antifungal drugs of ketoconazole and clotrimazole in supercritical carbon dioxide were measured using a simple static method. The experimental data were measured at (308 to 348) K, over the pressure range of (12.2 to 35.5) MPa. The mole fraction solubilities ranged from 0.2 . 10{sup -6} to 17.45 . 10{sup -5}. In this study five density based models were used to calculate the solubility of drugs in supercritical carbon dioxide. The density based models are Chrastil, modified Chrastil, Bartle, modified Bartle and Mendez-Santiago and Teja (M-T). Interaction parameters for the studied models were obtained and the percentage of average absolute relative deviation (AARD%) in each calculation was displayed. The correlation results showed good agreement with the experimental data. A comparison among the five models revealed that the Bartle and its modified models gave much better correlations of the solubility data with an average absolute relative deviation (AARD%) ranging from 4.8% to 6.2% and from 4.5% to 6.3% for ketoconazole and clotrimazole, respectively. Using the correlation results, the heat of drug-CO{sub 2} solvation and that of drug vaporization was separately approximated in the range of (-22.1 to -26.4 and 88.3 to 125.9) kJ . mol{sup -1}.

  1. The In Vitro Efficacy of Essential Oils and Antifungal Drugs Against Prototheca zopfii.

    Science.gov (United States)

    Grzesiak, Barbara; Głowacka, Anna; Krukowski, Henryk; Lisowski, Andrzej; Lassa, Henryka; Sienkiewicz, Monika

    2016-08-01

    The algae of the genus Prototheca are environmental pathogens whose main reservoir is the habitat of cows. They can cause protothecosis in domestic and wild animals, as well as human beings, with the main etiological agents being Prototheca zopfii in animals and Prototheca wickerhamii in humans. The aim of the study was to evaluate the in vitro activity of selected essential oils and antifungal antibiotics against P. zopfii isolates. The material consisted of nine P. zopfii strains isolated from the milk of cows suffering from mastitis. Eight essential oils produced by POLLENA-AROMA, Poland, and nine antifungal agents were tested. The effects of essential oils on P. zopfii were evaluated by microdilution with liquid Sabouraud dextrose broth, and susceptibility to antifungal agents was tested using the disk-diffusion method. All used essential oils inhibited the activity of P. zopfii isolates, with MIC values ranging from 0.2 to 10.5 μl/ml. Cinnamon, clove, and thyme demonstrated the highest activity against the tested P. zopfii strains at concentrations ranging from 0.6 to 1.0 μl/ml. Of the antifungal agents, the tested strains were the most sensitive to nystatin (100 %). The tested essential oils can be used to complement protothecosis therapy in animals and human beings.

  2. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

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    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  3. Mitochondrial respiratory pathways inhibition in Rhizopus oryzae potentiates activity of posaconazole and itraconazole via apoptosis.

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    Fazal Shirazi

    Full Text Available The incidence of mucormycosis has increased drastically in immunocompromised patients. Also the array of targets whose inhibition results in Mucorales death is limited. Recently, researchers identified mitochondria as important regulators of detoxification and virulence mechanisms in fungi. In this context, targeting the mitochondrial respiratory chain may provide a new platform for antifungal development. We hypothesized that targeting respiratory pathways potentiates triazoles activity via apoptosis. We found that simultaneous administration of antimycin A (AA and benzohydroxamate (BHAM, inhibitors of classical and alternative mitochondrial pathways respectively, resulted in potent activity of posaconazole (PCZ and itraconazole (ICZ against Rhizopus oryzae. We observed cellular changes characteristic of apoptosis in R. oryzae cells treated with PCZ or ICZ in combination with AA and BHAM. The fungicidal activity of this combination against R. oryzae was correlated with intracellular reactive oxygen species accumulation (ROS, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased caspase like activity. DNA fragmentation and condensation assays also revealed apoptosis of R. oryzae cells. These apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine. Taken together, these findings suggest that the use of PCZ or ICZ in combination with AA and BHAM makes R. oryzae exquisitely sensitive to treatment with triazoles via apoptosis. This strategy may serve as a new model for the development of improved or novel antifungal agents.

  4. Mitochondrial Respiratory Pathways Inhibition in Rhizopus oryzae Potentiates Activity of Posaconazole and Itraconazole via Apoptosis

    Science.gov (United States)

    Shirazi, Fazal; Kontoyiannis, Dimitrios P.

    2013-01-01

    The incidence of mucormycosis has increased drastically in immunocompromised patients. Also the array of targets whose inhibition results in Mucorales death is limited. Recently, researchers identified mitochondria as important regulators of detoxification and virulence mechanisms in fungi. In this context, targeting the mitochondrial respiratory chain may provide a new platform for antifungal development. We hypothesized that targeting respiratory pathways potentiates triazoles activity via apoptosis. We found that simultaneous administration of antimycin A (AA) and benzohydroxamate (BHAM), inhibitors of classical and alternative mitochondrial pathways respectively, resulted in potent activity of posaconazole (PCZ) and itraconazole (ICZ) against Rhizopus oryzae. We observed cellular changes characteristic of apoptosis in R. oryzae cells treated with PCZ or ICZ in combination with AA and BHAM. The fungicidal activity of this combination against R. oryzae was correlated with intracellular reactive oxygen species accumulation (ROS), phosphatidylserine externalization, mitochondrial membrane depolarization, and increased caspase like activity. DNA fragmentation and condensation assays also revealed apoptosis of R. oryzae cells. These apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine. Taken together, these findings suggest that the use of PCZ or ICZ in combination with AA and BHAM makes R. oryzae exquisitely sensitive to treatment with triazoles via apoptosis. This strategy may serve as a new model for the development of improved or novel antifungal agents. PMID:23696824

  5. The dual role of candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance

    Science.gov (United States)

    Costa, Catarina; Henriques, André; Pires, Carla; Nunes, Joana; Ohno, Michiyo; Chibana, Hiroji; Sá-Correia, Isabel; Teixeira, Miguel C.

    2013-01-01

    Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms. In this study, the drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g), from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a green fluorescent protein fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of 3H-flucytosine and, to a moderate extent, of 3H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of 14C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization and

  6. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans.

    Science.gov (United States)

    Humphrey, M J; Jevons, S; Tarbit, M H

    1985-11-01

    The pharmacokinetic profile of UK-49,858 (fluconazole), a novel triazole antifungal agent which is being developed for oral and intravenous use, was determined in mice, rats, dogs, and humans. Comparative data following oral and intravenous administration showed that bioavailability was essentially complete in all four species. Peak concentrations in plasma of drug normalized to a 1-mg/kg dose level following oral administration, were relatively high: 0.7, 0.6, 1.1, and 1.4 micrograms/ml in mice, rats, dogs, and humans, respectively. The volumes of distribution ranged between 1.1 liter/kg in mice and 0.7 liter/kg in humans, which are approximate to the values for total body water. Whole body autoradiography studies in mice following intravenous administration of [14C]UK-49,858 demonstrated that the drug was evenly distributed throughout the tissues, including the central nervous system and the gastrointestinal tract. Plasma protein binding was low (11 to 12%) in all species. Marked species differences were observed in elimination half-lives, with mean values of 4.8, 4.0, 14, and 22 h in mice, rats, dogs, and humans, respectively. The major route of elimination of the drug was renal clearance, with about 70% of the dose being excreted unchanged in the urine in each species. Studies with [14C]UK-49,858 on metabolism and excretion (intravenous and oral) in mice and dogs showed that about 90% of the dose was recovered as unchanged drug in urine and feces, confirming the metabolic stability of the drug. This pharmacokinetic profile is markedly different from that of imidazole antifungal drugs and undoubtedly contributes to the excellent efficacy of UK-49,858 in vivo.

  7. In vitro antifungal susceptibility of Malassezia furfur from bloodstream infections.

    Science.gov (United States)

    Iatta, Roberta; Figueredo, Luciana A; Montagna, Maria Teresa; Otranto, Domenico; Cafarchia, Claudia

    2014-11-01

    Fungaemia caused by Malassezia spp. in hospitalized patients requires prompt and appropriate therapy, but standard methods for the definition of the in vitro antifungal susceptibility have not been established yet. In this study, the in vitro susceptibility of Malassezia furfur from bloodstream infections (BSIs) to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VRC) was assessed using the broth microdilution (BMD) method of the Clinical and Laboratory Standards Institute (CLSI) with different media such as modified Sabouraud dextrose broth (SDB), RPMI and Christensen's urea broth (CUB). Optimal broth media that allow sufficient growth of M. furfur, and produce reliable and reproducible MICs using the CLSI BMD protocol were assessed. Thirty-six M. furfur isolates collected from BSIs of patients before and during AMB therapy, and receiving FLC prophylaxis, were tested. A good growth of M. furfur was observed in RPMI, CUB and SDB at 32 °C for 48 and 72 h. No statistically significant differences were detected between the MIC values registered after 48 and 72 h incubation. ITC, POS and VRC displayed lower MICs than FLC and AMB. These last two antifungal drugs showed higher and lower MICs, respectively, when the isolates were tested in SDB. SDB is the only medium in which it is possible to detect isolates with high FLC MICs in patients receiving FLC prophylaxis. A large number of isolates showed high AMB MIC values regardless of the media used. In conclusion, SDB might be suitable to determine triazole susceptibility. However, the media, the drug formulation or the breakpoints herein applied might not be useful for assessing the AMB susceptibility of M. furfur from BSIs. © 2014 The Authors.

  8. A Young, Immunocompetent Woman with Small Bowel and Hepatic Mucormycosis Successfully Treated with Aggressive Surgical Debridements and Antifungal Therapy

    Directory of Open Access Journals (Sweden)

    Daniel Vikum

    2017-01-01

    Full Text Available A 24-year-old woman with coeliac disease and transient neutropenia developed mucormycosis with extensive involvement of the liver and small intestine. She was successfully treated with aggressive surgical debridements and long-term antifungal therapy with liposomal amphotericin B and posaconazole.

  9. Antifungal Susceptibility Testing of Malassezia spp. with an Optimized Colorimetric Broth Microdilution Method.

    Science.gov (United States)

    Leong, Cheryl; Buttafuoco, Antonino; Glatz, Martin; Bosshard, Philipp P

    2017-06-01

    Malassezia is a genus of lipid-dependent yeasts. It is associated with common skin diseases such as pityriasis versicolor and atopic dermatitis and can cause systemic infections in immunocompromised individuals. Owing to the slow growth and lipid requirements of these fastidious yeasts, convenient and reliable antifungal drug susceptibility testing assays for Malassezia spp. are not widely available. Therefore, we optimized a broth microdilution assay for the testing of Malassezia that is based on the CLSI and EUCAST assays for Candida and other yeasts. The addition of ingredients such as lipids and esculin provided a broth medium formulation that enabled the growth of all Malassezia spp. and could be read, with the colorimetric indicator resazurin, by visual and fluorescence readings. We tested the susceptibility of 52 strains of 13 Malassezia species to 11 commonly used antifungals. MIC values determined by visual readings were in good agreement with MIC values determined by fluorescence readings. The lowest MICs were found for the azoles itraconazole, posaconazole, and voriconazole, with MIC 90 values of 0.03 to 1.0 μg/ml, 0.06 to 0.5 μg/ml, and 0.03 to 2.0 μg/ml, respectively. All Malassezia spp. were resistant to echinocandins and griseofulvin. Some Malassezia spp. also showed high MIC values for ketoconazole, which is the most widely recommended topical antifungal to treat Malassezia skin infections. In summary, our assay enables the fast and reliable susceptibility testing of Malassezia spp. with a large panel of different antifungals. Copyright © 2017 American Society for Microbiology.

  10. Requirement for ergosterol in V-ATPase function underlies antifungal activity of azole drugs.

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    Yong-Qiang Zhang

    2010-06-01

    Full Text Available Ergosterol is an important constituent of fungal membranes. Azoles inhibit ergosterol biosynthesis, although the cellular basis for their antifungal activity is not understood. We used multiple approaches to demonstrate a critical requirement for ergosterol in vacuolar H(+-ATPase function, which is known to be essential for fungal virulence. Ergosterol biosynthesis mutants of S. cerevisiae failed to acidify the vacuole and exhibited multiple vma(- phenotypes. Extraction of ergosterol from vacuolar membranes also inactivated V-ATPase without disrupting membrane association of its subdomains. In both S. cerevisiae and the fungal pathogen C. albicans, fluconazole impaired vacuolar acidification, whereas concomitant ergosterol feeding restored V-ATPase function and cell growth. Furthermore, fluconazole exacerbated cytosolic Ca(2+ and H(+ surges triggered by the antimicrobial agent amiodarone, and impaired Ca(2+ sequestration in purified vacuolar vesicles. These findings provide a mechanistic basis for the synergy between azoles and amiodarone observed in vitro. Moreover, we show the clinical potential of this synergy in treatment of systemic fungal infections using a murine model of Candidiasis. In summary, we demonstrate a new regulatory component in fungal V-ATPase function, a novel role for ergosterol in vacuolar ion homeostasis, a plausible cellular mechanism for azole toxicity in fungi, and preliminary in vivo evidence for synergism between two antifungal agents. New insights into the cellular basis of azole toxicity in fungi may broaden therapeutic regimens for patient populations afflicted with systemic fungal infections.

  11. Ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet for determination of three antifungal drugs in water and biological samples.

    Science.gov (United States)

    Ezoddin, Maryam; Shojaie, Mehran; Abdi, Khosrou; Karimi, Mohammad Ali

    2017-03-01

    A novel ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet (UAAD-LLM-SFO) followed by HPLC-UV detection was developed for the analysis of three antifungal drugs in water and biological samples. In this method, 1-dodecanol was used as the extraction solvent. The emulsion was rapidly formed by pulling in and pushing out the mixture of sample solution and extraction solvent for 5 times repeatedly using a 10-mL glass syringe while sonication was performed. Therefore, an organic dispersive solvent required in common microextraction methods was not used in the proposed method. After dispersing, an aliquot of acetonitrile was introduced as a demulsifier solvent into the sample solution to separate two phases. Therefore, some additional steps, such as the centrifugation, ultrasonication, or agitation of the sample solution, are not needed. Parameters influencing the extraction recovery were investigated. The proposed method showed a good linearity for the three antifungal drugs studied with the correlation coefficients (R 2  > 0.9995). The limits of detection (LODs) and the limits of the quantification (LOQs) were between 0.01-0.03 μg L -1 and 0.03-0.08 μg L -1 , respectively. The preconcentration factors (PFs) were in the range of 107-116, respectively. The precisions, as the relative standard deviations (RSDs) (n = 5), for inter-day and intra-day analysis were in the range of 2.1-4.5% and 6.5-8.5%, respectively. This method was successfully applied to determine the three antifungal drugs in tap water and biological samples. The recoveries of antifungal drugs in these samples were 92.4-98.5%. Graphical abstract Ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet for the analysis of three antifungal drugs prior HPLC-UV.

  12. Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications

    DEFF Research Database (Denmark)

    Dzieciuch-Rojek, Monika; Poojari, Chetan; Bednar, Jan

    2017-01-01

    Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore...... of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film...... to its protective properties, PEGylation significantly increases the stability of liposomes that host ITZ. In a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer without PEGylation, ITZ was found to reside inside the lipid bilayer between the glycerol and the double-bond regions of POPC...

  13. In vitro susceptibility of antifungal drugs against Sporothrix brasiliensis recovered from cats with sporotrichosis in Brazil.

    Science.gov (United States)

    Brilhante, Raimunda Sâmia Nogueira; Rodrigues, Anderson Messias; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha; Pereira, Sandro Antonio; Gremião, Isabella Dib Ferreira; Schubach, Tânia Maria Pacheco; de Camargo, Zoilo Pires

    2016-03-01

    Sporotrichosis is an important subcutaneous mycosis of humans and animals. Classically, the disease is acquired upon traumatic inoculation of Sporothrix propagules from contaminated soil and plant debris. In addition, the direct horizontal transmission of Sporothrix among animals and the resulting zoonotic infection in humans highlight an alternative and efficient rout of transmission through biting and scratching. Sporothrix brasiliensis is the most virulent species of the Sporothrix schenckii complex and is responsible for the long-lasting outbreak of feline sporotrichosis in Brazil. However, antifungal susceptibility data of animal-borne isolates is scarce. Therefore, this study evaluated the in vitro activity of amphotericin B, caspofungin, itraconazole, voriconazole, fluconazole, and ketoconazole against animal-borne isolates of S. brasiliensis. The susceptibility tests were performed through broth microdilution (M38-A2). The results show the relevant activity of itraconazole, amphotericin B, and ketoconazole against S. brasiliensis, with the following MIC ranges: 0.125-2, 0.125-4 and 0.0312-2 μg/ml, respectively. Caspofungin was moderately effective, displaying higher variation in MIC values (0.25-64 μg/ml). Voriconazole (2-64 μg/ml) and fluconazole (62.5-500 μg/ml) showed low activity against S. brasiliensis strains. This study contributed to the characterization of the in vitro antifungal susceptibility of strains of S. brasiliensis recovered from cats with sporotrichosis, which have recently been considered the main source of human infections. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

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    Grau Santiago

    2012-04-01

    Full Text Available Abstract Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole for the prevention of invasive fungal infections (IFI and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML or myelodysplastic syndromes (MDS. The perspective was that of the Spanish National Health Service (NHS. Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS, total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11, increased LYS (2.52 versus 2.43, and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928 per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy compared with fluconazole or itraconazole in high-risk neutropenic patients.

  15. Hyperthermia sensitizes Rhizopus oryzae to posaconazole and itraconazole action through apoptosis.

    Science.gov (United States)

    Shirazi, Fazal; Pontikos, Michael A; Walsh, Thomas J; Albert, Nathaniel; Lewis, Russell E; Kontoyiannis, Dimitrios P

    2013-09-01

    The high mortality rate of mucormycosis with currently available monotherapy has created interest in studying novel strategies for antifungal agents. With the exception of amphotericin B (AMB), the triazoles (posaconazole [PCZ] and itraconazole [ICZ]) are fungistatic in vitro against Rhizopus oryzae . We hypothesized that growth at a high temperature (42°C) results in fungicidal activity of PCZ and ICZ that is mediated through apoptosis. R. oryzae had high MIC values for PCZ and ICZ (16 to 64 μg/ml) at 25°C; in contrast, the MICs for PCZ and ICZ were significantly lower at 37°C (8 to 16 μg/ml) and 42°C (0.25 to 1 μg/ml). Furthermore, PCZ and ICZ dose-dependent inhibition of germination was more pronounced at 42°C than at 37°C. In addition, intracellular reactive oxygen species (ROS) increased significantly when fungi were exposed to antifungals at 42°C. Characteristic cellular changes of apoptosis in R. oryzae were induced by the accumulation of intracellular reactive oxygen species. Cells treated with PCZ or ICZ in combination with hyperthermia (42°C) exhibited characteristic markers of early apoptosis: phosphatidylserine externalization visualized by annexin V staining, membrane depolarization visualized by bis-[1,3-dibutylbarbituric acid] trimethine oxonol (DiBAC) staining, and increased metacaspase activity. Moreover, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and DAPI (4',6-diamidino-2-phenylindole) staining demonstrated DNA fragmentation and condensation, respectively. The addition of N-acetylcysteine increased fungal survival, prevented apoptosis, reduced ROS accumulation, and decreased metacaspase activation. We concluded that hyperthermia, either alone or in the presence of PCZ or ICZ, induces apoptosis in R. oryzae. Local thermal delivery could be a therapeutically useful adjunct strategy for these refractory infections.

  16. Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

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    David Quinto-Alemany

    Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

  17. Comparative study on the effects of two antifungal drugs against Candida albicans by microcalorimetry and transmission electron microscopy

    International Nuclear Information System (INIS)

    Guo, Qing-Lian; Zhang, Juan; Xu, Zi-Qiang; Li, Ran; Jiang, Feng-Lei; Xiao, Qi; Liu, Yi

    2012-01-01

    Highlights: ► Microcalorimetry is a fast, simple method to study the antibiotic property of drugs. ► We noticed that the antibiotic effect of ITZ was slightly better than that of KTZ. ► We perform the TEM to study the morphology changes of C. albicans cells. - Abstract: In this work, a multi-channel thermal activity monitor (TAM 2277) was applied to study the growth metabolism of Candida albicans (C. albicans) in vitro in the absence and presence of different concentrations of ketoconazole (KTZ) and itraconazole (ITZ). The results showed that the half inhibiting concentrations (IC 50 ) of C. albicans by KTZ and ITZ are 73.5 and 66.3 μmol L −1 , respectively. So the antibiotic effect of ITZ was slightly better than that of KTZ. The morphology of C. albicans cells both in the absence and presence of antifungal agents was examined by transmission electron microscopy (TEM). Our research also suggests that microcalorimetry is a fast, simple, non-invasive, non-destructive and more sensitive method, and can be easily performed to study the antibiotic property of different species of drugs on microorganism compared to other biological and clinical methods.

  18. Comparative study on the effects of two antifungal drugs against Candida albicans by microcalorimetry and transmission electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Qing-Lian [Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Zhang, Juan [Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Department of Stomatology, Hubei Provincial Maternal and Child Health Hospital, Wuhan 430070 (China); Xu, Zi-Qiang; Li, Ran [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Jiang, Feng-Lei, E-mail: fljiang@whu.edu.cn [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Xiao, Qi, E-mail: qi.xiao@whu.edu.cn [College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001 (China); Liu, Yi [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China)

    2012-09-10

    Highlights: Black-Right-Pointing-Pointer Microcalorimetry is a fast, simple method to study the antibiotic property of drugs. Black-Right-Pointing-Pointer We noticed that the antibiotic effect of ITZ was slightly better than that of KTZ. Black-Right-Pointing-Pointer We perform the TEM to study the morphology changes of C. albicans cells. - Abstract: In this work, a multi-channel thermal activity monitor (TAM 2277) was applied to study the growth metabolism of Candida albicans (C. albicans) in vitro in the absence and presence of different concentrations of ketoconazole (KTZ) and itraconazole (ITZ). The results showed that the half inhibiting concentrations (IC{sub 50}) of C. albicans by KTZ and ITZ are 73.5 and 66.3 {mu}mol L{sup -1}, respectively. So the antibiotic effect of ITZ was slightly better than that of KTZ. The morphology of C. albicans cells both in the absence and presence of antifungal agents was examined by transmission electron microscopy (TEM). Our research also suggests that microcalorimetry is a fast, simple, non-invasive, non-destructive and more sensitive method, and can be easily performed to study the antibiotic property of different species of drugs on microorganism compared to other biological and clinical methods.

  19. Molecular Basis for Enhanced Activity of Posaconazole against Absidia corymbifera and Rhizopus oryzae▿

    Science.gov (United States)

    Chau, Andrew S.; Chen, Guodong; McNicholas, Paul M.; Mann, Paul A.

    2006-01-01

    Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from Absidia corymbifera and Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased resistance to fluconazole and voriconazole but not to posaconazole and itraconazole. PMID:16966400

  20. Efficient click chemistry towards fatty acids containing 1,2,3-triazole: Design and synthesis as potential antifungal drugs for Candida albicans.

    Science.gov (United States)

    Fu, Nina; Wang, Suiliang; Zhang, Yuqian; Zhang, Caixia; Yang, Dongliang; Weng, Lixing; Zhao, Baomin; Wang, Lianhui

    2017-08-18

    Candida is an important opportunistic human fungal pathogen. The cis-2-dodecenoic acid (BDSF) showing in vitro activity of against C. albicans growth, germ-tube germination and biofilm formation has been a potential inhibitor for Candida and other fungi. In this study, facile synthetic strategies toward a novel family of BDSF analogue, 1-alkyl-1H-1,2,3-triazole-4-carboxylic acids (ATCs) was developed. The straightforward synthetic method including converting the commercial available alkyl bromide to alkyl azide, consequently with a typical click chemistry method, copper(II) sulfate and sodium ascorbate as catalyst in water to furnish ATCs with mild to good yields. According to antifungal assay, 1-decyl-4,5-dihydro-1H-1,2,3-triazole-4-carboxylic acid (5d) showed antifungal capability slightly better than BDSF. The 1,2,3-triazole unit played a crucial role for the bioactivity of ATCs was also confirmed when compared with two alkyl-aromatic carboxylic acids. Given its simplicity, high antifungal activity, and wide availability of compounds with halide atoms on the end part of the alkyl chains, the method can be extended to develop more excellent ATC drugs for accomplishing the challenges in future antifungal applications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species.

    Science.gov (United States)

    Hsu, Li-Hang; Wang, Hsuan-Fu; Sun, Pei-Lun; Hu, Fung-Rong; Chen, Ying-Lien

    2017-06-01

    The genus Fusarium comprises many species, including Fusarium oxysporum, Fusarium solani, Fusarium graminearum and Fusarium verticillioides, and causes severe infections in plants and humans. In clinical settings, Fusarium is the third most frequent mould to cause invasive fungal infections after Aspergillus and the Mucorales. F. solani and F. oxysporum are the most prevalent Fusarium spp. causing clinical disease. However, few effective antifungal drugs are available to treat human and plant Fusarium infections. The cationic peptide antibiotic polymyxin B (PMB) exhibits antifungal activity against the human fungal pathogens Candida albicans and Cryptococcus neoformans, but its efficacy against Fusarium spp. is unknown. In this study, the antifungal activity of PMB was tested against 12 Fusarium strains that infect humans and plants (banana, tomato, melon, pea, wheat and maize). PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 µg/mL or 64 µg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. PMB exhibits synergistic activity with posaconazole and can potentiate the effect of fluconazole, voriconazole or amphotericin B against Fusarium spp. However, PMB does not show synergistic effects with fluconazole against Fusarium spp. as it does against Candida glabrata and C. neoformans, indicating evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats.

    Science.gov (United States)

    Han, Hock Siew; Kano, Rui; Chen, Charles; Noli, Chiara

    2017-02-01

    Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown. To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy. Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months. Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy. The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility. © 2017 ESVD and ACVD.

  3. Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Mônica Pereira Garcia

    2013-12-01

    Full Text Available The use of magnetic nanoparticles (MNPs in drug delivery vehicles must address issues such as drugloading capacity, desired release profile, aqueous dispersion stability, biocompatibility with cells and tissue, and retention of magnetic properties after interaction with macromolecules or modification via chemical reactions. Amphotericin B (AmB is still the first choice for the treatment of severe paracoccidioidomycosis, an important systemic fungal infection caused by Paracoccidoides brasiliensis. Unfortunately, AmB causes acute side effects (mainly urinary problems following intravenous administration, which limits its clinical use. The use of magnetic nanoparticles stabilized with biocompatible substances, together with the possibility of their conjugation with drugs has become a new nanotechnological strategy in the treatment of diseases for drug delivery to specific locations, such as the lungs in paracoccidoidiodomycosis. This review provides an overview of the disease, its etiologic agent and treatment with emphasis on the main strategies to improve the use of AmB in nanoformulations.

  4. Structure-activity relationships among antifungal nylon-3 polymers: identification of materials active against drug-resistant strains of Candida albicans.

    Science.gov (United States)

    Liu, Runhui; Chen, Xinyu; Falk, Shaun P; Mowery, Brendan P; Karlsson, Amy J; Weisblum, Bernard; Palecek, Sean P; Masters, Kristyn S; Gellman, Samuel H

    2014-03-19

    Fungal infections are a major challenge to human health that is heightened by pathogen resistance to current therapeutic agents. Previously, we were inspired by host-defense peptides to develop nylon-3 polymers (poly-β-peptides) that are toxic toward the fungal pathogen Candida albicans but exert little effect on mammalian cells. Based on subsequent analysis of structure-activity relationships among antifungal nylon-3 polymers, we have now identified readily prepared cationic homopolymers active against strains of C. albicans that are resistant to the antifungal drugs fluconazole and amphotericin B. These nylon-3 polymers are nonhemolytic. In addition, we have identified cationic-hydrophobic copolymers that are highly active against a second fungal pathogen, Cryptococcus neoformans, and moderately active against a third pathogen, Aspergillus fumigatus.

  5. Structure–Activity Relationships among Antifungal Nylon-3 Polymers: Identification of Materials Active against Drug-Resistant Strains of Candida albicans

    Science.gov (United States)

    2015-01-01

    Fungal infections are a major challenge to human health that is heightened by pathogen resistance to current therapeutic agents. Previously, we were inspired by host-defense peptides to develop nylon-3 polymers (poly-β-peptides) that are toxic toward the fungal pathogen Candida albicans but exert little effect on mammalian cells. Based on subsequent analysis of structure–activity relationships among antifungal nylon-3 polymers, we have now identified readily prepared cationic homopolymers active against strains of C. albicans that are resistant to the antifungal drugs fluconazole and amphotericin B. These nylon-3 polymers are nonhemolytic. In addition, we have identified cationic–hydrophobic copolymers that are highly active against a second fungal pathogen, Cryptococcus neoformans, and moderately active against a third pathogen, Aspergillus fumigatus. PMID:24606327

  6. Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp.

    Science.gov (United States)

    Gao, Lujuan; Jiang, Shaojie; Sun, Yi; Deng, Meiqi; Wu, Qingzhi; Li, Ming; Zeng, Tongxiang

    2016-01-01

    Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm(2)), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in

  7. FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action inMalassezia.

    Science.gov (United States)

    Ianiri, Giuseppe; Applen Clancey, Shelly; Lee, Soo Chan; Heitman, Joseph

    2017-10-24

    has adverse side effects and is not recommended for long treatment periods. Calcineurin inhibitors have been proposed as a suitable alternative to treat patients affected by skin lesions caused by Malassezia Although calcineurin inhibitors are well-known as immunosuppressive drugs, they are also characterized by potent antimicrobial activity. In the present study, we investigated the mechanism of action of FK506 (tacrolimus), ascomycin (FK520), and pimecrolimus in M. furfur and M. sympodialis and found that the conserved immunophilin FKBP12 is the target of these drugs with which it forms a complex that directly binds calcineurin and inhibits its signaling activity. We found that FKBP12 is also required for the additive activity of calcineurin inhibitors with fluconazole. Furthermore, the increasing natural occurrence in fungal pathogen populations of mutator strains poses a high risk for the rapid emergence of drug resistance and adaptation to host defense. This led us to generate an engineered hypermutator msh2 Δ mutant strain of M. sympodialis and genetically evaluate mutational events resulting in a substantially increased rate of resistance to FK506 compared to that of the wild type. Our study paves the way for the novel clinical use of calcineurin inhibitors with lower immunosuppressive activity that could be used clinically to treat a broad range of fungal infections, including skin disorders caused by Malassezia . Copyright © 2017 Ianiri et al.

  8. Disseminated Mucormycosis With Cerebral Involvement Owing to Rhizopus Microsporus in a Kidney Recipient Treated With Combined Liposomal Amphotericin B and Posaconazole Therapy.

    Science.gov (United States)

    Ville, Simon; Talarmin, Jean Philippe; Gaultier-Lintia, Alina; Bouquié, Régis; Sagan, Christine; Le Pape, Patrice; Giral, Magali; Morio, Florent

    2016-02-01

    Three months after a kidney transplant, a man experienced an internuclear ophthalmoplegia. Magnetic resonance imaging found a punctuate hyperintensity of the brainstem. Afterwards, the patient presented with peripheral facial paralysis. A complete morphologic assessment showed an increase of the brainstem lesion, together with an excavated pulmonary nodule. Combination therapy with high-dose liposomal amphotericin B and voriconazole was begun for the putative aspergillosis. Owing to its atypical clinical presentation and negative detection of Aspergillus galactomannan antigen on sera, a biopsy specimen of the lung lesion was obtained. Histopathological and mycological investigations allowed the diagnosis of mucormycosis owing to Rhizopus microsporus. Accordingly, voriconazole was replaced with posaconazole. After 5 months, regression of the cerebral lesion was noted. Disseminated mucormycosis in solid-organ recipients is uncommon and mycological diagnosis is challenging. Mortality is high and is increased by diagnostic delay. Treating mucormycosis requires surgical debridement and appropriate antifungal therapy (usually intravenous liposomal amphotericin B). This report suggests that a combination of liposomal amphotericin B and posaconazole can be a therapeutic option in patients with a poor prognosis.

  9. Changes in Incidence and Antifungal Drug Resistance in Candidemia: Results From Population-Based Laboratory Surveillance in Atlanta and Baltimore, 2008–2011

    Science.gov (United States)

    Cleveland, Angela Ahlquist; Farley, Monica M.; Harrison, Lee H.; Stein, Betsy; Hollick, Rosemary; Lockhart, Shawn R.; Magill, Shelley S.; Derado, Gordana; Park, Benjamin J.; Chiller, Tom M.

    2015-01-01

    Background Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. Methods We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008–2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992–1993; Baltimore, 1998–2000). Results We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed. PMID:22893576

  10. Susceptibility to antifungal agents and enzymatic activity of Candida haemulonii and Cutaneotrichosporon dermatis isolated from soft corals on the Brazilian reefs.

    Science.gov (United States)

    Pagani, Danielle M; Heidrich, Daiane; Paulino, Gustavo V B; de Oliveira Alves, Karine; Dalbem, Paula T; de Oliveira, Caroline F; Andrade, Zélia M M; Silva, Carolini; Correia, Monica D; Scroferneker, Maria Lúcia; Valente, Patricia; Landell, Melissa Fontes

    2016-12-01

    Candida is a common fungus with the capacity to cause infections in humans. However, most studies have concentrated on clinical isolates and little is known about the identity, ecology and drug resistance of free living species/strains. Here, we isolate eight strains of Candida haemulonii and four strains of Cutaneotrichosporon dermatis from three marine cnidarian zoanthids species (Palythoa caribaeorum, Palythoa variabilis and Zoanthus sociatus) collected from Brazilian coral reefs. Strains were identified by sequencing of the D1/D2 domain LSU rDNA and ITS region. We tested these environmental isolates for their capacity to grow in media with increasing concentration of NaCl, capacity to grow in different temperatures, enzymatic activity and antifungal susceptibility. For C. haemulonii, all strains strongly produced gelatinase, esterase and albuminase and were either able to express lipase, phospholipase and keratinase, but not express urease and DNase. The strains were able to grow at 37 °C, but not at 39 °C, and except for LMS 40, all of them could grow in a 10 % NaCl medium. All isolates were resistant to all antifungals tested, with exception for ketoconazole and tioconazole (MIC = 2 µg/mL). For C. dermatis, all strains could grow at 39 °C and could not express phospholipase, keratinase or gelatinase. However, all were capable of expressing urease, lipase and esterase. Three out of four strains could grow in a 10 % NaCl medium, but none grew in a 30 % NaCl medium. The strains showed high values of minimal inhibitory concentration. LMPV 90 was resistant to tioconazole, terbinafine, fluconazole and posaconazole, and LMS 38 was resistant to all antifungal agents tested. We discuss the characterization of C. haemulonii and C. dermatis as a possible emerging pathogen due to its animal-related enzymatic arsenal and antifungal resistance.

  11. 75 FR 16346 - Ophthalmic and Topical Dosage Form New Animal Drugs; Orbifloxacin, Mometasone Furoate Monohydrate...

    Science.gov (United States)

    2010-04-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 [Docket No... posaconazole for the treatment of otitis externa in dogs. DATES: This rule is effective April 1, 2010. FOR... posaconazole) Otic Suspension for the treatment of otitis externa in dogs associated with susceptible strains...

  12. Antifungal susceptibility of Malassezia furfur, Malassezia sympodialis, and Malassezia globosa to azole drugs and amphotericin B evaluated using a broth microdilution method.

    Science.gov (United States)

    Rojas, Florencia D; Sosa, María de los A; Fernández, Mariana S; Cattana, María E; Córdoba, Susana B; Giusiano, Gustavo E

    2014-08-01

    We studied the in vitro activity of fluconazole (FCZ), ketoconazole (KTZ), miconazole (MCZ), voriconazole (VCZ), itraconazole (ITZ) and amphotericin B (AMB) against the three major pathogenic Malassezia species, M. globosa, M. sympodialis, and M. furfur. Antifungal susceptibilities were determined using the broth microdilution method in accordance with Clinical and Laboratory Standards Institute reference document M27-A3. To support lipid-dependent yeast development, glucose, peptone, ox bile, malt extract, glycerol, and Tween supplements were added to Roswell Park Memorial Institute RPMI 1640 medium. The supplemented medium allowed good growth of all three species studied. The minimal inhibitory concentrations (MICs) were recorded after 72 h of incubation at 32ºC. The three species showed different susceptibility profiles for the drugs tested. Malassezia sympodialis was the most susceptible and M. furfur the least susceptible species. KTZ, ITZ, and VCZ were the most active drugs, showing low variability among isolates of the same species. FCZ, MCZ, and AMB showed high MICs and wide MIC ranges. Differences observed emphasize the need to accurately identify and evaluate antifungal susceptibility of Malassezia species. Further investigations and collaborative studies are essential for correlating in vitro results with clinical outcomes since the existing limited data do not allow definitive conclusions. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Posaconazole liquid suspension in solid organ transplant recipients previously treated with voriconazole.

    Science.gov (United States)

    Shoham, S; Ostrander, D; Marr, K

    2015-06-01

    Posaconazole (PCZ) has become an attractive alternative to voriconazole (VCZ) in transplant recipients with suspected or proven invasive filamentous fungal infections, causing fewer drug interactions. Here, we describe our experience with PCZ after VCZ in solid organ transplant (SOT) recipients. VCZ was replaced by PCZ liquid solution in 19 SOT recipients (15 lung, 2 kidney, 1 liver, and 1 heart/lung) with invasive pulmonary aspergillosis (12/19; 63.2%), possible invasive pulmonary fungal infection (2/19; 10.5%), prophylaxis (2/19; 10.5%), or pulmonary scedosporiosis, mucormycosis, and mixed fungal species (1 each). Rationales for switch were suspected adverse reactions to VCZ (17/19; 89.4%) and desire to broaden spectrum of coverage to include agents of mucormycosis (3/19; 15.8%). PCZ was well tolerated in all patients. In those patients with baseline liver enzyme abnormalities, a median change occurred in concentrations of alanine transaminase (-20 IU/L), aspartate aminotransferase (-17.5 IU/L), and alkaline phosphatase (-61.5 IU/L). Clinical success (resolution, stabilization, or prevention of infection) was achieved in 16/19 (84%) people. PCZ appears to have a reasonable safety and tolerability profile and may be an effective alternative in SOT patients who require an agent with anti-mold activity, but are unable to tolerate VCZ. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Antifungal pharmacodynamics: Latin America's perspective.

    Science.gov (United States)

    Gonzalez, Javier M; Rodriguez, Carlos A; Agudelo, Maria; Zuluaga, Andres F; Vesga, Omar

    The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  15. Antifungal pharmacodynamics: Latin America's perspective

    Directory of Open Access Journals (Sweden)

    Javier M. Gonzalez

    2017-01-01

    Full Text Available The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK and pharmacodynamics (PD are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins is discussed.

  16. Synergistic combinations of antifungals and antivirulence agents to fight against Candida albicans

    DEFF Research Database (Denmark)

    Cui, Jinhui; Ren, Biao; Tong, Yaojun

    2015-01-01

    -drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time......-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections....

  17. Disseminated Rhizopus microsporus infection cured by salvage allogeneic hematopoietic stem cell transplantation, antifungal combination therapy, and surgical resection.

    Science.gov (United States)

    Lebeau, O; Van Delden, C; Garbino, J; Robert, J; Lamoth, F; Passweg, J; Chalandon, Y

    2010-06-01

    Invasive Zygomycetes infection complicating prolonged neutropenia is associated with high mortality in the absence of immune recovery. We report a patient who developed disseminated zygomycosis due to Rhizopus microsporus during induction chemotherapy for acute myeloid leukemia. Rescue allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed as her only chance of cure of this infection and to treat refractory leukemia. Posaconazole combined with liposomal amphotericin B contained the zygomycosis during prolonged neutropenia due to allo-HSCT followed by intense immunosuppression for grade IV acute graft-versus-host disease. Surgical removal of all infected sites after immune recovery, with prolonged posaconazole treatment, ultimately cured the infection. New combination antifungal therapies might sufficiently control disseminated zygomycosis to allow allo-HSCT to be performed, assuring life-saving immune recovery. Surgery appears to be necessary for definite cure of these infections.

  18. Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

    Directory of Open Access Journals (Sweden)

    Paulien E. Bunskoek

    2017-06-01

    Full Text Available Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum levels of 3–9.5 mg/l were achieved without significant side-effects. Follow-up bronchoscopy and computed tomography showed complete resolution of the lesions.

  19. [Susceptibility of Candida albicans blood isolates to 3 antifungal drugs: retrospective study in Rio Grande do Sul, Brazil, 1999-2009].

    Science.gov (United States)

    Mattei, Antonella Souza; Alves, Sydney Hartz; Mario, Débora Alves; Watte, Guilherme; Severo, Cecília Bittencourt; Guazzelli, Luciana da Silva; Oliveira, Flávio de Mattos; Severo, Luiz Carlos

    2013-01-01

    Candidiasis is one of the most important among recurrent invasive yeast infections in patients, thus antifungal treatment becomes a challenge. The aim of this study was to evaluate the in vitro activity of clinical Candida albicans isolates from blood cultures to fluconazole, amphotericin B and anidulafungin, in a hospital from Rio Grande do Sul, Brazil. The susceptibility of 153 isolates to the 3 drugs mentioned was tested according to Clinical and Laboratory Standars Institute. Minimal inhibitory and fungicidal concentrations (MIC, MFC, respectively) of each drug were determined, as well as the epidemiological cutoff value (ECV). All of the isolates were susceptible to anidulafungin, MIC and MFC ≤ 1 μg/ml; however, when compared with ECV, 3% of the isolates exhibited higher values against fluconazole, 96% were susceptible, 3% susceptible dose-dependent, and 1% resistant. Also, it was observed that 21% of the isolates exhibited higher values than ECV. One isolate was resistant to amphotericin B; the other ones, susceptible, based on the MFC; furthermore, 1.5% of the isolates exhibited higher values. C. albicans isolates exhibited more susceptibility to anidulafungin, and 90% of them (MIC90) exhibited the lowest values against amphotericin B. Based on ECV and Pfaller classification, isolates could be resistant to fluconazole, demonstrating the importance of the combination of these parameters. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  20. Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

    Science.gov (United States)

    Figueroa-Ochoa, Edgar B; Villar-Alvarez, Eva M; Cambón, Adriana; Mistry, Dharmista; Llovo, José; Attwood, David; Barbosa, Silvia; Soltero, J F Armando; Taboada, Pablo

    2016-08-20

    In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Natural and synthetic peptides with antifungal activity.

    Science.gov (United States)

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections.

  2. Antifungal stewardship in a tertiary hospital.

    Science.gov (United States)

    Ramos, Antonio; Pérez-Velilla, Claudia; Asensio, Angel; Ruiz-Antorán, Belén; Folguera, Carlos; Cantero, Mireia; Orden, Beatriz; Muñez, Elena

    2015-01-01

    The inappropriate use of antifungals is an important health problem related to increasing adverse effects, unnecessary cost and promotion of resistant and emerging fungal infections. Despite its relevance, many health institutions assign few resources to improve prescribing practices. To evaluate the efficiency of an antifungal stewardship programme (ASP) centered on restricted antifungal agents. The main activity during the eight-month study was to perform a programmed review of restricted antifungals (lipid formulations of amphotericin B, echinocandins and voriconazole) prescribed in hospitalized patients. In the case of amendable antifungal treatment, a recommendation was included in the electronic medical record. A total of 280 antifungal prescriptions for 262 patients were revised during the study period. The indications were prophylactic in 85 cases (30.4%), pre-emptive in 10 cases (3.5%), empiric in 122 cases (43.6%), and directed in 63 cases (22.5%). A total of 70 prescriptions (25%) in 61 patients were considered to be amendable. In most of these cases, treatment could have been reduced considering the patient's clinical improvement and microbiological results. The most common advice was antifungals change (70%), antifungal withdrawal (21%), removal of one antifungal drug in cases of combined therapy (7%), and switching to oral route (1%). Proposed recommendations were addressed in 28 cases (40%). There was no significant difference in adherence with respect to the type of recommendation (p=0.554). There was a 42% lower use of antifungals during the period of the study compared to that observed during a similar previous period. Mortality among patients who were treated according to the recommendations of the ASP was 17% and in whom treatment was not modified it was 30% (p=0.393). ASPs centered on hospitalized patients may be an efficient strategy to ameliorate antifungal use in hospitals. Copyright © 2014 Revista Iberoamericana de Micología. Published by

  3. Local, systemic, demographic, and health-related factors influencing pathogenic yeast spectrum and antifungal drug administration frequency in oral candidiasis: a retrospective study.

    Science.gov (United States)

    Hertel, Moritz; Schmidt-Westhausen, Andrea Maria; Strietzel, Frank-Peter

    2016-09-01

    In order to identify oral candidiasis patients being at risk of carrying potentially drug-resistant Candida, the aim of the study was to detect local, systemic, demographic, and health-related factors influencing (I) yeast spectrum composition and (II) antifungal administration frequency. Additionally, the aim was to investigate (III) species shift occurrence. Data from 798 patients (496 females, 302 males; mean age 59.7) with oral candidiasis diagnosed based on positive clinical and microbial findings (species identification and CFU count) between 2006 and 2011 were retrospectively analyzed using Pearson's chi(2) test and regression analysis. Among 958 isolates, Candida albicans was the most frequently detected (76.8 %). Also, species intrinsically resistant to azoles were frequently isolated (15.8 and 17.7 % of isolates and patients). (I) Infections only caused by C. albicans were significantly associated with the use of inhalation steroids (p = 0.001) and antibiotics (p = 0.04), super-infection of lichen planus (p = 0.002), and the absence of removable dentures (p oral candidiasis remains C. albicans. Nevertheless, therapeutic problems may be caused by the frequent presence of species intrinsically resistant to azoles, especially in patients wearing dentures.

  4. Screening of antifungal azole drugs and agrochemicals with an adapted alamarBlue-based assay demonstrates antibacterial activity of croconazole against Mycobacterium ulcerans.

    Science.gov (United States)

    Scherr, Nicole; Röltgen, Katharina; Witschel, Matthias; Pluschke, Gerd

    2012-12-01

    An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans.

  5. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy.

    Science.gov (United States)

    Mast, Natalia; Lin, Joseph B; Pikuleva, Irina A

    2015-09-01

    Cytochrome P450 CYP27A1 is the only enzyme in humans converting cholesterol to 27-hydroxycholesterol, an oxysterol of multiple functions, including tissue-specific modulation of estrogen and liver X receptors. Both receptors seem to mediate adverse effects of 27-hydroxycholesterol in breast cancer when the levels of this oxysterol are elevated. The present work assessed druggability of CYP27A1 as a potential antibreast cancer target. We selected 26 anticancer and noncancer medications, most approved by the Food and Drug Administration, and evaluated them first in vitro for inhibition of purified recombinant CYP27A1 and binding to the enzyme active site. Six strong CYP27A1 inhibitors/binders were identified. These were the two antibreast cancer pharmaceuticals anastrozole and fadrozole, antiprostate cancer drug bicalutamide, sedative dexmedetomidine, and two antifungals ravuconazole and posaconazole. Anastrozole was then tested in vivo on mice, which received subcutaneous drug injections for 1 week. Mouse plasma and hepatic 27-hydroxycholesterol levels were decreased 2.6- and 1.6-fold, respectively, whereas plasma and hepatic cholesterol content remained unchanged. Thus, pharmacologic CYP27A1 inhibition is possible in the whole body and individual organs, but does not negatively affect cholesterol elimination. Our results enhance the potential of CYP27A1 as an antibreast cancer target, could be of importance for the interpretation of Femara versus Anastrozole Clinical Evaluation Trial, and bring attention to posaconazole as a potential complementary anti-breast cancer medication. More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Measuring the Impact of Gastrointestinal Variables on the Systemic Outcome of Two Suspensions of Posaconazole by a PBPK Model.

    Science.gov (United States)

    Hens, Bart; Talattof, Arjang; Paixão, Paulo; Bermejo, Marival; Tsume, Yasuhiro; Löbenberg, Raimar; Amidon, Gordon L

    2018-03-29

    For the last two decades, the application of physiologically based pharmacokinetic (PBPK) models has grown exponentially in the field of oral absorption and in a regulatory context. Although these models are widely used, their predictive power should be validated and optimized in order to rely on these models and to know exactly what is going on "under the hood". In this study, an automated sensitivity analysis (ASA) was performed for 11 gastrointestinal (GI) variables that are integrated into the PBPK software program Simcyp®. The model of interest was a previously validated workspace that was able to predict the intraluminal and systemic behavior of two different suspensions of posaconazole in the Simcyp® Simulator. The sensitivity of the following GI parameters was evaluated in this model: gastric and duodenal pH, gastric and duodenal bicarbonate concentrations (reflecting buffer capacity), duodenal bile salts concentration, gastric emptying, the interdigestive migrating motor complex (IMMC), small intestinal transit time (SITT), gastric and jejunal volumes, and permeability. The most sensitive parameters were gastric/duodenal pH and gastric emptying, for both suspensions. The outcome of the sensitivity analyses highlights the important GI variables that must be integrated into an in vivo predictive dissolution test to help and create a rational and scientific framework/design for product development of novel and generic drug products.

  7. Defensins: antifungal lessons from eukaryotes

    Directory of Open Access Journals (Sweden)

    Patrícia M. Silva

    2014-03-01

    Full Text Available Over the last years, antimicrobial peptides (AMPs have been the focus of intense research towards the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantæ and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components are presented. Additionally, recent works on antifungal defensins structure, activity and citotoxicity are also reviewed.

  8. Susceptibilidad "in vitro" de cepas de Cryptococcus a 5 drogas antifungicas "In vitro" susceptibility of Cryptococcus strains to 5 antifungal drugs

    Directory of Open Access Journals (Sweden)

    A. J. Bava

    1989-10-01

    Full Text Available Se estudió la susceptibilidad "in vitro" de 24 cepas de 3 especies del género Cryptococcus a 5 drogas antifúngicas (anfotericina B, 5 fluorocitosina, ketoconazol, itraconazol y miconazol. Las mismas se agruparon según su especie, variedad y origen de aislamiento. Para determinar la concentración inhibitoria mínima (C.I.M. de cada droga se empleó el método de dilución en agar con el medio básico nitrogenado para levaduras, adicionado de glucosa. Se obtuvo además la media geométrica de estos valores para cada grupo y se comparó cada uno de ellos. Los resultados obtenidos fueron homogéneos con la sola excepción de las cepas de Cryptococcus sp (no neoformans, en las cuales se detectaron elevados valores de C.I.M. para la 5 fluorocitosina.A comparative study of the "in vitro" susceptibility of 24 Cryptococcus strains to 5 antifungal drugs (amphotericin B, 5 fluorocytosine, miconazole, itraconazole and ketoconazole, was carried out. These strains were grouped according to species, varieties and isolation's origins. The minimum inhibitory concentration (M.I.C. was determinated by the agar dilution technique in yeast nitrogen base agar with dextrose. The mean geometrical of the M.I.C. values of each group was compared with the others. The results obtained were homogeneous with the only exception of the "non neoformans" strains, in which, higher M.I.C. to 5 fluorocytosine values were detected.

  9. Interactions between antifungal and antiretroviral agents.

    Science.gov (United States)

    Hughes, Christine A; Foisy, Michelle; Tseng, Alice

    2010-09-01

    Since the advent of combination antiretroviral therapy, the incidence of opportunistic infections has declined and the life expectancy of HIV-infected people has significantly increased. However, opportunistic infections, including fungal diseases, remain a leading cause of hospitalizations and mortality in HIV-infected people. With the availability of several new antiretroviral and antifungal agents, drug-drug interactions emerge as a potential safety concern. Relevant literature was identified using a Medline search of articles published up to March 2010 and a review of conference abstracts. Search terms included HIV, antifungal agents and drug interactions. Original papers and relevant citations were considered for this review. Readers will gain an understanding of the pharmacokinetic properties of antiretroviral and antifungal agents, and insight into significant drug-drug interactions which may require dosage adjustments or a change in therapy. Azole antifungal drugs, with the exception of fluconazole, pose the greatest risk of two-way interactions with antiretroviral drugs through CYP450 enzymes effects. Limited studies suggest the risk of interactions between antiretroviral drugs and echinocandins is much lower. The combination of tenofovir and amphotericin B should be used with caution and close monitoring of renal function is required.

  10. ANTIBACTERIAL AND ANTIFUNGAL EFFECT OF ETHANOL EXTRACTS, HEXANE AND METHANOLIC FROM THE LEAVES OF Kalanchoe pinnata (Lam. PERS (Malva corama AGAINST MULTI-DRUG RESISTANT STRAINS

    Directory of Open Access Journals (Sweden)

    Paloma de Souza Santana

    2016-03-01

    Full Text Available The infections caused by bacteria and fungi, as well as the subsequent resistance of these microorganisms continue with high incidencesthus studies of medicinal plants and their combination with conventional therapy, are becoming essential. This study examined the antibacterial, antifungal and modifier of resistance to antibiotics and antifungal extracts of ethanol, hexane and methanol from the leaves of Kalanchoe pinnata, used in folk medicine. The phytochemical was performed qualitatively by visual observation of color changes and formation of precipitates after addition of specific reagents, such as ferric chloride (Fecl310% sodium hydroxide (NaOH10%, hydrochloric acid (HCl 1%, acid  acetic acid 5%, ammonium hydroxide (NH4OH 10%, chloroform and  reagent Draggendorff 10%. The analysis for antimicrobial activity was through the microdilution test for determination of minimum inhibitory concentration (MIC and modifying the action of antibiotics (gentamicin and amikacin and antifungals (ketoconazole and fluconazole in association with the extracts. The phytochemicals assays indicated the presence of secondary metabolites such as flavonoids, alkaloids and flabobênicos tannins. In assessing the MIC results were obtained <1024μg/ mL for Candida albicans and Candida krusei. There was synergism between extracts of Kalanchoe pinnata leaves with aminoglycosides and antifungal, reducing the concentration of CIM of multidrug-resistant strains. Our results demonstrate that the extracts of Kalanchoe pinnata have bioactive constituents with antimicrobial activity in vitro. Keywords: Kalcinchoe pinnata, Microorganisms, Synergistic effect, Antifungal, Antibacterial.

  11. Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cutoff values.

    Science.gov (United States)

    Pfaller, M A; Rhomberg, P R; Messer, S A; Jones, R N; Castanheira, M

    2015-08-01

    The in vitro activities of isavuconazole, micafungin, and 8 comparator antifungal agents were determined for 1613 clinical isolates of fungi (1320 isolates of Candida spp., 155 of Aspergillus spp., 103 of non-Candida yeasts, and 35 non-Aspergillus molds) collected during a global survey conducted in 2013. The vast majority of the isolates of the 21 different species of Candida, with the exception of Candida glabrata (MIC90, 2 μg/mL), Candida krusei (MIC90, 1 μg/mL), and Candida guilliermondii (MIC90, 8 μg/mL), were inhibited by ≤0.25 μg/mL of isavuconazole. C. glabrata and C. krusei were largely inhibited by ≤1 μg/mL of isavuconazole. Resistance to fluconazole was seen in 0.5% of Candida albicans isolates, 11.1% of C. glabrata isolates, 2.5% of Candida parapsilosis isolates, 4.5% of Candida tropicalis isolates, and 20.0% of C. guilliermondii isolates. Resistance to the echinocandins was restricted to C. glabrata (1.3-2.1%) and C. tropicalis (0.9-1.8%). All agents except for the echinocandins were active against 69 Cryptococcus neoformans isolates, and the triazoles, including isavuconazole, were active against the other yeasts. Both the mold active triazoles as well as the echinocandins were active against 155 Aspergillus spp. isolates belonging to 10 species/species complex. In general, there was low resistance levels to the available systemically active antifungal agents in a large, contemporary (2013), global collection of molecularly characterized yeasts and molds. Resistance to azoles and echinocandins was most prominent among isolates of C. glabrata, C. tropicalis, and C. guilliermondii. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The role of the multidisciplinary team in antifungal stewardship

    NARCIS (Netherlands)

    Agrawal, S.; Barnes, R.; Bruggemann, R.J.; Rautemaa-Richardson, R.; Warris, A.

    2016-01-01

    There are a variety of challenges faced in the management of invasive fungal diseases (IFD), including high case-fatality rates, high cost of antifungal drugs and development of antifungal resistance. The diagnostic challenges and poor outcomes associated with IFD have resulted in excessive

  13. Spectrophotometric reading of EUCAST antifungal susceptibility testing of Aspergillus fumigatus

    NARCIS (Netherlands)

    Meletiadis, J.; Mortensen, K.L.; Verweij, P.E.; Mouton, J.W.; Arendrup, M.C.

    2017-01-01

    OBJECTIVES: Given the increasing number of antifungal drugs and the emergence of resistant Aspergillus isolates, objective, automated and high-throughput antifungal susceptibility testing is important. The EUCAST E.Def 9.3 reference method for MIC determination of Aspergillus species relies on

  14. Antifungal activity of crude extracts of Gladiolus dalenii van Geel ...

    African Journals Online (AJOL)

    Bulb extracts of Gladiolus dalenii reportedly used in the treatment of fungal infections in HIV/AIDS patients in the Lake Victoria region were tested for antifungal activity using the disc diffusion assay technique. Commercially used antifungal drugs, Ketaconazole and Griseofulvin (Cosmos Pharmaceuticals) were used as ...

  15. Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation.

    Science.gov (United States)

    Pettit, Natasha N; Miceli, Marisa H; Rivera, Christina G; Narayanan, Prasanna P; Perissinotti, Anthony J; Hsu, Meier; Delacruz, Jennifer; Gedrimaite, Zivile; Han, Zhe; Steinbeck, Jennifer; Pisano, Jennifer; Seo, Susan K; Paskovaty, Alla

    2017-08-01

    The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxic medications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST ( P  <   0.001), ALT ( P  <   0.001), alkaline phosphatase (ALK) ( P  <   0.001), total bilirubin (TBILI) ( P  <   0.001) and QTc ( P  =   0.05) from baseline. Posaconazole levels were not associated with increases in AST [β (SE) = -0.33 (2.2), P  =   0.88], log ALT [β (SE) = -0.02 (0.03), P  =   0.63], ALK [β (SE) = 2.2 (2.9), P  =   0.46] and TBILI [β (SE) = -0.01 (0.04), P  =   0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL ( P  =   0.02) and ALK of 7.1 U/L ( P  =   0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered. © The Author 2017. Published by Oxford University Press on behalf of the British Society

  16. Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.

    Science.gov (United States)

    Pfaller, Michael A; Castanheira, Mariana

    2016-01-01

    Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility testing of 10 systemically active antifungal agents when tested against Candida spp.

    Science.gov (United States)

    Pfaller, Michael A; Castanheira, Mariana; Messer, Shawn A; Rhomberg, Paul R; Jones, Ronald N

    2014-06-01

    The antifungal broth microdilution (BMD) method of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was compared with Clinical and Laboratory Standards Institute (CLSI) BMD method M27-A3 for amphotericin B, flucytosine, anidulafungin, caspofungin, micafungin, fluconazole, isavuconazole, itraconazole, posaconazole, and voriconazole susceptibility testing of 357 isolates of Candida. The isolates were selected from global surveillance collections to represent both wild-type (WT) and non-WT MIC results for the azoles (12% of fluconazole and voriconazole results were non-WT) and the echinocandins (6% of anidulafungin and micafungin results were non-WT). The study collection included 114 isolates of Candida albicans, 73 of C. glabrata, 76 of C. parapsilosis, 60 of C. tropicalis, and 34 of C. krusei. The overall essential agreement (EA) between EUCAST and CLSI results ranged from 78.9% (posaconazole) to 99.6% (flucytosine). The categorical agreement (CA) between methods and species of Candida was assessed using previously determined CLSI epidemiological cutoff values. The overall CA between methods was 95.0% with 2.5% very major (VM) and major (M) discrepancies. The CA was >93% for all antifungal agents with the exception of caspofungin (84.6%), where 10% of the results were categorized as non-WT by the EUCAST method and WT by the CLSI method. Problem areas with low EA or CA include testing of amphotericin B, anidulafungin, and isavuconazole against C. glabrata, itraconazole, and posaconazole against most species, and caspofungin against C. parapsilosis, C. tropicalis, and C. krusei. We confirm high level EA and CA (>90%) between the 2 methods for testing fluconazole, voriconazole, and micafungin against all 5 species. The results indicate that the EUCAST and CLSI methods produce comparable results for testing the systemically active antifungal agents against the 5 most common species of Candida; however, there are several areas where additional

  18. Novel Antifungal Compounds Discovered in Medicines for Malaria Venture's Malaria Box.

    Science.gov (United States)

    Jung, Eric H; Meyers, David J; Bosch, Jürgen; Casadevall, Arturo

    2018-01-01

    Similarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole against Cryptococcus neoformans . There was also significant antifungal activity in other fungal species with known antifungal resistance, such as Lomentospora prolificans and Cryptococcus gattii . Antifungal activity was also observed against a common fungus, Candida albicans . These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics. IMPORTANCE Much like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity in Plasmodium spp. for activity against two common fungal pathogens, Cryptococcus neoformans and Candida albicans , along with two less common pathogenic species, Lomentospora prolificans and Cryptococcus gattii . We

  19. A Study on the Frequency of Fungal Rhinosinusitis and to Determine the Sensitivity of the Isolates to Antifungal Drugs in Shiraz, Iran 2012-2013

    Directory of Open Access Journals (Sweden)

    Parisa Badiei

    2015-06-01

    Full Text Available Abstract Background: Fungal spores are present in large amounts in the nature which may cause diseases in the susceptible individuals. Fungal rhinosinusitis has been increased during recent decades. This study aims to investigate fungal rhinosinusitis in the patients with chronic needing endoscopic sinus surgery aims and to determine the sensitivity of the isolates to rhin sinusitis antifungal agents. Materials and Methods: In cross sectional study, specimens were obtained in sterile plates containing normal saline. from the suspected cases of chronic rhinosinusitis who had undergone endoscopic sinus surgery. Microscopic experiments and Cultures were done in Sabouraud Dextrose Agar medium. Minimum inhibitory concentration (MIC of the growth of fungi for seven antifungal agents against the isolates was determined using E-Test. Results: In total, specimens from 102 immunocompetent patients were examined. Nine positive specimens were presented, consisting of 3 for Aspergillus fumigatus, 3 for Penicillium, 2 for Aspergillus flavus and 1 for Alternaria. The mean age of the patients was 38 years, with 59 males and 43 females. The isolates were most sensitive to the voriconazole and amphotericin B. Conclusion: Since the prevalence of fungal rhinosinusitis is low, unfortunately, the clinicians are not attentive enough to the condition, and they initiate antifungal therapy if the patients are not responsive to antibiotics. Early diagnosis and suitable treatment can help more efficient management of patients.

  20. Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

    Science.gov (United States)

    Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M; Kuusniemi, Kristiina; Backman, Janne T; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J; Olkkola, Klaus T; Saari, Teijo I

    2016-11-01

    This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC 0-∞ ) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.

  1. Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

    NARCIS (Netherlands)

    P.E. Bunskoek (Paulien); S. Seyedmousavi (Seyedmojtaba); S. Gans (Steven); van Vierzen, P.B.J. (Peter B.J.); W.J. Melchers (Willem); C.E. van Elk; J.W. Mouton (Johan); P.E. Verweij (Paul)

    2017-01-01

    textabstractInvasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded,

  2. Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution.

    Science.gov (United States)

    Hines, C D G; Song, X; Kuruvilla, S; Farris, G; Markgraf, C G

    2015-01-01

    Noxafil® (posaconazole; POS) is a potent, selective triazole antifungal approved for use in adults as an oral suspension, oral tablet and intravenous (IV) Solution. In support of pediatric administration of POS IV Solution to childrentwo years of age, two studies were undertaken using magnetic resonance imaging (MRI) to monitor brain ventricle size longitudinally during three months administration of POS IV in adult and juvenile dogs. Necropsy was performed on all animals at the end of the studies. From the baseline MRI images, great variability in ventricle size was noted in both the adult and juvenile dogs; these images were used to distribute differently sized ventricles between treatment and vehicle groups as to not skew group means during the course of the study. POS IV Solution had no effect on ventricle volume at any timepoint during dosing in either the adult or the juvenile dogs. Further, no gross or histomorphologic differences between groups were observed in either study. Compared to juvenile dogs, MRI analysis showed that adult dogs had larger ventricles, lower variability in all ventricle volumes, and a greater rate of increase in total ventricle volume. Information on growth and development of brains is one of the few areas in which more detailed information is available about humans than about the standard laboratory animals used to model disease and predict toxicities. The use of MRI helped elucidate large natural variabilities in the dog brain, which could have altered the interpretation of this de-risking study, and provided a valuable noninvasive means to monitor the brain ventricles longitudinally. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Antifungal compounds from cyanobacteria.

    Science.gov (United States)

    Shishido, Tânia K; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P; Permi, Perttu; Andreote, Ana P D; Fiore, Marli F; Sivonen, Kaarina

    2015-04-13

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.

  4. Rhodanineacetic Acid Derivatives as Potential Drugs: Preparation, Hydrophobic Properties and Antifungal Activity of (5-Arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-ylacetic Acids

    Directory of Open Access Journals (Sweden)

    Josef Jampilek

    2009-10-01

    Full Text Available Some [(5Z-(5-arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acids were prepared as potential antifungal compounds. The general synthetic approach to all synthesized compounds is presented. Lipophilicity of all the discussed rhodanine-3-acetic acid derivatives was analyzed using a reversed phase high performance liquid chromatography (RP-HPLC method. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary RP column. The RP-HPLC retention parameter log k (the logarithm of the capacity factor k is compared with log P values calculated in silico. All compounds were evaluated for antifungal effects against selected fungal species. Most compounds exhibited no interesting activity, and only {(5Z-[4-oxo-5-(pyridin-2- ylmethylidene-2-thioxo-1,3-thiazolidin-3-yl]}acetic acid strongly inhibited the growth of Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I and Trichosporon asahii 1188.

  5. Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial.

    Science.gov (United States)

    Morillo, Carlos A; Waskin, Hetty; Sosa-Estani, Sergio; Del Carmen Bangher, Maria; Cuneo, Carlos; Milesi, Rodolfo; Mallagray, Marcelo; Apt, Werner; Beloscar, Juan; Gascon, Joaquim; Molina, Israel; Echeverria, Luis E; Colombo, Hugo; Perez-Molina, Jose Antonio; Wyss, Fernando; Meeks, Brandi; Bonilla, Laura R; Gao, Peggy; Wei, Bo; McCarthy, Michael; Yusuf, Salim

    2017-02-28

    Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days. Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yi; Tenor, Jennifer L.; Toffaletti, Dena L.; Maskarinec, Stacey A.; Liu, Jiuyu; Lee, Richard E.; Perfect, John R.; Brennan, Richard G.; Hendrickson, Wayne A.

    2017-07-25

    ABSTRACT

    The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 fromCandida albicansandAspergillus fumigatusare essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellular analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes.

    IMPORTANCEInvasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in

  7. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles

    Directory of Open Access Journals (Sweden)

    Ravikumar Bapurao Shinde

    Full Text Available Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p < 0.05 in presence of 250 µg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.

  8. A case of Candida famata sepsis in a very low birth weight infant successfully treated with fluconazole following antifungal susceptibility testing

    Directory of Open Access Journals (Sweden)

    Shilpee Raturi

    2015-01-01

    This case report highlights the growing number of cases arising due to nonalbicans Candida infections in the neonatal intensive care units and the usefulness of antifungal susceptibility testing in deciding optimal antifungal therapy and preventing the emergence of drug resistance.

  9. Antifungal susceptibilities of Candida glabrata species complex, Candida krusei, Candida parapsilosis species complex and Candida tropicalis causing invasive candidiasis in China: 3 year national surveillance.

    Science.gov (United States)

    Xiao, Meng; Fan, Xin; Chen, Sharon C-A; Wang, He; Sun, Zi-Yong; Liao, Kang; Chen, Shu-Lan; Yan, Yan; Kang, Mei; Hu, Zhi-Dong; Chu, Yun-Zhuo; Hu, Tie-Shi; Ni, Yu-Xing; Zou, Gui-Ling; Kong, Fanrong; Xu, Ying-Chun

    2015-03-01

    To define the antifungal susceptibility patterns of the most common non-albicans Candida spp. in China. We evaluated the susceptibilities to nine antifungal drugs of Candida parapsilosis species complex, Candida tropicalis, Candida glabrata species complex and Candida krusei isolates from patients with invasive candidiasis at 11 hospitals over 3 years. Isolates were identified by MALDI-TOF MS supplemented by DNA sequencing. MICs were determined by Sensititre YeastOne(TM) using current clinical breakpoints/epidemiological cut-off values to assign susceptibility (or WT), and by CLSI M44-A2 disc diffusion for fluconazole and voriconazole. Of 1072 isolates, 392 (36.6%) were C. parapsilosis species complex. C. tropicalis, C. glabrata species complex and C. krusei comprised 35.4%, 24.3% and 3.7% of the isolates, respectively. Over 99.3% of the isolates were of WT phenotype to amphotericin B and 5-flucytosine. Susceptibility/WT rates to azoles among C. parapsilosis species complex were ≥97.5%. However, 11.6% and 9.5% of C. tropicalis isolates were non-susceptible to fluconazole and voriconazole, respectively (7.1% were resistant to both). Approximately 14.3% of C. glabrata sensu stricto isolates (n = 258) were fluconazole resistant, and 11.6% of C. glabrata sensu stricto isolates were cross-resistant to fluconazole and voriconazole. All C. krusei isolates were susceptible/WT to voriconazole, posaconazole and itraconazole. Overall, 97.7%-100% of isolates were susceptible to caspofungin, micafungin and anidulafungin, but 2.3% of C. glabrata were non-susceptible to anidulafungin. There was no azole/echinocandin co-resistance. Disc diffusion and Sensititre YeastOne(TM) methods showed >95% categorical agreement for fluconazole and voriconazole. In summary, reduced azole susceptibility was seen among C. tropicalis. Resistance to echinocandins was uncommon. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  10. Econazole imprinted textiles with antifungal activity.

    Science.gov (United States)

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis.

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    Yoshiki Matsuda

    Full Text Available Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%. Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20% in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients.

  12. Suscetibilidade a antifúngicos de cepas de Candida albicans isoladas de pacientes com estomatite protética Susceptibility to antifungal drugs of Candida albicans strains isolated from patients with denture stomatitis

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    Jéssica Moreira BATISTA

    1999-12-01

    Full Text Available Pacientes portadores de próteses totais, apresentam, com freqüência a chamada estomatite protética, com a qual associa-se Candida albicans determinando a chamada candidíase eritematosa. Assim, procuramos avaliar a suscetibilidade dessa levedura a agentes antifúngicos. A suscetibilidade de dezenove cepas de Candida albicans isoladas de pacientes apresentando estomatite protética foi estudada frente a: um derivado poliênico representado, pela anfotericina B (AnB, e dois derivados azóicos, cetoconazol e miconazol. A atividade antifúngica foi estudada a partir da determinação da concentração inibitória mínima (CIM e da concentração fungicida mínima (CFM, pela técnica de diluição em ágar. Os resultados obtidos, mostraram baixos valores de CIMs e CFMs (mg/ml para a AnB frente a todas as leveduras. Para o miconazol e o cetoconazol, foram observadas CIMs invariavelmente £ 4,00 mg/ml; para as CFMs, foram obtidos valores ³ 16,00 mg/ml frente a maioria das cepas. Conclui-se que a AnB apresentou maior ação fungicida in vitro enquanto os azóis demonstraram ação fungistática mas não fungicida. Acreditamos que a pesquisa de novas drogas, principalmente de uso tópico ainda é necessária, a fim de se tratar, com sucesso, a candidíase eritematosa, comumente observada nas chamadas estomatites protéticas.Users of total prosthesis present in general a high frequency of the so called denture stomatitis, associated to erythematous candidiasis. So, we evaluated the susceptibility of oral yeast to three antifungal agents. Strains of Candida albicans isolated from patients with denture stomatitis were evaluated in relation to the susceptibility of the antifungal drugs as amphotericin B (polyenic derivatives, and azole agents as ketoconazole and miconazole. The antifungal activity was evaluated, and the minimal inhibitory concentration (MIC and minimal fungicide concentration (MFC were determined utilizing the agar dilution method. The

  13. Design of amphotericin B oral formulation for antifungal therapy.

    Science.gov (United States)

    Liu, Min; Chen, Meiwan; Yang, Zhiwen

    2017-11-01

    Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

  14. Antifungal agents in non-neonatologic pediatrics

    Directory of Open Access Journals (Sweden)

    Elio Castagnola

    2013-07-01

    Full Text Available The spectrum of action of antifungal agents helps driving the choice of the treatment, basing on the activity against the fungus of interest. Pharmacokinetics should also be taken into account, considering the time-dependent and the concentration-dependent drugs. Triazoles belong to the first group, while amphotericin B and echinocandins belong to the second one. The effectiveness of time-dependent drugs hangs on the time spent above the Minimal Inhibitory Concentration (MIC, whereas that of concentration-dependent drugs is related to the peak of concentration achieved. Thetissue penetration is another important factor that should be taken into account while prescribing an antifungal agent. Interactions with other drugs, above all with those used to treat underlying pathologies, should also be considered. Fungicidal drugs are generally preferred to fungistatic agents, therefore echinocandins and amphotericin B are more prescribed than azoles. Combination therapies are not recommended.http://dx.doi.org/10.7175/rhc.v4i1S.860

  15. Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

    OpenAIRE

    Almeida-Paes, Rodrigo; Brito-Santos, Fábio; Figueiredo-Carvalho, Maria Helena Galdino; Machado, Ana Caroline Sá; Oliveira, Manoel Marques Evangelista; Pereira, Sandro Antonio; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely Maria

    2017-01-01

    BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study ...

  16. Spectrophotometric reading of EUCAST antifungal susceptibility testing of Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Meletiadis, J.; Leth Mortensen, K.; Verweij, P. E.

    2017-01-01

    Objectives Given the increasing number of antifungal drugs and the emergence of resistant Aspergillus isolates, objective, automated and high-throughput antifungal susceptibility testing is important. The EUCAST E.Def 9.3 reference method for MIC determination of Aspergillus species relies on vis...

  17. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

    OpenAIRE

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, F?bio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancop?-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensi...

  18. Antifungal therapy in European hospitals

    DEFF Research Database (Denmark)

    Zarb, P; Amadeo, B; Muller, A

    2012-01-01

    The study aimed to identify targets for quality improvement in antifungal use in European hospitals and determine the variability of such prescribing. Hospitals that participated in the European Surveillance of Antimicrobial Consumption Point Prevalence Surveys (ESAC-PPS) were included. The WHO...... of 40,878 (3.7%) antimicrobials. Antifungals were mainly (54.2%) administered orally. Hospital-acquired infections represented 44.5% of indications for antifungals followed by medical prophylaxis at 31.2%. The site of infection was not defined in 36.0% of cases but the most commonly targeted sites were...... respiratory (19.2%) and gastrointestinal (18.8%). The most used antifungal was fluconazole (60.5%) followed by caspofungin (10.5%). Antifungal-antibacterial combinations were frequently used (77.5%). The predominance of fluconazole use in participating hospitals could result in an increase in prevalence...

  19. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Directory of Open Access Journals (Sweden)

    Deepa Gupta

    2015-01-01

    Full Text Available Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

  20. Antifungal activity of streptomycetes isolated bentonite clay

    Directory of Open Access Journals (Sweden)

    V. P. Shirobokov

    2016-12-01

    synthesized into the broth and present in bacterial biomass. Conclusions. Secondary metabolites from antifungal properties are accumulated both in Streptomyces SVP-71 biomass and in the culture fluid. The obtained extracts can be used to create antifungal drugs.

  1. Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

    Science.gov (United States)

    2014-01-01

    Background Sporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. Sporothrix infections notably occur in outbreaks, with large epidemics currently taking place in southeastern Brazil and northeastern China. Pathogenic species include Sporothrix brasiliensis, Sporothrix schenckii s. str., Sporothrix globosa, and Sporothrix luriei, which exhibit differing geographical distribution, virulence, and resistance to antifungals. The phylogenetically remote species Sporothrix mexicana also shows a mild pathogenic potential. Methods We assessed a genetically diverse panel of 68 strains. Susceptibility profiles of medically important Sporothrix species were evaluated by measuring the MICs and MFCs for amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS). Haplotype networks were constructed to reveal interspecific divergences within clinical Sporothrix species to evaluate genetically deviant isolates. Results ITC and PCZ were moderately effective against S. brasiliensis (MIC90 = 2 and 2 μg/mL, respectively) and S. schenckii (MIC90 = 4 and 2 μg/mL, respectively). PCZ also showed low MICs against the rare species S. mexicana. 5FC, CAS, and FLC showed no antifungal activity against any Sporothrix species. The minimum fungicidal concentration ranged from 2 to >16 μg/mL for AMB against S. brasiliensis and S. schenckii, while the MFC90 was >16 μg/mL for ITC, VRC, and PCZ. Conclusion Sporothrix species in general showed high degrees of resistance against antifungals. Evaluating a genetically diverse panel of strains revealed evidence of multidrug resistant phenotypes, underlining the need for molecular identification of etiologic agents to predict therapeutic outcome. PMID:24755107

  2. The successful use of amphotericin B followed by oral posaconazole in a rare case of invasive fungal sinusitis caused by co-infection with mucormycosis and aspergillus

    Directory of Open Access Journals (Sweden)

    Sharana Mahomed

    2015-01-01

    Full Text Available We report on an unusual case of oro-rhinocerebral disease caused by mucormycosis and aspergillus co-infection in a 54-year-old insulin dependent diabetic patient. Although she was successfully treated with parenteral amphotericin B followed by oral posaconazole, she was left with irreversible blindness of the right eye and multiple cranial nerve palsies.

  3. Genetic determinants of antifungal resistance in Candida species ...

    African Journals Online (AJOL)

    In the previous decades, it has been an increase in cases of resistance to antifungal agents used in the prophylaxis and treatment of infections caused by Candida species. The emergence of resistance to drug classes, it is usually explained by genome alterations ranging from point mutations to gain or loss of whole ...

  4. Evaluation of antibacterial, antifungal and modulatory activity of ...

    African Journals Online (AJOL)

    Methods: The tests for the minimum inhibitory concentration and modulation of microbial resistance, with the use of ethanolic and methanolic extracts of Padina Sanctae-cruces combined with drugs of the class of aminoglycosides and antifungal were used to evaluate the activity against the cited microorganisms. Results: ...

  5. In vitro assay of potential antifungal and antibacterial activities of ...

    African Journals Online (AJOL)

    ... the dermatophytes strains Trichophyton rubrum, Trichophyton interdigitale, Trichophyton soudanense, Microsporum langeronii, and Epidermophyton floccosum were used. The E2F2 extract showed strong inhibitory activity on four of the five fungal species used against ketoconazole, a standard antifungal drug. However ...

  6. Antifungal susceptibility profiles and risk factors of vaginal ...

    African Journals Online (AJOL)

    Antifungal susceptibility results showed a high resistance to fluconazole (82.0%), nystatin (80.0%) and ketoconazole (72.0%), while clotrimazole (50.0%) was the most activeantifungal drug. There was a high prevalence of VC in this study population with previous vaginal infectionbeing important risk factor for reoccurrence.

  7. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    Directory of Open Access Journals (Sweden)

    Marie Desnos-Ollivier

    Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

  8. Antifungal susceptibility testing for yeasts: how, when and why, according to the new EUCAST guidelines

    Directory of Open Access Journals (Sweden)

    Esther Manso

    2011-03-01

    Full Text Available Antifungal susceptibility testing of yeasts and the development of interpretive breakpoints are nowadays very important topics both for the increasing incidence of invasive mycoses and number of available antifungal drugs and for the appearance of acquired resistance. The Subcommittee on Antifungal Susceptibility Testing (AFST of the European Committee on Antibiotic Susceptibility Testing (EUCAST has recently released both the operative standards to evaluate the fermenting yeasts susceptibility against antimycotic drugs and the breakpoints for infections due to some Candida species and for some of the available antifungals. Antifungal susceptibility testing is mandatory on a routine base for: 1. therapeutic failure, 2. breakthrough fungemias, 3. on yeasts isolated from patients who recently received prophylactic antifungal treatments, and 4. when the deep-seated infection is due to less common yeasts, with an unknown susceptibility pattern. The Medical Mycology Committee (CoSM of the Italian Society of Clinical Microbiologists (AMCLI adopted the interpretive breakpoints of both CLSI and EUCAST. The operating procedure for antifungal susceptibility testing according to EUCAST is supported by the recommendation to use, when clinically necessary, validated commercial methods (Vitek2, Sensititre, E-test. Finally, the CoSM reports the recommendations for a correct management of antifungal susceptibility testing.

  9. Looking for new antifungal drugs from flavonoids: impact of the genetic diversity of Candida albicans on the in-vitro response.

    Science.gov (United States)

    Felice, Maria Rosa; Giuffre, Letterio; El Aamri, Lamya; Hafidi, Majida; Criseo, Giuseppe; Romeo, Orazio; Scordino, Fabio

    2017-12-25

    In an era in which antimicrobial resistance is increasing at an alarming pace, it's very important to find new antimicrobial agents effective against pathogenic microrganisms resistant to traditional treatments. Among the notable breakthroughs in the past years of research in natural-drug discovery there is the identification and testing of flavonoids, a group of plant-derived substances capable of promoting many beneficial effects on humans. These compounds show different biological activities such as inhibition of neuroinflammation and tumor growth as well as antidepressant, antiarthritic, anti-hypercholesterolemic, antidiabetic, antiulcer and antiasthmatic activities. However, one of the most important effects of these phytochemicals is, undoubtedly, their antimicrobial activity against many microbial pathogens. In recent years, hundreds of scientific papers reported the inhibitory effects of flavonoids against pathogenic fungi but none of these has ever considered the inexorable genetic changes occurring within the populations of these microrganisms. Today, we have enough information to estimate genetic diversity within microbial species and recent data revealed that most of fungal pathogens shows a complex population structure in which no a single isolate can be designate as representative of the entire taxon. This is especially true for the highly divergent fungal pathogen Candida albicans, in which the assumption that one or few "standard strains" can represent the whole species is overly unrealistic and should be laid to rest. The goal of this article is to shed light on the extent of genetic variation in C. albicans and how this phenomenon can largely influence the activity of flavonoids against this species. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Antifungal activity of Myrtus communis against Malassezia sp. isolated from the skin of patients with pityriasis versicolor.

    Science.gov (United States)

    Barac, Aleksandra; Donadu, Matthew; Usai, Donatella; Spiric, Vesna Tomic; Mazzarello, Vittorio; Zanetti, Stefania; Aleksic, Ema; Stevanovic, Goran; Nikolic, Natasa; Rubino, Salvatore

    2017-11-20

    The increasing incidence of fungal infections and antifungal resistance has prompted the search for novel antifungal drugs and alternative agents. We explored the antifungal activity of Myrtus communis essential oil (EO) against Malassezia sp. isolated from the skin of patients with pityriasis versicolor. These broad-spectrum antimicrobial activities of M. communis EO and its potent inhibiting activity on Malassezia growth deserve further research with aim to considerate this EO as candidate for topical use in treatment of skin diseases.

  11. Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

    Directory of Open Access Journals (Sweden)

    Fábio Silvestre Ataides

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis , and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin.METHODS:Differentiation of C. parapsilosis complex species was performed by amplification of the secondary alcohol dehydrogenase (SADH gene and digestion by the restriction enzyme Ban I. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing.RESULTS:Among the 87 isolates, 78 (89.7% were identified as C. parapsilosis sensu stricto , five (5.7% were identified as C. orthopsilosis , and four (4.6% were identified as C. metapsilosis . Analysis of antifungal susceptibility showed that C. parapsilosis sensu strictoisolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu strictoisolates and one C. metapsilosis isolate were susceptible to fluconazole in a dose-dependent manner.CONCLUSIONS:We reported the first molecular identification of C. parapsilosiscomplex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profiles, the primary susceptibility of this species was to caspofungin.

  12. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    Science.gov (United States)

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

    Science.gov (United States)

    Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2015-01-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  14. Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids

    Science.gov (United States)

    Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.

    2011-05-01

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.

  15. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges.

    Science.gov (United States)

    Soliman, Ghareb M

    2017-05-15

    Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient dermatology clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulation options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review sheds light on different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

    Science.gov (United States)

    Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

    2008-01-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

  17. Potent in vitro antifungal activities of naturally occurring acetylenic acids.

    Science.gov (United States)

    Li, Xing-Cong; Jacob, Melissa R; Khan, Shabana I; Ashfaq, M Khalid; Babu, K Suresh; Agarwal, Ameeta K; Elsohly, Hala N; Manly, Susan P; Clark, Alice M

    2008-07-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C(16) to C(20): 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 muM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 mumol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies.

  18. Trypanocide, cytotoxic, and antifungal activities of Momordica charantia.

    Science.gov (United States)

    Santos, Karla K A; Matias, Edinardo F F; Sobral-Souza, Celestina E; Tintino, Saulo R; Morais-Braga, Maria F B; Guedes, Glaucia M M; Santos, Francisco A V; Sousa, Ana Carla A; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique D M

    2012-02-01

    Chagas disease, caused by Trypanosoma cruzi, is a public health problem. Currently, chemotherapy is the only available treatment for this disease, and the drugs used, nifurtimox and benzonidazol, present high toxicity levels. An alternative for replacing these drugs are natural extracts from Momordica charantia L. (Cucurbitaceae) used in traditional medicine because of their antimicrobial and biological activities. In this study, we evaluated the extract of M. charantia for its antiepimastigote, antifungal, and cytotoxic activities. An ethanol extract of leaves from M. charantia was prepared. To research in vitro antiepimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1 × 10(5) cells/mL in 200 µl tryptose-liver infusion. For the cytotoxicity assay, J774 macrophages were used. The antifungal activity was evaluated by microdilution using strains of Candida albicans, Candida tropicalis, and Candida krusei. The effective concentration capable of killing 50% of parasites (IC(50)) was 46.06 µg/mL. The minimum inhibitory concentration (MIC) was ≤ 1024 µg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with an extract of M. charantia. Our results indicate that M. charantia could be a source of plant-derived natural products with antiepimastigote and antifungal-modifying activity with moderate toxicity.

  19. Candida Species Biofilms’ Antifungal Resistance

    Science.gov (United States)

    Silva, Sónia; Rodrigues, Célia F.; Araújo, Daniela; Rodrigues, Maria Elisa; Henriques, Mariana

    2017-01-01

    Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. PMID:29371527

  20. Penetratin and derivatives acting as antifungal agents

    NARCIS (Netherlands)

    Masman, Marcelo F.; Rodriguez, Ana M.; Raimondi, Marcela; Zacchino, Susana A.; Luiten, Paul G. M.; Somlai, Csaba; Kortvelyesi, Tamas; Penke, Botond; Enriz, Ricardo D.

    The synthesis, in vitro evaluation, and conformational study of RQIKTWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC

  1. SHORT COMMUNICATION EVALUATION OF ANTIFUNGAL AND ...

    African Journals Online (AJOL)

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    Pakistan) and chloramphenicol from Sigma St. Louis. (USA) was used as standard. Antifungal activity of monoesters. The antifungal activities of the monoesters (1-29) were determined by employing hanging drop method considering ketoconazole ...

  2. DYSREGULATION OF ION HOMEOSTASIS BY ANTIFUNGAL AGENTS

    Directory of Open Access Journals (Sweden)

    Yongqiang eZhang

    2012-04-01

    Full Text Available Ion signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose dependent Ca2+ burst and long lasting pH changes in the model yeast S. cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

  3. Microbial biotransformation to obtain new antifungals

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Bianchini

    2015-12-01

    Full Text Available Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1 microbial biotransformation of herbal medicines and food; (2 possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3 methodological improvements in processes involving whole cells and immobilized enzymes; (4 potential of endophytic fungi to produce antimicrobials by bioconversions; and (5 in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called green chemistry, which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact.

  4. Microbial Biotransformation to Obtain New Antifungals

    Science.gov (United States)

    Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  5. Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies.

    Science.gov (United States)

    Gamaletsou, Maria N; Walsh, Thomas J; Sipsas, Nikolaos V

    2018-03-01

    Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better

  6. Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies

    Directory of Open Access Journals (Sweden)

    Maria N. Gamaletsou

    2018-02-01

    Full Text Available Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods

  7. Antifungal Treatment for Pityriasis Versicolor.

    Science.gov (United States)

    Gupta, Aditya K; Foley, Kelly A

    2015-03-12

    Pityriasis versicolor (PV), also known as tinea versicolor, is caused by Malassezia species. This condition is one of the most common superficial fungal infections worldwide, particularly in tropical climates. PV is difficult to cure and the chances for relapse or recurrent infections are high due to the presence of Malassezia in the normal skin flora. This review focuses on the clinical evidence supporting the efficacy of antifungal treatment for PV. A systematic review of literature from the PubMed database was conducted up to 30 September 2014. The search criteria were "(pityriasis versicolor OR tinea versicolor) AND treatment", with full text available and English language required. Topical antifungal medications are the first-line treatment for PV, including zinc pyrithione, ketoconazole, and terbinafine. In cases of severe or recalcitrant PV, the oral antifungal medications itraconazole and fluconazole may be more appropriate, with pramiconazole a possible future option. Oral terbinafine is not effective in treating PV and oral ketoconazole should no longer be prescribed. Maintenance, or prophylactic, therapy may be useful in preventing recurrent infection; however, at this time, there is limited research evaluating the efficacy of prophylactic antifungal treatment.

  8. Antifungal activity of multifunctional Fe{sub 3}O{sub 4}-Ag nanocolloids

    Energy Technology Data Exchange (ETDEWEB)

    Chudasama, Bhupendra, E-mail: bnchudasama@thapar.ed [School of Physics and Materials Science, Thapar University, Patiala 147004 (India); Vala, Anjana K.; Andhariya, Nidhi [Department of Physics, Bhavnagar University, Bhavnagar 364022 (India); Upadhyay, R.V. [P.D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421 (India); Mehta, R.V. [Department of Physics, Bhavnagar University, Bhavnagar 364022 (India)

    2011-05-15

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe{sub 3}O{sub 4}-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe{sub 3}O{sub 4}) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 {mu}g/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients. - Research Highlights: Synthesis of Fe{sub 3}O{sub 4}-Ag core-shell nanocolloids. Antifungal activity of Fe{sub 3}O{sub 4}-Ag nanocolloids against Aspergillus glaucus isolates. The MIC value for A. glaucus is 2000 {mu}g/mL. Antifungal activity is better or comparable with most prominent antibiotics.

  9. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection.

    Science.gov (United States)

    Ferraz, Marcela L; Gazzinelli, Ricardo T; Alves, Rosana O; Urbina, Julio A; Romanha, Alvaro J

    2009-01-01

    We investigated the influence of CD4(+) T lymphocytes, CD8(+) T lymphocytes, and B lymphocytes on the efficacy of posaconazole (POS) and the reference drug benznidazole (BZ) during treatment of acute Trypanosoma cruzi infection in a murine model. Wild-type mice infected with T. cruzi and treated with POS or BZ presented no parasitemia, 100% survival, and 86 to 89% cure rates, defined as the percentages of animals with negative hemocultures at the end of the observation period. CD4(+)-T-lymphocyte-knockout (KO) mice infected with T. cruzi and treated with BZ or POS controlled parasitemia during treatment, although circulating parasites reappeared after drug pressure cessation, leading to only a 6% survival rate and no cure. CD8(+)-T-lymphocyte-KO mice infected with T. cruzi and treated with POS or BZ had intermediate results, displaying discrete parasitemia after the treatment was ended, 81 and 86% survival, and cure rates of 31 and 66%, respectively. B-lymphocyte-KO mice infected with T. cruzi and treated with BZ relapsed with parasitemia 1 week after the end of treatment and had a 67% survival rate and only a 22% cure rate. In contrast, the activity of POS was much less affected in these animals, with permanent suppression of parasitemia, 100% survival, and a 71% cure rate. Our results demonstrate that abrogation of different lymphocytes' activities has distinct effects on the efficacy of POS and BZ in this experimental model, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune system.

  10. Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit.

    Science.gov (United States)

    Watt, Kevin M; Cohen-Wolkowiez, Michael; Williams, Duane C; Bonadonna, Desiree K; Cheifetz, Ira M; Thakker, Dhiren; Benjamin, Daniel K; Brouwer, Kim L R

    2017-09-01

    Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood, and flow was set to 1 L/min. Drug was dosed to achieve therapeutic concentrations. Each antifungal was added to a separate tube of blood to serve as a control. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point: (C t /C i )*100, with C t and C i the concentrations at time = t and 1 minute, respectively. After 24 hours of recirculation, mean recovery of fluconazole in the ECMO circuit (95-98%) and controls (101%) was high. In contrast, mean recovery of micafungin was dependent on the time and circuit configuration. Recovery at 4 hours was only 46% when a hemofilter was in-line but was much higher when the hemofilter was removed (91%). By 24 hours, however, micafungin recovery was low in all circuit configurations (26-43%), regardless of the presence of a hemofilter, as well as in the controls (57%). In conclusion, these results suggest that micafungin is extracted by the ECMO circuit, which may result in decreased drug exposure in vivo.

  11. Antifungal activity of some tetranortriterpenoids.

    Science.gov (United States)

    Govindachari, T R; Suresh, G; Gopalakrishnan, G; Masilamani, S; Banumathi, B

    2000-06-01

    Natural tetranortriterpenoids such as cedrelone from Toona ciliata, azadiradione from Azadirachta indica, limonin, limonol and nomilinic acid from Citrus medica, along with some cedrelone derivatives were tested for their antifungal activity against Puccinia arachidis, a groundnut rust pathogen. Results show that cedrelone was the most effective in reducing rust pustule emergence. Replacement of functional groups or modification of the A or the B ring in cedrelone reduced the effectiveness indicating the importance of specific structural features for activity.

  12. 21 CFR 524.1610 - Orbifloxacin, mometasone furoate monohydrate, and posaconazole suspension.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL.... 000061 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. For dogs weighing less than 30 lbs. instill 4 drops once daily into the ear canal. For dogs weighing 30 lbs. or more, instill...

  13. The comparative study of antifungal activity of Syzygium aromaticum, Punica granatum and nystatin on Candida albicans; an in vitro study.

    Science.gov (United States)

    Mansourian, A; Boojarpour, N; Ashnagar, S; Momen Beitollahi, J; Shamshiri, A R

    2014-12-01

    Candida species are opportunistic fungi, among which, Candida albicans is the most important species responsible for infections in immunocompromised patients with invasive fungal disease. Resistance of Candida species to antifungal drugs has led scientists to pay more attention to traditional medicine herbs. Due to the limitations in the treatment of fungal diseases such as shortages, high prices, antifungal side effects and drug resistance or reduced susceptibility to fungal drugs we decided to study the antifungal effects of herbal extracts of Syzygium aromaticum and Punica granatum. Twenty-one isolates of oral C. albicans in patients with denture stomatitis referred to prosthesis department, Dental faculty of Tehran University of Medical Sciences were prepared and cultured. Plant extracts were prepared from the herbs market. Tests on patient samples and standard strains 5027ATCC (PTCC10231) yeast C. albicans were performed via well diffusion method. In addition, nystatin and methanol were used as positive and negative control, respectively. Finally, the antifungal effect of extracts using Statistical Repeated measurement ANOVA test was investigated. Both S. aromaticum and P. granatum showed noticeable antifungal activity in well method. Syzygium aromaticum showed better anti candida activity than nystatin (Pgranatum showed good antifungal effects (P-value<0.001). S. aromaticum (inhibition zone diameter: 29.62) showed better antifungal effects than nystatin (inhibition zone diameter: 28.48). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Antifungal activity of topical microemulsion containing a thiophene derivative

    Directory of Open Access Journals (Sweden)

    Geovani Pereira Guimarães

    2014-06-01

    Full Text Available Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05 embedded in a microemulsion (ME. The minimum inhibitory concentration (MIC was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05 showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1 and good activity against C. neoformans (MIC = 17 µg.mL-1. Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1, but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

  15. Antifungal potential of marine natural products

    OpenAIRE

    El-Hossary, Ebaa M.; Cheng, Cheng; Hamed, Mostafa M.; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan

    2017-01-01

    Highlights: • Fungal infections represent an increasing threat to human health. • Fungal infections in plants are a worldwide problem to the agricultural industry. • Diverse antifungal compounds were isolated from different marine organisms. • The number of new antifungal marine natural products is rapidly developing. • Marine sponges and bacteria are the predominant sources for antifungal compounds. Abstract: Fungal diseases represent an increasing threat to human healt...

  16. [Zygomycetes and zygomycosis in the new era of antifungal therapies].

    Science.gov (United States)

    Torres-Narbona, M; Guinea, J; Muñoz, P; Bouza, E

    2007-12-01

    Zygomycosis or mucormycosis is the third most invasive fungal infection after candidiasis and aspergillosis. Traditionally, it has been considered a community-acquired disease, but it is becoming a frequent nosocomial-acquired disease. Recently, several publications from different institutions have reported an increase in the number of cases of invasive zygomycosis as a result of the new antifungal and immunosuppresive therapies and the emerging immunocompromised population. In addition, the diagnosis of zygomycosis is elusive, mainly in pulmonary and disseminated forms. One of the main limitations in isolating Zygomycetes from clinical samples is the interpretation of results. The increasing number of invasive fungal infections caused by multiresistant fungi has led to the development of new antifungal drugs with variable activity against Zygomycetes.

  17. Synthesis, Anti-Bacterial and Anti-Fungal Evaluation of Pyrazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Ashvin D. Panchal

    2012-01-01

    Full Text Available The Series of N-(5-(Substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine compounds were prepared by reaction of 4-amino-1,2,4-Triazole with Acetyl Chloride followed by different aromatic aldehydes and cyclization with hydrazine hydrate. The structures of new compounds were confirmed by IR and 1H-NMR spectral data. Anti-bacterial and Anti-fungal activities were evaluated and compared with the standard drugs, some compounds of the series exhibited promising anti-microbial and anti-fungal activity compared to standard drugs.

  18. Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

    Science.gov (United States)

    Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

    2016-01-01

    Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

  19. Antifungal effects of Allium ascalonicum, Marticaria chamomilla and Stachys lavandulifolia extracts on Candida albicans

    Directory of Open Access Journals (Sweden)

    Moghim Hassan

    2014-01-01

    Full Text Available Introduction: Due to increased risk for opportunistic fungal infections and increasing prevalence of hospital infections caused by pathogenic yeasts and fungus resistance to antifungal drugs, discovery of antifungal compounds with high efficiency is necessary. This study was aimed to evaluate and compare the antifungal activities of Allium ascalonicum, Marticaria chamomilla and Stachys lavandulifolia on Candida albians. Methods: In this study the plants extracts were prepared with macerated method using ethanol 70%. Antifungal activities of the extracts were performed according to microbroth dilution method in 96 well microdilution plates. The amount of Minimum Inhibitory Concentration (MIC and Minimum Fungicidal Concentration (MFC based on counting the number of fungal colonies (CFU were evaluated for each of Allium ascalonicum, Chamomile and Stachys lavandulifolia extracts compared with the control group. Results: MIC of Allium ascalonicum, Marticaria chamomilla and Stachys lavandulifolia were respectively 0.31, 3.75 and 15.13 mg/ml and also MIC50% of Allium ascalonicum, Marticaria chamomilla and Stachys lavandulifolia were respectively 0.93, 10.59 and 41.32 mg/ml and MIC 90% of them were respectively 8.65, 16.88 and 60.55 mg/ml and their MFC were respectively 20, 20 and 65 mg/ml. Conclusion: The results indicate that all three extracts are effective, but Allium ascalonicum possesses the highest antifungal activity on Candida albicans. If clinical trials approve these findings, this plant may represent a new source of antifungal agent for control of Candida albicans.

  20. Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils

    Directory of Open Access Journals (Sweden)

    MARIA E.A. PINTO

    2017-08-01

    Full Text Available ABSTRACT Fatty acid methyl esters (FAMEs were obtained from vegetable oils of soybean, corn and sunflower. The current study was focused on evaluating the antifungal activity of FAMEs mainly against Paracoccidioides spp., as well as testing the interaction of these compounds with commercial antifungal drugs and also their antioxidant potential. FAMEs presented small IC50 values (1.86-9.42 μg/mL. All three FAMEs tested showed antifungal activity against isolates of Paracoccidioides spp. with MIC values ranging from 15.6-500 µg/mL. Sunflower FAMEs exhibited antifungal activity that extended also to other genera, with an MIC of 15.6 μg/mL against Candida glabrata and C. krusei and 31.2 μg/mL against C. parapsilosis. FAMEs exhibited a synergetic effect with itraconazole. The antifungal activity of the FAMEs against isolates of Paracoccidioides spp. is likely due to the presence of methyl linoleate, the major compound present in all three FAMEs. The results obtained indicate the potential of FAMEs as sources for antifungal and antioxidant activity.

  1. Parasiticidal, antifungal and antibacterial activities of Onosma ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... neubauer counting chamber and IC50 values of compounds pos- sessing antileishmanial activity were calculated by Software Ezfit. 5.03 Perella Scientific. IC50 values of different fractions against the test pathogen are mentioned in Table 1. Antifungal activity. Similarly antifungal activity was evaluated by ...

  2. INVESTIGATION OF ANTIFUNGAL ACTIVITY OF QUINOLINIUM DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. A. Alexandrova

    2013-01-01

    Full Text Available Abstract. Antifungal activity (Candida albicans, Candida krusei of some substituted quinolinium derivatives has been investigated. It was established that the most perspective compound for detail investigation of antifungal activity by labeled biomarkers method was N-phenylbenzoquinaldinium tetrafluoroborate.

  3. Correlation between Plant Secondary Metabolites and Their Antifungal Mechanisms–A Review

    DEFF Research Database (Denmark)

    Freiesleben, Sara; Jäger, Anna

    2014-01-01

    The search for new antifungal drugs often involves secondary metabolites from plants because of their pharmacological activity against foreign pathogens. Among the modern drugs in use today about 40% are of natural origin. To distinguish the secondary metabolites they can be divided into groups...... search for existing knowledge about antifungal mechanisms of different secondary metabolites from plants. The secondary metabolites have been grouped into three major groups according to their biosynthetic origin, and into subgroups according to their structure. There seems to be a correlation between...... biosynthetic groups of secondary metabolites; the phenolic compounds and the nitrogen containing compounds. Despite this there are correlations between some of the subgroups and their antifungal mechanism of actions....

  4. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Directory of Open Access Journals (Sweden)

    Rodrigo Almeida-Paes

    Full Text Available Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC and minimal fungicidal concentrations (MFC of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  5. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  6. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs

    DEFF Research Database (Denmark)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V

    2016-01-01

    of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along...

  7. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase.

    Science.gov (United States)

    Bojsen, Rasmus; Regenberg, Birgitte; Folkesson, Anders

    2014-12-04

    Biofilm-forming Candida species cause infections that can be difficult to eradicate, possibly because of antifungal drug tolerance mechanisms specific to biofilms. In spite of decades of research, the connection between biofilm and drug tolerance is not fully understood. We used Saccharomyces cerevisiae as a model for drug susceptibility of yeast biofilms. Confocal laser scanning microscopy showed that S. cerevisiae and C. glabrata form similarly structured biofilms and that the viable cell numbers were significantly reduced by treatment of mature biofilms with amphotericin B but not voriconazole, flucytosine, or caspofungin. We showed that metabolic activity in yeast biofilm cells decreased with time, as visualized by FUN-1 staining, and mature, 48-hour biofilms contained cells with slow metabolism and limited growth. Time-kill studies showed that in exponentially growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response of growing biofilms to antifungal drugs was similar to the response of exponentially growing planktonic cells. The response in mature biofilm was similar to that of non-growing planktonic cells. These results confirmed the importance of growth phase on drug efficacy. We showed that in vitro susceptibility to antifungal drugs was independent of biofilm or planktonic growth mode. Instead, drug tolerance was a consequence of growth arrest achievable by both planktonic and biofilm populations. Our results suggest that efficient strategies for treatment of yeast biofilm might be developed by targeting of non-dividing cells.

  8. Correlation between Plant Secondary Metabolites and Their Antifungal Mechanisms–A Review

    DEFF Research Database (Denmark)

    Freiesleben, Sara; Jäger, Anna

    2014-01-01

    The search for new antifungal drugs often involves secondary metabolites from plants because of their pharmacological activity against foreign pathogens. Among the modern drugs in use today about 40% are of natural origin. To distinguish the secondary metabolites they can be divided into groups b...... biosynthetic groups of secondary metabolites; the phenolic compounds and the nitrogen containing compounds. Despite this there are correlations between some of the subgroups and their antifungal mechanism of actions....... it is interesting to investigate a relation between the biosynthetic origin of the antifungal compound and it’s mode of action against fungi. This correlation could limit the search to those natural compounds, which only interferes with the target of interest. This review is based on a comprehensive literature...... the biosynthetic group of terpenes and their antifungal mechanisms of action, all of them exhibiting their antifungal action through cell membrane disruption, although some of the terpenes also seemed to work through mitochondrial dysfunction. A clear correlation has not been demonstrated between the two other...

  9. Determination of antifungal susceptibility patterns among the clinical isolates of Candida species

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    Kamiar Zomorodian

    2011-01-01

    Full Text Available Context: Candida species are opportunistic yeasts that cause infections ranging from simple dermatosis to potentially life-threatening fungemia. The emergence of resistance to antifungal drugs has been increased in the past two decades. Aim: the present study we determined to find out the susceptibility profiles of clinical isolates of Candida species against four antifungal drugs, including amphotericin B, ketoconazole, fluconazole and itraconazole. Materials and Methods: Antifungal susceptibility testing of the yeasts was done in accordance with the proposed guidelines for antifungal disk diffusion susceptibility testing of yeasts based on the CLSI document M44-A. Results: A total of 206 yeast isolates were assessed. Among the evaluated Candida species, the highest rates of resistance to ketoconazole were seen in Candida glabrata (16.6% and Candida albicans (3.2%. Susceptibility and intermediate response to fluconazole were seen in 96.6% and 3.4% of the Candida isolates, respectively. A total of 19 (9.2% yeast isolates showed petite phenomenon including 11 C. glabrata, 3 C. albicans, 2 Candida dubliniensis and one isolate of each Candida krusei and Candida parapsilosis. Conclusion: The high number of petite mutation in the isolated yeasts should be seriously considered since it may be one of the reasons of antifungal treatment failure.

  10. Comparing antifungal effects of Zatariamultiflora and Punicagranatum extract with Nystatin on Candida Albicans

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    F. Nouri

    2016-12-01

    Full Text Available Background: Despite all the progress that has been made in the manufacture of synthetic drugs, herbal drugs are increasingly taken into account. This is due to the growing belief that they have fewer side effects compared to synthetic ones. Objective: To compare the antifungal effects of extracts of Zatariamultiflora and Punicagranatum with Nystatin on Candida Albicans. Methods: This inviro trial accomplished in the school of dentistry of Tehran University in 2012. From the mouths of 25 patients with denture stomatitis were sampled using sterile swabs. Candida Albicans strains were isolated from samples and standard Candida Albicans PTCC 5027 were cultured too. Then extract of Zatariamultiflora and Punicagranatum to be obtained and antifungal of extract studied with disk diffusion method. Antifungal power of each of the extracts on the inhibition zone diameter was created in the medium. Data were analyzed by ANOVA and Friedman statistical tests. Findings: Results showed extracts of Zataria and pomegranate flowers have antifungal significant effects (P<0.001. Diameter of inhabitation zone was 17.66±./75 mm in Nystatin group and in the Zataria and pomegranate flowers extracts groups was lower (P<0.001. None of the negative control disc did inhibition zone in the medium. Conclusion: With due attention of Zataria and pomegranate flowers extracts exhibited antifungal effects on Candida Albincans.

  11. Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates.

    Science.gov (United States)

    Badiee, Parisa; Badali, Hamid; Boekhout, Teun; Diba, Kambiz; Moghadam, Abdolkarim Ghadimi; Hossaini Nasab, Ali; Jafarian, Hadis; Mohammadi, Rasoul; Mirhendi, Hossein; Najafzadeh, Mohammad Javad; Shamsizadeh, Ahmad; Soltani, Jafar

    2017-11-21

    Antifungal susceptibility testing is a subject of interest in the field of medical mycology. The aim of the present study were the distributions and antifungal susceptibility patterns of various Candida species isolated from colonized and infected immunocompromised patients admitted to ten university hospitals in Iran. In totally, 846 Candida species were isolated from more than 4000 clinical samples and identified by the API 20 C AUX system. Antifungal susceptibility testing was performed by broth microdilution method according to CLSI. The most frequent Candida species isolated from all patients was Candida albicans (510/846). The epidemiological cutoff value and percentage of wild-type species for amphotericin B and fluconazole in Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were 0.5 μg/ml (95%) and 4 μg/ml (96%); 1 μg/ml (95%) and 8 μg/ml (95%); 0.5 μg/ml (99%) and 19 μg/ml (98%); and 4 μg/ml (95%) and 64 μg/ml (95%), respectively. The MIC90 and epidemiological cutoff values to posaconazole in Candida krusei were 0.5 μg/ml. There were significant differences between infecting and colonizing isolates of Candida tropicalis in MIC 90 values of amphotericin B, and isolates of Candida glabrata in values of amphotericin B, caspofungin, and voriconazole (P Candida species (colonizing and infecting isolates) in immunocompromised patients are not the same and acquired resistance was seen in some species.

  12. Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates

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    Parisa Badiee

    2017-11-01

    Full Text Available Abstract Background Antifungal susceptibility testing is a subject of interest in the field of medical mycology. The aim of the present study were the distributions and antifungal susceptibility patterns of various Candida species isolated from colonized and infected immunocompromised patients admitted to ten university hospitals in Iran. Methods In totally, 846 Candida species were isolated from more than 4000 clinical samples and identified by the API 20 C AUX system. Antifungal susceptibility testing was performed by broth microdilution method according to CLSI. Results The most frequent Candida species isolated from all patients was Candida albicans (510/846. The epidemiological cutoff value and percentage of wild-type species for amphotericin B and fluconazole in Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were 0.5 μg/ml (95% and 4 μg/ml (96%; 1 μg/ml (95% and 8 μg/ml (95%; 0.5 μg/ml (99% and 19 μg/ml (98%; and 4 μg/ml (95% and 64 μg/ml (95%, respectively. The MIC90 and epidemiological cutoff values to posaconazole in Candida krusei were 0.5 μg/ml. There were significant differences between infecting and colonizing isolates of Candida tropicalis in MIC 90 values of amphotericin B, and isolates of Candida glabrata in values of amphotericin B, caspofungin, and voriconazole (P < 0.05. Conclusions Our findings suggest that the susceptibility patterns of Candida species (colonizing and infecting isolates in immunocompromised patients are not the same and acquired resistance was seen in some species.

  13. Bibliometric analysis of literature on antifungal triazole resistance: 1980 - 2015.

    Science.gov (United States)

    Sweileh, Waleed M; Sawalha, Ansam F; Al-Jabi, Samah; Zyoud, Sa'ed H

    2017-03-01

    Triazole antifungal agents play an important role in the treatment of a wide range of fungal infections. Little is known about antifungal triazole drug resistance when compared to antibiotic resistance. Therefore, this study was carried out to give a bibliometric overview of literature on triazole antifungal drug resistance. Keywords related to triazole drug class and resistance were used in a search query in the Scopus search engine. The time span was set from 1980 to 2015. Data pertaining to growth of publications, the most active countries and institutions, the most cited articles, and mapping of molecular mechanisms of resistance were analyzed. A total of 1648 journal articles were retrieved with an average of 20.46 citations per article. Annual growth of triazole resistance showed an increasing pattern during the study period. The United States of America (n=446; 27.06%) ranked first in productivity followed by the United Kingdom (UK) (n=176; 10.68%), and China (n=133; 8.07%). Radboud University Nijmegen Medical Centre (n=69, 4.19%) in the Netherlands ranked first in productivity, while the journal Antimicrobial Agents and Chemotherapy ranked first (n=255; 15.47%) in publishing articles on triazole resistance. Mapping mechanisms of resistance showed that efflux pump and mutations in target enzyme are major mechanisms described in resistance to triazoles. There was a growth of publications on triazole resistance in the past two decades with the bulk of publications on triazole resistance in Candida species. The data presented here will serve as baseline information for future comparative purposes.

  14. Probiotics as Antifungals in Mucosal Candidiasis.

    Science.gov (United States)

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital

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    Vazin A

    2015-06-01

    Full Text Available Afsaneh Vazin,1 Mohammad Ali Davarpanah,2 Setareh Ghalesoltani3 1Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2HIV Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3International Branch of Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Abstract: To evaluate pattern of using of three antifungal drugs: fluconazole, amphotericin B and voriconazole, at the hematology–oncology and bone marrow transplant wards of one large teaching hospital. In a prospective cross-sectional study, we evaluated the appropriateness of using antifungal drugs in patients, using Infectious Disease Society of America (IDSA and National Comprehensive Cancer Network (NCCN guidelines. All the data were recorded daily by a pharmacist in a form designed by a clinical pharmacist and infectious diseases specialist, for antifungals usage, administration, and monitoring. During the study, 116 patients were enrolled. Indications of prescribing amphotericin B, fluconazole, and voriconazole were appropriate according to guidelines in 83.4%, 80.6%, and 76.9% respectively. The duration of treatments were appropriate according to guidelines in 75%, 64.5%, and 71.1% respectively. The dose of voriconazole was appropriate according to guidelines in 46.2% of patients. None of the patients received salt loading before administration of amphotericin B. The most considerable problems with the mentioned antifungals were about the indications and duration of treatment. In addition, prehydration for amphotericin B and dosage of voriconazole were not completely compatible with the mentioned guidelines. A suitable combination of controlling the use of antifungals and educational programs could be essential for improving the general process of using antifungal drugs at our hospital. Keywords: utilization evaluation, fluconazole, amphotericin B, voriconazole, neutropenia

  16. Discovery of a Novel Dibromoquinoline Compound Exhibiting Potent Antifungal and Antivirulence Activity That Targets Metal Ion Homeostasis.

    Science.gov (United States)

    Mohammad, Haroon; Elghazawy, Nehal H; Eldesouky, Hassan E; Hegazy, Youssef A; Younis, Waleed; Avrimova, Larisa; Hazbun, Tony; Arafa, Reem K; Seleem, Mohamed N

    2018-03-09

    Globally, invasive fungal infections pose a significant challenge to modern human medicine due to the limited number of antifungal drugs and the rise in resistance to current antifungal agents. A vast majority of invasive fungal infections are caused by species of Candida, Cryptococcus, and Aspergillus. Novel antifungal molecules consisting of unexploited chemical scaffolds with a unique mechanism are a pressing need. The present study identifies a dibromoquinoline compound (4b) with broad-spectrum antifungal activity that inhibits the growth of pertinent species of Candida (chiefly C. albicans), Cryptococcus, and Aspergillus at a concentration of as low as 0.5 μg/mL. Furthermore, 4b, at a subinhibitory concentration, interfered with the expression of two key virulence factors (hyphae and biofilm formation) involved in C. albicans pathogenesis. Three yeast deletion strains ( cox17Δ, ssa1Δ, and aft2Δ) related to metal ion homeostasis were found to be highly sensitive to 4b in growth assays, indicating that the compound exerts its antifungal effect through a unique, previously unexploited mechanism. Supplementing the media with either copper or iron ions reversed the strain sensitivity to 4b, further corroborating that the compound targets metal ion homeostasis. 4b's potent antifungal activity was validated in vivo, as the compound enhanced the survival of Caenorhabditis elegans infected with fluconazole-resistant C. albicans. The present study indicates that 4b warrants further investigation as a novel antifungal agent.

  17. In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

    Science.gov (United States)

    Galgóczy, L; Tóth, Liliána; Virágh, M; Papp, T; Vágvölgyi, C S

    2012-12-01

    The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

  18. Antifungal isopimaranes from Hypoestes serpens.

    Science.gov (United States)

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis.

  19. Antifungal activity of essential oils of Origanum vulgare and Rosmarinus officinalis against three Candida albicans strains

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    Delić Dafina N.

    2013-01-01

    Full Text Available Due to general growing resistance and side effects to common antifungal drugs nowadays, there have been many studies reported on the use of herbal essential oils as antifungal agents in recent years. In this study, essential oils of Origanum vulgare and Rosmarinus officinalis (Lamiaceae were examined for their in vitro antifungal activity against three Candida albicans strains (laboratory - CAL, human pulmonary - CAH, and reference ATCC10231-CAR in comparison to Nystatin (0.30 mg/ml and Fluconazole (2 mg/ml as standard antifungal agents. The antifungal activity was evaluated by comparing inhibition zone diameters obtained both by disc-and well-diffusion assays, as well as by comparing MIC and MBC values detected by microdilution assay. Diffusion test results revealed stronger antifungal effect of O. vulgare against all analyzed C. albicans strains identifying CAL strain as the most susceptible one. Inhibition zones ranged from 12.65 to 25.10 mm depending on the concentrations applied. The highest concentrations of Rosemary essential oil (5.00 mg/ml demonstrated activity against two strains: CAL and CAR ATCC 10231 in both diffusion assays applied, while no antifungal activity was recorded against CAH isolate. Microdilution assay showed that both oils demonstrated the same MIC values for all tested strains (0.11 mg/ml, except MIC value against ATCC strain (0.23 mg/ml obtained for Rosemary essential oil. The obtained results indicated that oregano and rosemary essential oils might be highly effective in the natural prevention treatment of candidiasis, although toxicity assays should be previously preformed. [Projekat Ministarstva nauke Republike Srbije, br. 172058

  20. Risk of serious skin disorders among users of oral antifungals: a population-based study

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    Duque Alberto

    2002-11-01

    Full Text Available Abstract Background Serious skin disorders have been associated with the use of oral antifungals in a number of case reports and series of cases. However the incidence of these disorders remains unknown. Methods We estimated the risk of serious skin disorders in a cohort of users of oral antifungals identified in the general population of the General Practice Research Database in the UK. The cohort included 61,858 patients, 20 to 79 years old, who had received at least one prescription for either oral fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine. Results The background rate of serious cutaneous adverse reactions (the one corresponding to non use of oral antifungals was 3.9 per 10,000 person-years (95% CI 2.9–5.2. Incidence rates for current use were 15.4 per 10,000 person-years (1.9–55.7 for itraconazole, 11.1 (3.0–28.5 for terbinafine, 10.4 (1.3–37.5 for fluconazole, and 4.6 (0.1–25.8 for griseofulvin. Itraconazole was the antifungal associated with the highest relative risk, 3.9 (0.5–15.0, when compared to the risk among non users, followed by terbinafine and fluconazole, with relative risks of 2.8 (0.7–7.8 and 2.6 (0.3–10.1, respectively. Conclusions We conclude that cutaneous disorders associated with the use of oral antifungals in this study were all of mild severity and that the risk associated with the use of oral antifungals was slightly higher than the risk in non-users. The safety profile of terbinafine regarding cutaneous disorders is similar to other antifungals and in the very low range of risks associated with other drugs.

  1. Evaluation of the post-antifungal effect (PAFE) of amphotericin B and nystatin against 30 zygomycetes using two different media.

    NARCIS (Netherlands)

    Vitale, R.G.; Meis, J.F.G.M.; Mouton, J.W.; Verweij, P.E.

    2003-01-01

    The post-antifungal effect (PAFE) of amphotericin B and nystatin against 30 clinical zygomycetes was evaluated using two different media. PAFE is a suppression of fungal growth after limited drug exposure. The MICs of both drugs were determined using NCCLS M38-P guidelines. A spectrophotometric

  2. Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells

    Science.gov (United States)

    Kim, Nayoung; Choi, Ji-Wan; Park, Hye-Ran; Kim, Inki; Kim, Hun Sik

    2017-01-01

    Immunomodulatory drugs (IMiDs) present one example of immunomodulatory agents that improve cancer immunotherapy. Based on the cytotoxic activity of natural killer (NK) cells against cancer cells, a high throughput screening method for the identification of novel immunomodulatory molecules with the potential to stimulate NK cell cytotoxicity against cancer cells was designed and tested using an approved drug library. Among the primary hit compounds, the anti-fungal drug amphotericin B (AMP-B) increased the cytotoxicity of NK cell line and human primary NK cells in a direct manner. The increase in NK cell activity was related to increased formation of NK-target cell conjugates and the subsequent granule polarization toward target cells. The results of the present study indicate that AMP-B could serve a dual function as an anti-fungal and immunomodulatory drug. PMID:28608807

  3. Production, optimization, characterization and antifungal activity of ...

    African Journals Online (AJOL)

    SAM

    2014-04-02

    Apr 2, 2014 ... the present study, the antifungal activity of crude A. terrus chitinase was investigated against Apergillus niger, Aspergillus oryzae .... Chitinase activity was determined spectrophotometrically by estimating the amount of ..... characterization of two. Bifunctional chitinases lysozyme extracellularly produced by.

  4. In vitro antifungal activities of leaf extracts of Lippia alba (Verbenaceae against clinically important yeast species

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    Graziela Teixeira de Oliveira

    2014-04-01

    Full Text Available Introduction There are few studies reporting the antifungal activities of Lippia alba extracts. Methods A broth microdilution assay was used to evaluate the antifungal effects of Lippia alba extracts against seven yeast species of Candida and Cryptococcus. The butanol fraction was investigated by gas chromatography-mass spectrometry. Results The butanol fraction showed the highest activity against Candida glabrata. The fraction also acted synergistically with itraconazole and fluconazole against C. glabrata. The dominant compounds in the butanol fraction were 2,2,5-trimethyl-3,4-hexanedione, 3,5-dimethyl-4-octanone and hexadecane. Conclusions The butanol fraction may be a good candidate in the search for new drugs from natural products with antifungal activity.

  5. Conazoles

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    Jan Heeres

    2010-06-01

    Full Text Available This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described.

  6. Propolis from the northwest of Argentina as a source of antifungal principles.

    Science.gov (United States)

    Quiroga, E N; Sampietro, D A; Soberón, J R; Sgariglia, M A; Vattuone, M A

    2006-07-01

    To determine the antimycotic and cytotoxic activities of partially purified propolis extract on yeasts, xylophagous and phytopathogenic fungi. To compare these activities with pinocembrin and galangin isolated from this propolis and with the synthetic drugs ketoconazole and clortrimazole. Ethanolic propolis extract was partially purified by cooling at -20 degrees C. Two of its components were isolated by HPLC and identified as pinocembrin and galangin. The antifungal activity was assayed by bioautography, hyphal radial growth, hyphal extent and microdilution in liquid medium. Cytotoxicity was studied with the lethality assay of Artemia salina. The obtained results were compared with the actions of ketoconazole and clortrimazole. The results showed that the antifungal potency of ketoconazole and clortrimazole is higher than pinocembrin, galangin and the partially purified propolis extract in this order. Otherwise, the cytotoxicity of the synthetic drugs is also the highest. Partially purified propolis extract inhibits fungal growth. The comparison of its relative biocide potency and cytotoxicity with synthetic drugs and two components of this propolis (pinocembrin and galangin) showed that the propolis from 'El Siambón', Tucumán, Argentina, is a suitable source of antifungal products. The partially purified propolis extract and its isolated compounds, pinocembrin and galangin, have the capacity of being used as antifungals without detriment to the equilibrium of agroecosystems. The impact of this study is that the preparation of agrochemicals with reduced economic costs using a partially purified preparation as the active principle is possible.

  7. Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

    Science.gov (United States)

    Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

    2014-01-01

    Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

  8. Enhanced Antifungal Activity by Ab-Modified Amphotericin B-Loaded Nanoparticles Using a pH-Responsive Block Copolymer

    Science.gov (United States)

    Tang, Xiaolong; Dai, Jingjing; Xie, Jun; Zhu, Yongqiang; Zhu, Ming; Wang, Zhi; Xie, Chunmei; Yao, Aixia; Liu, Tingting; Wang, Xiaoyu; Chen, Li; Jiang, Qinglin; Wang, Shulei; Liang, Yong; Xu, Congjing

    2015-06-01

    Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Amphotericin B (AMB), with broad-spectrum antifungal activity, has long been recognized as a powerful fungicidal drug, but its clinical toxicities mainly nephrotoxicity and poor solubility limit its wide application in clinical practice. The fungal metabolism along with the host immune response usually generates acidity at sites of infection, resulting in loss of AMB activity in a pH-dependent manner. Herein, we developed pH-responsive AMB-loaded and surface charge-switching poly( d, l-lactic- co-glycolic acid)- b-poly( l-histidine)- b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for resolving the localized acidity problem and enhance the antifungal efficacy of AMB. Moreover, we modified AMB-encapsulated PLGA-PLH-PEG nanoparticles with anti- Candida albicans antibody (CDA) (CDA-AMB-NPs) to increase the targetability. Then, CDA-AMB-NPs were characterized in terms of physical characteristics, in vitro drug release, stability, drug encapsulation efficiency, and toxicity. Finally, the targetability and antifungal activity of CDA-AMB-NPs were investigated in vitro /in vivo. The result demonstrated that CDA-AMB-NPs significantly improve the targetability and bioavailability of AMB and thus improve its antifungal activity and reduce its toxicity. These NPs may become a good drug carrier for antifungal treatment.

  9. Evaluation of antifungal activity of standardized extract of Salvia rhytidea Benth. (Lamiaceae) against various Candida isolates.

    Science.gov (United States)

    Salari, S; Bakhshi, T; Sharififar, F; Naseri, A; Ghasemi Nejad Almani, P

    2016-12-01

    Salvia species have long been described in traditional medicine for various indications. Owing to the widespread use of this genus by ethnic populations, especially for various infections ranging from skin disease to gastrointestinal disorders, we were encouraged to determine whether Salvia rhytidea could be effective against fungal infections. Given the increased incidence of candidiasis in the past decade, limits on the use of antifungal drugs, emergence of azole-resistant Candida species and increased incidence of treatment failures, it is necessary to identify a novel agent with antifungal properties. Aim of the study was to evaluate the antifungal properties of S. rhytidea against various Candida isolates. In this study, at first rosmarinic acid content of plant extract was determined. A total of 96 Candida isolates were tested, including the following species: Candida albicans (n=42), Candida glabrata (n=16), Candida tropicalis (n=11), Candida krusei (n=9), Candida parapsilosis (n=9), Candida lusitaniae (n=7) and Candida guilliermondii (n=2). The in vitro antifungal activity of methanolic extracts of S. rhytidea Benth. was evaluated against Candida isolates and compared with that of the standard antifungal drug nystatin by using a broth microdilution method, according to CLSI. Phytochemical screening results showed that the methanolic extract of S. rhytidea Benth. was rich in flavonoids and tannins. The minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of S. rhytidea Benth. ranged from 3.125 to>100μg/ml and 6.25 to>100μg/ml respectively. The growth inhibition value displayed that C. tropicalis, C. krusei and C. albicans isolates were most susceptible to S. rhytidea. Findings show that S. rhytidea possesses an antifungal effect against Candida isolates. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    Directory of Open Access Journals (Sweden)

    Mahoney Noreen

    2011-05-01

    Full Text Available Abstract Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI. Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ and two mitogen-activated protein kinase (MAPK mutants of A. fumigatus (sakAΔ, mpkCΔ, indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC or fungicidal (MFC

  11. AMDD: Antimicrobial Drug Database

    OpenAIRE

    Danishuddin, Mohd; Kaushal, Lalima; Hassan Baig, Mohd; Khan, Asad U.

    2012-01-01

    Drug resistance is one of the major concerns for antimicrobial chemotherapy against any particular target. Knowledge of the primary structure of antimicrobial agents and their activities is essential for rational drug design. Thus, we developed a comprehensive database, anti microbial drug database (AMDD), of known synthetic antibacterial and antifungal compounds that were extracted from the available literature and other chemical databases, e.g., PubChem, PubChem BioAssay and ZINC, etc. The ...

  12. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents.

    Science.gov (United States)

    Kim, Jong H; Campbell, Bruce C; Mahoney, Noreen; Chan, Kathleen L; Molyneux, Russell J; Balajee, Arunmozhi

    2010-10-01

    A number of benzoic acid analogues showed antifungal activity against strains of Aspergillus flavus, Aspergillus fumigatus and Aspergillus terreus, causative agents of human aspergillosis, in in vitro bioassays. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased by addition of a methyl, methoxyl or chloro group at position 4 of the aromatic ring, or by esterification of the carboxylic acid with an alkyl group, respectively. Thymol, a natural phenolic compound, was a potent chemosensitizing agent when co-applied with the antifungal azole drugs fluconazole and ketoconazole. The thymol-azole drug combination demonstrated complete inhibition of fungal growth at dosages far lower than the drugs alone. Co-application of thymol with amphotericin B had an additive effect on all strains of aspergilli tested with the exception of two of three strains of A. terreus, where there was an antagonistic effect. Use of two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus, sakAΔ and mpkCΔ, having gene deletions in the oxidative stress response pathway, indicated antifungal and/or chemosensitization activity of the benzo analogues was by disruption of the oxidative stress response system. Results showed that both these genes play overlapping roles in the MAPK system in this fungus. The potential of safe, natural compounds or analogues to serve as chemosensitizing agents to enhance efficacy of commercial antifungal agents is discussed. Published by Elsevier Ltd.

  13. Evaluation of semisolid agar method for antifungal susceptibility test of T. rubrum

    Directory of Open Access Journals (Sweden)

    Sultana Razia

    2016-08-01

    Full Text Available Background: With increasing fungal disease many newer antifungal drugs are available with different spectrum of activ­ity. Antifungal susceptibility test will help clinicians for selection of effective drug and thereby treatment of patient. Objective: The study was undertaken to perform a simple screening drug susceptibility test of T. rnbrum by Semi Solid Agar Antifungal Susceptibility (SAAS Method: Perfonnance of susceptibility method was assessed by comparing the MICs of three commonly prescribed antifungal agents namely- tluconazole (FCZ, itraconazole (ITZ and terbinafine (TER to the CLSI (Clinical and Laboratory Standard Institute recommended M-38, a broth microdilution method. Results: In SAAS method, among twenty nine T. rubrum, twenty five (86.2% were susceptible (MIC range 0.5-64 µg/ml to Fluconazole (FCZ and four (13.7% were resistant (MIC value >64 µg/ml. In broth microdilution method, among twenty nine T. rubrum, twenty six (89.6% were susceptible (MIC range 0.3-64 µg/ml to FCZ and three (10.3% were resistant (MIC value >64 µg/ml. In case of both ITZ and TER, all were susceptible (MIC range 0.3-64 µg/ml to both methods. The SAAS method demonstrated the susceptibility pattern of T. rubrum against FCZ, ITZ and TER usually within 72 to 96 hours after organism isolation and results were concordance with the results of CLSI broth microdilution method. Conclusion: Though it is a newer method with proper standardization of the test method, SAAS method is simple and easily applicable screening method for susceptibility testing of antifungal agents against dermatophytes in any microbiology laboratories.

  14. Impact of First-Line Antifungal Agents on the Outcomes and Costs of Candidemia

    Science.gov (United States)

    Ha, Young Eun; Joo, Eun-Jeong; Kim, Shin Woo; Jung, Sook-In; Chang, Hyun Ha; Park, Kyong Hwa; Han, Sang Hoon

    2012-01-01

    Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia. PMID:22526315

  15. The in vitro antifungal activity of sudanese medicinal plants against Madurella mycetomatis, the eumycetoma major causative agent.

    Directory of Open Access Journals (Sweden)

    Hassabelrasoul Elfadil

    2015-03-01

    Full Text Available Eumycetoma is a debilitating chronic inflammatory fungal infection that exists worldwide but it is endemic in many tropical and subtropical regions. The major causative organism is the fungus Madurella mycetomatis. The current treatment of eumycetoma is suboptimal and characterized by low cure rate and high recurrence rates. Hence, an alternative therapy is needed to address this. Here we determined the antifungal activity of seven Sudanese medicinal plant species against Madurella mycetomatis. Of these, only three species; Boswellia papyrifera, Acacia nubica and Nigella sativa, showed some antifungal activity against M. mycetomatis and were further studied. Crude methanol, hexane and defatted methanol extracts of these species were tested for their antifungal activity. B. papyrifera had the highest antifungal activity (MIC50 of 1 ug/ml and it was further fractionated. The crude methanol and the soluble ethyl acetate fractions of B. papyrifera showed some antifungal activity. The Gas-Liquid-Chromatography hybrid Mass-Spectrophotometer analysis of these two fractions showed the existence of beta-amyrin, beta-amyrone, beta-Sitosterol and stigmatriene. Stigmatriene had the best antifungal activity, compared to other three phytoconstituents, with an MIC-50 of 32 μg/ml. Although the antifungal activity of the identified phytoconstituents was only limited, the antifungal activity of the complete extracts is more promising, indicating synergism. Furthermore these plant extracts are also known to have anti-inflammatory activity and can stimulate wound-healing; characteristics which might also be of great value in the development of novel therapeutic drugs for this chronic inflammatory disease. Therefore further exploration of these plant species in the treatment of mycetoma is encouraging.

  16. In-vitro activity of commonly used antifungal agents in the presence of rifampin, polymyxin B and norfloxacin against Candida albicans.

    Science.gov (United States)

    Moneib, N A

    1995-12-01

    This study assessed the in-vitro antifungal activity against Candida albicans of amphotericin B, ketoconazole and miconazole, each in the presence of rifampin, polymyxin B and norfloxacin. Evaluation of drug interactions was estimated by the checkerboard pattern broth dilution method and by time-kill studies. Rifampin reduced the activity of the three antifungal agents used, with the reduction being more pronounced with amphotericin B. Synergy was observed when polymyxin B was combined with any of the antifungal agents used. The addition of norfloxacin resulted in minimal, if any, change in the activity.

  17. Synthesis and Antifungal Activities of 5-(o-Hydroxy phenyl-2-[4'aryl-3'chloro-2'azetidinon-1-yl]-1,3,4-thiadiazole

    Directory of Open Access Journals (Sweden)

    Shiv K. Gupta

    2011-01-01

    Full Text Available New series of 5-(o-hydroxy phenyl-2-[4'aryl-3'chloro-2'azetidinon-1-yl]-1,3,4-thiadiazole have been synthesized and the structures of the new compounds were established on the basis of IR, 1H NMR spectral data. In vitro antifungal activity (MIC activity was evaluated and compared with standard drugs of ketoconazole. Compounds 3c in the series has shown interesting antifungal activity against both C. albicans and A. niger fungus. In the gratifying result, most of the compounds were found to have moderate antifungal activity.

  18. Nepenthes rafflesiana pitcher liquid has antifungal activity against Candida spp.

    OpenAIRE

    Hanna Yolanda; Ingrid M. Makahinda; Maureen Aprilia; Nikki Sanjaya; Harry Gunawan; Rita Dewi

    2015-01-01

    BACKGROUND To develop new effective antifungals, it is essential to search for antifungal compounds from plants such as Nepenthes spp., which have their greatest diversity in Indonesia. Since chitin-induced liquid (CIL) from Nepenthes khasiana pitchers has antifungal activity, due to their naphthoquinone content, this study aimed to evaluate antifungal activity of Nepenthes rafflesiana pitcher liquids on Candida spp. METHODS Collected pitcher liquids were of 3 types: non-induced l...

  19. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    Energy Technology Data Exchange (ETDEWEB)

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won (Toronto); (IBC-Belarus)

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  20. Antibacterial and antifungal properties of guanylhydrazones

    Directory of Open Access Journals (Sweden)

    Ajdačić Vladimir

    2017-01-01

    Full Text Available A series of novel guanylhydrazones were designed, synthesized and characterized. All the compounds were screened for their antibacterial and antifungal activity. Compounds 26 and 27 showed excellent antibacterial activities against Staphylococcus aureus ATCC 25923 and Micrococcus luteus ATCC 379 with minimal inhibitory concentrations of 4 μg mL-1, and good antifungal activity against Candida parapsilosis ATCC 22019. These results suggested that the selected guanylhydrazones could serve as promising leads for improved antimicrobial development. [Project of the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant No. 172008 and Grant No. 173048

  1. The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and moulds.

    Science.gov (United States)

    Espinel-Ingroff, Ana; Turnidge, John

    2016-01-01

    The role of antimicrobial susceptibility testing is to aid in selecting the best agent for the treatment of bacterial and fungal diseases. This has been best achieved by the setting of breakpoints by Clinical Laboratory Standards Institute (CLSI) for prevalent Candida spp. versus anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) also has set breakpoints for prevalent and common Candida and Aspergillus species versus amphotericin B, itraconazole, and posaconazole. Recently, another interpretive category, the epidemiological cut off value, could aid in the early identification of strains with acquired resistance mechanisms. CLSI has postulated that epidemiological cut off values may, with due caution, aid physicians in managing mycosis by species where breakpoints are not available. This review provides (1) the criteria and statistical approach to establishing and estimating epidemiological cut off values (ECVs), (2) the role of the epidemiological cut off value in establishing breakpoints, (3) the potential role of epidemiological cut off values in clinical practice, (4) and the wide range of CLSI-based epidemiological cut off values reported in the literature as well as EUCAST and Sensititre Yeast One-ECVs. Additionally, we provide MIC/MEC (minimal inhibitory concentrations/minimum effective concentrations) ranges/modes of each pooled distribution used for epidemiological cut off value calculation. We focus on the epidemiological cut off value, the new interpretive endpoint that will identify the non-wild type strains (defined as potentially harboring resistance mechanisms). However, we emphasize that epidemiological cut off values will not categorize a fungal isolate as susceptible or resistant as breakpoints do, because the former do not account for the pharmacology of the antifungal agent or the findings from clinical outcome studies. Copyright © 2016 Asociación Espa

  2. In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF)

    Energy Technology Data Exchange (ETDEWEB)

    Palicz, Zoltán; Jenes, Ágnes; Gáll, Tamás [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Miszti-Blasius, Kornél [Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Kollár, Sándor; Kovács, Ilona [Department of Pathology, Kenézy Hospital LTD, Debrecen (Hungary); Emri, Miklós; Márián, Teréz [Department of Nuclear Medicine, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Leiter, Éva; Pócsi, István [Department of Microbial Biotechnology and Cell Biology, Faculty of Science and Technology, Centre of Arts, Humanities and Sciences, University of Debrecen, Debrecen (Hungary); Csősz, Éva; Kalló, Gergő [Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Hegedűs, Csaba; Virág, László [Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Csernoch, László [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Szentesi, Péter, E-mail: szentesi.peter@med.unideb.hu [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2013-05-15

    The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg{sup −1} daily, for 2 weeks. Even at the highest concentration – a concentration highly toxic in vitro for all affected molds – used, animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. - Highlights: • PAF, the antifungal protein of Penicillium chrysogenum, was not toxic in mice. • Its intranasal application didn't induce pathological reactions in the lung. • PAF retained its antifungal activity in lung extracts. • Its application on the skin did not cause inflammation.

  3. Emerging drugs and vaccines for candidemia.

    Science.gov (United States)

    Moriyama, Brad; Gordon, Lori A; McCarthy, Matthew; Henning, Stacey A; Walsh, Thomas J; Penzak, Scott R

    2014-12-01

    Candidemia and other forms of invasive candidiasis are important causes of morbidity and mortality. The evolving challenge of antimicrobial resistance among fungal pathogens continues to highlight the need for potent, new antifungal agents. MEDLINE, EMBASE, Scopus and Web of Science searches (up to January 2014) of the English-language literature were performed with the keywords 'Candida' or 'Candidemia' or 'Candidiasis' and terms describing investigational drugs with activity against Candida spp. Conference abstracts and the bibliographies of pertinent articles were also reviewed for relevant reports. ClinicalTrials.gov was searched for relevant clinical trials. Currently available antifungal agents for the treatment of candidemia are summarised. Investigational antifungal agents with potential activity against Candida bloodstream infections and other forms of invasive candidiasis and vaccines for prevention of Candida infections are also reviewed as are selected antifungal agents no longer in development. Antifungal agents currently in clinical trials include isavuconazole, albaconazole, SCY-078, VT-1161 and T-2307. Further data are needed to determine the role of these compounds in the treatment of candidemia and other forms of invasive candidiasis. The progressive reduction in antimicrobial drug development may result in a decline in antifungal drug discovery. Still, there remains a critical need for new antifungal agents to treat and prevent invasive candidiasis and other life-threatening mycoses. © 2014 Blackwell Verlag GmbH.

  4. Synthetic multivalent antifungal peptides effective against fungi.

    Directory of Open Access Journals (Sweden)

    Rajamani Lakshminarayanan

    Full Text Available Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010 which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg or intravenous (100 mg/kg routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides.

  5. Prevalence and Antifungal Susceptibility of Candida Species ...

    African Journals Online (AJOL)

    Candidal vulvovaginitis causes extreme discomfort and affects the well being of women. The aim of this study was to determine the prevalence of Candida infections among women attending gynaecological clinic at the Komfo Anokye Teaching Hospital (KATH) in Kumasi and the antifungal susceptibility patterns of the ...

  6. Antifungal diterpenes from Hypoestes serpens (Acanthaceae).

    Science.gov (United States)

    Rasoamiaranjanahary, Lalao; Marston, Andrew; Guilet, David; Schenk, Kurt; Randimbivololona, Fanantenanirainy; Hostettmann, Kurt

    2003-02-01

    Two new diterpenes, fusicoserpenol A and dolabeserpenoic acid A, with antifungal activity, were isolated from leaves of Hypoestes serpens (Acanthaceae). Their structures were elucidated by means of spectrometric methods including 1D and 2D NMR experiments and MS analysis. X-ray crystallographic analysis confirmed the structure of fusicoserpenol A and established the relative configuration.

  7. Species identification and antifungal susceptibility pattern of ...

    African Journals Online (AJOL)

    Dalia Saad ElFeky

    2015-10-23

    Oct 23, 2015 ... Abstract Vulvovaginal candidiasis (VVC) remains one of the most common infections of the female genital tract. Correct identification of the isolated Candida species is essential to direct the empirical antifungal therapy. Objectives: This local study was conducted to identify the spectrum of Candida species ...

  8. Antimycotoxigenic and antifungal activities of Citrullus colocynthis ...

    African Journals Online (AJOL)

    user

    2013-10-23

    Oct 23, 2013 ... 2Laboratory of Technology and Animal Production, University of Abdelhamid Ibn Badis, Mostaganem (27000), Algeria. 3Laboratory of ... results suggest that the extracts showed a very good antifungal activity against A. ochraceus, but for A. ..... activity of essential oil and its constituents from Calocedrus.

  9. Chemical constituents, antibacterial, antifungal and antioxidant ...

    African Journals Online (AJOL)

    ... penicillium notatum and Rhizopus stolonifer) at different concentrations, except ethyl acetate extract which showed no antifungal property on Rhizopus stolonifer. Ethyl acetate and methanol extracts exhibited significant antioxidant activities by scavenging DPPH free radicals with IC of 12.14 and 93.85 μg/ml respectively.

  10. Antifungal potentials of Azardirachta indica and Ocimum ...

    African Journals Online (AJOL)

    Antifungal potentials of Azardirachta indica and Ocimum grattissimum leaf extracts in the control of yam rot. ... Fusarium oxysporium, Botryodiplodia theobromae, Rhizopus stolonifer, Penicilluim notatum and Aspergillus niger were isolated from the rotted yams. Both fresh and dry extracts of the leaves had significant effects ...

  11. Studies on Buddleja asiatica antibacterial, antifungal, antispasmodic ...

    African Journals Online (AJOL)

    Jane

    2011-07-27

    Jul 27, 2011 ... Crude extract of Buddleja asiatica Lour and its fractions, chloroform (F1), ethyl acetate (F2) and n- butanol (F3) were evaluated for antibacterial, antifungal, antispasmodic and Ca++ antagonist activities. The antibacterial activity was performed against 11 types of bacteria. The crude extract and fractions F2.

  12. Species identification and antifungal susceptibility pattern of ...

    African Journals Online (AJOL)

    Species identification of Candida isolates was done using phenotypic methods including germ tube test, Rice Tween-80 agar, Chrom ID (CAN2) agar and API 20C AUX, while PCR-RFLP was used as the gold standard method. Antifungal susceptibility testing was done using the disk diffusion method. Results: Vaginal swab ...

  13. Antifungal evaluation and phytochemical screening of methanolic ...

    African Journals Online (AJOL)

    The objective of the study was to further examine the medicinal value of Boswellia dalzielii plant by evaluating the antifungal activity and carrying out phytochemical screening of methanolic extract, hexane, ethyl acetate, aqueous fractions and the sub-fractions of the stem bark of the plant. Standard methods were used for ...

  14. Exploiting mitochondria as targets for the development of new antifungals.

    Science.gov (United States)

    Li, Dongmei; Calderone, Richard

    2017-02-17

    Mitochondria are essential for cell growth and survival of most fungal pathogens. Energy (ATP) produced during oxidation/reduction reactions of the electron transport chain (ETC) Complexes I, III and IV (CI, CIII, CIV) fuel cell synthesis. The mitochondria of fungal pathogens are understudied even though more recent published data suggest critical functional assignments to fungal-specific proteins. Proteins of mammalian mitochondria are grouped into 16 functional categories. In this review, we focus upon 11 proteins from 5 of these categories in fungal pathogens, OXPHOS, protein import, stress response, carbon source metabolism, and fission/fusion morphology. As these proteins also are fungal-specific, we hypothesize that they may be exploited as targets in antifungal drug discovery. We also discuss published transcriptional profiling data of mitochondrial CI subunit protein mutants, in which we advance a novel concept those CI subunit proteins have both shared as well as specific responsibilities for providing ATP to cell processes.

  15. Antifungal Activity of Commercial Essential Oils and Biocides against Candida Albicans.

    Science.gov (United States)

    Serra, Elisa; Hidalgo-Bastida, Lilia Araida; Verran, Joanna; Williams, David; Malic, Sladjana

    2018-01-25

    Management of oral candidosis, most frequently caused by Candida albicans , is limited due to the relatively low number of antifungal drugs and the emergence of antifungal tolerance. In this study, the antifungal activity of a range of commercial essential oils, two terpenes, chlorhexidine and triclosan was evaluated against C. albicans in planktonic and biofilm form. In addition, cytotoxicity of the most promising compounds was assessed using murine fibroblasts and expressed as half maximal inhibitory concentrations (IC50). Antifungal activity was determined using a broth microdilution assay. The minimum inhibitory concentration (MIC) was established against planktonic cells cultured in a range of concentrations of the test agents. The minimal biofilm eradication concentration (MBEC) was determined by measuring re-growth of cells after pre-formed biofilm was treated for 24 h with the test agents. All tested commercial essential oils demonstrated anticandidal activity (MICs from 0.06% ( v / v ) to 0.4% ( v / v )) against planktonic cultures, with a noticeable increase in resistance exhibited by biofilms (MBECs > 1.5% ( v / v )). The IC50s of the commercial essential oils were lower than the MICs, while a one hour application of chlorhexidine was not cytotoxic at concentrations lower than the MIC. In conclusion, the tested commercial essential oils exhibit potential as therapeutic agents against C. albicans , although host cell cytotoxicity is a consideration when developing these new treatments.

  16. In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.

    Science.gov (United States)

    Zuo, Ran; Garrison, Aaron T; Basak, Akash; Zhang, Peilan; Huigens, Robert W; Ding, Yousong

    2016-08-01

    With the increasing prevalence of fungal infections coupled with emerging drug resistance, there is an urgent need for new and effective antifungal agents. Here we report the antifungal activities of 19 diverse halogenated quinoline (HQ) small molecules against Candida albicans and Cryptococcus neoformans. Four HQ analogues inhibited C. albicans growth with a minimum inhibitory concentration (MIC) of 100 nM, whilst 16 analogues effectively inhibited C. neoformans at MICs of 50-780 nM. Remarkably, two HQ analogues eradicated mature C. albicans and C. neoformans biofilms [minimum biofilm eradication concentration (MBEC) = 6.25-62.5 µM]. Several active HQs were found to penetrate into fungal cells, whilst one inactive analogue was unable to, suggesting that HQs elicit their antifungal activities through an intracellular mode of action. HQs are a promising class of small molecules that may be useful in future antifungal treatments. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  17. Antifungal Activity of Commercial Essential Oils and Biocides against Candida Albicans

    Directory of Open Access Journals (Sweden)

    Elisa Serra

    2018-01-01

    Full Text Available Management of oral candidosis, most frequently caused by Candida albicans, is limited due to the relatively low number of antifungal drugs and the emergence of antifungal tolerance. In this study, the antifungal activity of a range of commercial essential oils, two terpenes, chlorhexidine and triclosan was evaluated against C. albicans in planktonic and biofilm form. In addition, cytotoxicity of the most promising compounds was assessed using murine fibroblasts and expressed as half maximal inhibitory concentrations (IC50. Antifungal activity was determined using a broth microdilution assay. The minimum inhibitory concentration (MIC was established against planktonic cells cultured in a range of concentrations of the test agents. The minimal biofilm eradication concentration (MBEC was determined by measuring re-growth of cells after pre-formed biofilm was treated for 24 h with the test agents. All tested commercial essential oils demonstrated anticandidal activity (MICs from 0.06% (v/v to 0.4% (v/v against planktonic cultures, with a noticeable increase in resistance exhibited by biofilms (MBECs > 1.5% (v/v. The IC50s of the commercial essential oils were lower than the MICs, while a one hour application of chlorhexidine was not cytotoxic at concentrations lower than the MIC. In conclusion, the tested commercial essential oils exhibit potential as therapeutic agents against C. albicans, although host cell cytotoxicity is a consideration when developing these new treatments.

  18. The Sesamum indicum rhizosphere associated bacterium: A source of Antifungal compound.

    Science.gov (United States)

    Chaudhary, Renu; Balhara, Meenakshi; Jangir, Deepak; Dangi, Mrridula; Dangi, Mehak; Khatri, Savita; Chhillar, Anil K

    2018-02-05

    The impact of fungal infections on human health has increased considerably within a past few decades. Although drugs with antifungal properties are available, but they are less effective and are associated with side effects. Screening of bacterial isolates from Sesamum indicum and to investigate the antifungal activity of the screened bacterial isolates against Aspergillus sp. Co-culture assay and agar overlay were used to scrutinize the anti-Aspergillus activity. Furthermore, optimization ofmedia and growth conditions to enhance the production of anti-Aspergillus compound. Several bacterial cultures were isolated from Sesamum indicum rhizosphere collected from Mandi (H.P.) India. These bacterial cultures were assayed for antifungal activity against Aspergillus species i.e. A. fumigatus and A. niger. Two most potent strains were chosen for more detailed analyses. The biochemical characterization and 16S ribosomal RNA sequencing revealed that Burkholderia sp. strain RC1 and Acinetobacter pittii strain RC2 exhibits strong similarity (100%) with Burkholderia sp. SR2-07 and Acinetobacter sp. strain 3-59. Additionally, it was also validated that RC1 and RC2 showed significant difference in the production of anti-Aspergillusactivity under altered growth conditions. Results from this study recommends that plant rhizosphere remains a rich hotspot for delivering a novel antifungal compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. In vitro antifungal susceptibility and molecular identity of 99 clinical isolates of the opportunistic fungal genus Curvularia

    NARCIS (Netherlands)

    Cunha, da K.C.; Sutton, D.A.; Fothergill, A.W.; Gené, J.; Cano, J.; Madrid, H.; Hoog, de G.S.; Crous, P.W.; Guarro, J.

    2013-01-01

    The in vitro antifungal susceptibility of a set of 99 clinical isolates of Curvularia was tested against 9 drugs using a reference microdilution method. The isolates had been identified previously to species level by comparing their ITS rDNA and glyceraldehyde-3-phosphate dehydrogenase gene

  20. The novel antifungal agent PLD-118 is neither metabolized by liver microsomes nor inhibits cytochrome P450 in vitro

    NARCIS (Netherlands)

    Parnham, M.J.; Bogaards, J.J.P.; Schrander, F.; Schut, M.W.; Orešković, K.; Mildner, B.

    2005-01-01

    PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with

  1. Sensitivity of Candida albicans to essential oils: are they an alternative to antifungal agents?

    Science.gov (United States)

    Bona, E; Cantamessa, S; Pavan, M; Novello, G; Massa, N; Rocchetti, A; Berta, G; Gamalero, E

    2016-12-01

    Candida albicans is an important opportunistic pathogen, responsible for the majority of yeast infections in humans. Essential oils, extracted from aromatic plants, are well-known antimicrobial agents, characterized by a broad spectrum of activities, including antifungal properties. The aim of this work was to assess the sensitivity of 30 different vaginal isolated strains of C. albicans to 12 essential oils, compared to the three main used drugs (clotrimazole, fluconazole and itraconazole). Thirty strains of C. albicans were isolated from vaginal swab on CHROMagar ™ Candida. The agar disc diffusion method was employed to determine the sensitivity to the essential oils. The antifungal activity of the essential oils and antifungal drugs (clotrimazole, itraconazole and fluconazole) were investigated using a microdilution method. Transmission and scanning electron microscopy analyses were performed to get a deep inside on cellular damages. Mint, basil, lavender, tea tree oil, winter savory and oregano essential oils inhibited both the growth and the activity of C. albicans more efficiently than clotrimazole. Damages induced by essential oils at the cellular level were stronger than those caused by clotrimazole. Candida albicans is more sensitive to different essential oils compared to the main used drugs. Moreover, the essential oil affected mainly the cell wall and the membranes of the yeast. The results of this work support the research for new alternatives or complementary therapies against vaginal candidiasis. © 2016 The Society for Applied Microbiology.

  2. DFT vibrational assignments, in vitro antifungal activity, genotoxic and acute toxicity determinations of the [Zn(phen)2(cnge)(H2O)](NO3)2·H2O complex

    Science.gov (United States)

    Martínez Medina, Juan J.; Torres, Carola A.; Alegre, Walter S.; Franca, Carlos A.; López Tévez, Libertad L.; Ferrer, Evelina G.; Okulik, Nora B.; Williams, Patricia A. M.

    2015-11-01

    Calculations based on density functional methods were carried out for the [Zn(phen)2(cnge)(H2O)](NO3)2·H2O complex taking into account the presence of two different conformers for the cyanoguanidine ligand. The calculated geometrical parameters and the vibrational IR and Raman spectra were in agreement with the experimental data. On the other hand, the activities of the complex, the ligands and the metal against fungal strains have been measured. The complexation increased the antifungal activity of the metal and the ligand cyanoguanidine, and slightly decreased the antifungal activity of the ligand 1,10-phenanthroline against Candida albicans, C. albicans ATCC 10231 and Candida krusei (not against the others strains of Candida). The ligand 1,10-phenanthroline and the zinc complex showed in some cases higher activity than the common antifungal drug fluconazole. The complexation also increased the post-antifungal effect in the tested strains, except for Candida parapsilosis, even with a better efficiency than those of some conventional antifungal agents. Antifungal studies were coupled with safety evaluations using the Artemia salina and the Ames tests. The zinc complex behaved as a non-mutagenic and non-toxic compound at the tested concentrations. Moreover, the zinc complex could be safer than the ligand when used as an antifungal agent. Therefore, the interaction of zinc(II) with N-containing ligands may provide a promising strategy for the development of novel and more secure drugs with antifungal activity.

  3. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

    Science.gov (United States)

    Fung, Monica; Kim, Jane; Marty, Francisco M; Schwarzinger, Michaël; Koo, Sophia

    2015-01-01

    Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We

  4. Liquid and vapour-phase antifungal activities of essential oils against Candida albicans and non-albicans Candida.

    Science.gov (United States)

    Mandras, Narcisa; Nostro, Antonia; Roana, Janira; Scalas, Daniela; Banche, Giuliana; Ghisetti, Valeria; Del Re, Simonetta; Fucale, Giacomo; Cuffini, Anna Maria; Tullio, Vivian

    2016-08-30

    The management of Candida infections faces many problems, such as a limited number of antifungal drugs, toxicity, resistance of Candida to commonly antifungal drugs, relapse of Candida infections, and the high cost of antifungal drugs. Though azole antifungal agents and derivatives continue to dominate as drugs of choice against Candida infections, there are many available data referring to the anticandidal activity of essential oils. Since we have previous observed a good antimicrobial activity of some essential oils against filamentous fungi, the aim of this study was to extend the research to evaluate the activity of the same oils on Candida albicans, C.glabrata and C.tropicalis clinical strains, as well as the effects of related components. Essential oils selection was based both on ethnomedicinal use and on proved antibacterial and/or antifungal activity of some of these oils. Fluconazole and voriconazole were used as reference drugs. The minimum inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) of essential oils (thyme red, fennel, clove, pine, sage, lemon balm, and lavender) and their major components were investigated by the broth microdilution method (BM) and the vapour contact assay (VC). Using BM, pine oil showed the best activity against all strains tested, though C.albicans was more susceptible than C.glabrata and C.tropicalis (MIC50-MIC90 = 0.06 %, v/v). On the contrary, sage oil displayed a weak activity (MIC50-MIC90 = 1 %, v/v). Thyme red oil (MIC50-MIC90 ≤ 0.0038 %, v/v for C.albicans and C.tropicalis, and 0.0078- Candida spp., including fluconazole/voriconazole resistant strains. These data encourage adequately controlled and randomized clinical investigations. The use in vapour phase could have additional advantages without requiring direct contact, resulting in easy of environmental application such as in hospital, and/or in school.

  5. In vitro antifungal susceptibility of clinical species belonging to Aspergillus genus and Rhizopus oryzae.

    Science.gov (United States)

    Kachuei, R; Khodavaisy, S; Rezaie, S; Sharifynia, S

    2016-03-01

    Among filamentous fungal pathogens, Aspergillus spp. and zygomycetes account for highest rates of morbidity and mortality among immunocompromised patients. Recently developed antifungal drugs offer the potential to improve management and therapeutic outcomes of fungal infections. The aim of this study was to analyse the in vitro activities of voriconazole, itraconazole, amphotericin B and caspofungin against clinical isolates of Aspergillus spp. and Rhizopus oryzae. The in vitro antifungal susceptibility of 54 isolates belonging to different clinical isolates of Aspergillus spp. and R. oryzae was tested for four antifungal agents using a microdilution reference method (CLSI, M38-A2). All isolates were identified by typical colony and microscopic characteristics, and also characterized by molecular methods. Caspofungin (MEC range: 0.008-0.25 and MEC50: 0.0023μg/mL) was the most active drug in vitro against Aspergillus spp., followed by voriconazole (MIC range: 0.031-8 and MIC50: 0.5μg/mL), itraconazole (MIC range: 0.031-16 and MIC50: 0.25μg/mL), and amphotericin B (MIC range: 0.125-4 and MIC50: 0.5μg/mL), in order of decreasing activity. The caspofungin, voriconazole, and itraconazole demonstrated poor in vitro activity against R. oryzae isolates evaluated, followed by amphotericin B. This study demonstrates that caspofungin had good antifungal activity and azole agents had better activity than amphotericin B against Aspergillus species. Although, azole drugs are considered ineffective against R. oryzae. This result is just from a small scale in vitro susceptibility study and we did not take other factors into consideration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Chemical composition and antifungal activity of Carica papaya Linn. seed essential oil against Candida spp.

    Science.gov (United States)

    He, X; Ma, Y; Yi, G; Wu, J; Zhou, L; Guo, H

    2017-05-01

    In recent years, the incidence of clinical yeast infections has increased dramatically. Due to the extensive use of broad-spectrum antifungal agents, there has been a notable increase in drug resistance among infections yeast species. As one of the most popular natural antimicrobial agents, essential oils (EOs) have attracted a lot of attention from the scientific community. The aim of this study was to analyse the chemical composition and examine the antifungal activity of the EO extracted from the seeds of Carica papaya Linn. The papaya seed EO was analysed by gas chromatography-mass spectrometry. The major constituent is benzyl isothiocyanate (99·36%). The filter paper disc diffusion method and broth dilution method were employed. The EO showed inhibitory effect against all the tested Candida strains including C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropical with inhibition zone diameters in the range of 14·2-33·2 mm, the minimal inhibitory concentrations (MICs) in the range of 4·0-16·0 μg ml -1 and the minimum fungicidal concentrations (MFCs) in the range of 16·0-64·0 μg ml -1 . Here, we found that the papaya seed EO has promising anticandida activity and identify C. papaya L. as a potential natural source of antifungal agents. The chemical composition and antifungal activity of essential oil of Carica papaya seeds were studied. The oil of papaya seeds could inhibit the growth of Candida spp. for the first report. Carica Papaya may be recognized as a possible new source of natural antifungal agents. © 2017 The Society for Applied Microbiology.

  7. Anti-inflammatory activity of Vismia guianensis (Aubl.) Pers. extracts and antifungal activity against Sporothrix schenckii.

    Science.gov (United States)

    Oliveira, A H; de Oliveira, G G; Carnevale Neto, F; Portuondo, D F; Batista-Duharte, A; Carlos, I Z

    2017-01-04

    Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Antifungal susceptibility testing of Candida in the Clinical Laboratory: how to do it, when to do it, and how to interpret it

    Directory of Open Access Journals (Sweden)

    Esther Manso

    2014-06-01

    Full Text Available Significant changes in the management of fungaemia have occurred in the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. The emergence of drug resistance in fungal pathogens has a profound impact on human health given limited number of antifungal drugs. Antifungal resistance in Candida may be either intrinsic or acquired and may be encountered in the antifungal drug exposed but also the antifungal drug naïve patient The variation in resistance rates between centers emphasizes that it is essential to have knowledge of the local Candida species distribution and antifungal resistance rates to guide initial therapy for Candida BSI. Moreover, all Candida isolates from blood and normally sterile sites should be identified to the species level. The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing have developed breakpoints and epidemiological cutoff values that are now established for Candida spp. Clinical microbiology laboratories will be employed commercial susceptibility assays, rather than reference broth microdilution methods and comparative studies are particularly important. Vitek 2®, Etest® and Sensititre YeastOne® provided a high degree of essential agreement and comparable sensitivity and specificity to BMD-RPMI for identifying resistance to azole and echinocandins in Candida spp.

  9. Antifungal activity of 10 Guadeloupean plants.

    Science.gov (United States)

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Antifungal Activity of Homoaconitate and Homoisocitrate Analogs

    Directory of Open Access Journals (Sweden)

    Sławomir Milewski

    2012-11-01

    Full Text Available Thirteen structural analogs of two initial intermediates of the L-a-aminoadipate pathway of L-lysine biosynthesis in fungi have been designed and synthesized, including fluoro- and epoxy-derivatives of homoaconitate and homoisocitrate. Some of the obtained compounds exhibited at milimolar range moderate enzyme inhibitory properties against homoaconitase and/or homoisocitrate dehydrogenase of Candida albicans. The structural basis for homoisocitrate dehydrogenase inhibition was revealed by molecular modeling of the enzyme-inhibitor complex. On the other hand, the trimethyl ester forms of some of the novel compounds exhibited antifungal effects. The highest antifungal activity was found for trimethyl trans-homoaconitate, which inhibited growth of some human pathogenic yeasts with minimal inhibitory concentration (MIC values of 16–32 mg/mL.

  11. Antibacterial and Antifungal Activities of Spices.

    Science.gov (United States)

    Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin

    2017-06-16

    Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices-such as clove, oregano, thyme, cinnamon, and cumin-possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens , pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.

  12. Combination Antifungal Therapy for Cryptococcal Meningitis

    OpenAIRE

    Day, Jeremy N.; Chau, Tran T.H.; Wolbers, Marcel; Mai, Pham P.; Dung, Nguyen T.; Mai, Nguyen H.; Phu, Nguyen H.; Nghia, Ho D.; Phong, Nguyen D.; Thai, Cao Q.; Thai, Le H.; Chuong, Ly V.; Sinh, Dinh X.; Duong, Van A.; Hoang, Thu N.

    2013-01-01

    Background\\ud Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.\\ud Methods\\ud We conducted a randomized, three-group, open-label trial of induction the...

  13. Antifungal Efficacy of Myrtus communis Linn

    OpenAIRE

    Sadeghi Nejad; Erfani Nejad; Yusef Naanaie; Zarrin

    2014-01-01

    Background The ethanolic extract of Myrtus communis Linn. leaves was assayed in vitro as a growth inhibitor against opportunistic fungi such as Candida and Aspergillus species. Myrtus communis Linn. (Family, Myrtaceae) is an aromatic evergreen shrub or small tree. It is native to the Mediterranean region. Objectives This study aimed to assess antifungal activity (in vitro) of the ethanolic extracts of Myrtus communis leaves as a g...

  14. Antifungal susceptibility testing of Aspergillus species complex in the Clinical Laboratory: how to do it, when to do it, and how to interpret it

    Directory of Open Access Journals (Sweden)

    Esther Manso

    2014-12-01

    Full Text Available The emergence of drug resistance in fungal pathogens has a profound impact on human health given limited number of antifungal drugs. Antifungal resistance in Aspergillus spp. infection can be encountered in the antifungal drug-exposed patient due to selection of intrinsically resistant species or isolates with acquired resistance belonging to species that are normally susceptible. Resistance to triazoles is not common in Aspergillus spp., however, triazole resistance in A. fumigatus appears to be increasing in several European countries in recent years and can be clinically relevant. The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing have developed breakpoints and epidemiological cutoff values that are now established for Aspergillus spp. Clinical microbiology laboratories will be employed commercial susceptibility assays, rather than reference broth microdilution methods and comparative studies are particularly important.

  15. Antifungal Activity of Maytenin and Pristimerin

    Science.gov (United States)

    Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

    2012-01-01

    Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

  16. Antifungal Activity of Maytenin and Pristimerin

    Directory of Open Access Journals (Sweden)

    Fernanda P. Gullo

    2012-01-01

    Full Text Available Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa. It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents.

  17. Antifungal Efficacy of Myrtus communis Linn

    Directory of Open Access Journals (Sweden)

    Sadeghi Nejad

    2014-08-01

    Full Text Available Background The ethanolic extract of Myrtus communis Linn. leaves was assayed in vitro as a growth inhibitor against opportunistic fungi such as Candida and Aspergillus species. Myrtus communis Linn. (Family, Myrtaceae is an aromatic evergreen shrub or small tree. It is native to the Mediterranean region. Objectives This study aimed to assess antifungal activity (in vitro of the ethanolic extracts of Myrtus communis leaves as a growth inhibitor against 24 clinical isolates of Candida, including C. albicans, C. glabrata, and C. tropicalis also three species of Aspergillus, including A. niger, A. flavus, and A. terreus. Materials and Methods The ethanolic extract of myrtle leaves was prepared by maceration method and minimal inhibitory concentration (MIC of Myrtus communis leaves extract was determined by agar-well diffusion technique. Amphotericin B and clotrimazole were used as the positive control in this assay. Results The minimal inhibitory concentration (MICs values of Myrtus communis leaves extract ranged 0.625-5.0 µg/µL and 5-40 µg/µL against tested Candida spp. and Aspergillus spp., respectively. Conclusions Results revealed that the ethanolic extract of Myrtus communis leaves have antifungal potency against both pathogenic tested fungi, and it can be used as a natural antifungal agent.

  18. Antifungal immunity in selected fungal infections

    Directory of Open Access Journals (Sweden)

    Alicja Trzeciak-Ryczek

    2015-04-01

    Full Text Available Fungi are omnipresent in the environment; hence they are frequent factors causing infections in humans and animals even if their immune system works correctly. These facts stimulated interest in and the will to understand the antifungal immunity mechanisms. It has been, however, evidenced that the immunological response to mycotic pathogens is related to the species and morphological form of the fungus. Nevertheless, it is assumed that always in the antifungal response, there are mechanisms of innate and adaptive immunity that cooperate with one another to eliminate such pathogens. It has been evidenced that the main elements of antifungal immunity are physical barriers of the organism, phagocytosis, cytotoxicity, and possibly trogocytosis of PMN and MN cells, as well as T-cells, and to a smaller extent B-cells, the proportion of which is principally related to their products activating the processes of PMN and MN cells. An important role in this immunity also belongs to PRR, which activate the main processes of phagocytosis and cytotoxicity of PMN, MN, NK and DC cells.

  19. Inhibition of Propionibacterium acnes lipase activity by the antifungal agent ketoconazole.

    Science.gov (United States)

    Unno, Mizuki; Cho, Otomi; Sugita, Takashi

    2017-01-01

    The common skin disease acne vulgaris is caused by Propionibacterium acnes. A lipase secreted by this microorganism metabolizes sebum and the resulting metabolites evoke inflammation in human skin. The antifungal drug ketoconazole inhibits P. acnes lipase activity. We previously showed that the drug also inhibits the growth of P. acnes. Thus, ketoconazole may serve as an alternative treatment for acne vulgaris, which is important because the number of antibiotic-resistant P. acnes strains has been increasing. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  20. Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

    Science.gov (United States)

    Wazir, Asma; Mehjabeen, -; Jahan, Noor; Sherwani, Sikander Khan; Ahmad, Mansoor

    2014-11-01

    The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200μg/ml was 70% DPPH scavenging activity (EC50=937.5μg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100μg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments.

  1. Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum.

    Science.gov (United States)

    Sadiq, Abdul; Ahmad, Sadiq; Ali, Rahmat; Ahmad, Fawad; Ahmad, Sajjad; Zeb, Anwar; Ayaz, Muhammad; Ullah, Farhat; Siddique, Abu Nasar

    2016-11-24

    Herbal medicines have long been used for various ailments in various societies and natural bioactive compounds are gaining more and more importance due to various factors. In this context, three plant species i.e., Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum have been aimed for the scientific verification of their purported traditional uses against various infectious diseases. In this study, three plants were assayed for antibacterial and antifungal potentials. The antibacterial investigations were performed via well diffusion method and nutrient broth dilution method. The bacterial strains used in the study were Enterococcus faecalis, Proteus mirabilis, Escherichia coli, Salmonella typhi, Klebsiella pneumonia and Pseudomonas aeruginosa. The antifungal potential was investigated by dilution method of Muller-Hinton agar media of the plants' samples. The fungal strains used were Aspergillis fumigatus, Aspergillis flavus and Aspergillis niger. Ceftriaxone and nystatin were used as standard drugs in antibacterial and antifungal assays respectively. Different fractions from N. thomsonianum were tested against five bacterial strains while the samples from A. consanguineum and E. caeruleum were tested against six bacterial strains. All the samples exhibited prominent antibacterial activity against the tested strains. Overall, chloroform and ethyl acetate fractions were found most potent among the three plants' samples. N. thomsonianum excelled among the three plants in antibacterial activity. Similarly, in antifungal assay, N. thomsonianum exhibited strong antifungal activity against the fungal strains. The chloroform fraction displayed MFCs of 175.67 ± 5.20***, 29.33 ± 5.48*** and 63.00 ± 4.93*** μg/ml against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger respectively. The whole study demonstrates that all the three plant species were active against tested bacterial and fungal strains. It can be concluded from

  2. Catalytic Synthesis and Antifungal Activity of New Polychlorinated Natural Terpenes

    Directory of Open Access Journals (Sweden)

    Hana Ighachane

    2017-01-01

    Full Text Available Various unsaturated natural terpenes were selectively converted to the corresponding polychlorinated products in good yields using iron acetylacetonate in combination with nucleophilic cocatalyst. The synthesized compounds were evaluated for their in vitro antifungal activity. The antifungal bioassays showed that 2c and 2d possessed significant antifungal activity against Fusarium oxysporum f. sp. albedinis (Foa, Fusarium oxysporum f. sp. canariensis (Foc, and Verticillium dahliae (Vd.

  3. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

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    Partha Pratim Das

    2016-01-01

    Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%, C. dubliniensis (n=9, 14.7%, C. parapsilosis (n=2, 3.2%, C. glabrata (n=2, 3.2%, and C. famata (n=1, 1.6%. Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control group. Antifungal susceptibility testing revealed (n=6, 9.3% C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

  4. Antifungal susceptibilities and identification of species of the Sporothrix schenckii complex isolated in Brazil.

    Science.gov (United States)

    Ottonelli Stopiglia, Cheila Denise; Magagnin, Cibele Massotti; Castrillón, Mauricio Ramírez; Mendes, Sandra Denise Camargo; Heidrich, Daiane; Valente, Patricia; Scroferneker, Maria Lúcia

    2014-01-01

    Sporotrichosis is a subacute or chronic mycosis caused worldwide by the dimorphic species complex, Sporothrix schenckii. We studied 85 isolates recovered in Brazil to verify their identification and evaluate their in vitro antifungal susceptibility patterns. Based on phenotypic tests (microscopic features, ability to grow at 30°C and 37°C, colony diameters, as well as assimilation of sucrose and raffinose) and molecular assays (amplification of a fragment of the calmodulin gene), the strains were identified as S. schenckii, S. brasiliensis and S. globosa, with a predominance of S. schenckii isolates. There was 37.7% disagreement between the phenotypic and genotypic identification methodologies. In general, terbinafine was the most active drug, followed by ketoconazole and itraconazole, and the less active fluconazole and voriconazole. Five isolates (one S. globosa and four S. schenckii) were found to be itraconazole-resistant strains but, in general, there were no differences in the in vitro antifungal susceptibility profiles among the Sporothrix species.

  5. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2014-01-01

    used Saccharomyces cerevisiae as a model for drug susceptibility of yeast biofilms. Confocal laser scanning microscopy showed that S. cerevisiae and C. glabrata form similarly structured biofilms and that the viable cell numbers were significantly reduced by treatment of mature biofilms...... with amphotericin B but not voriconazole, flucytosine, or caspofungin. We showed that metabolic activity in yeast biofilm cells decreased with time, as visualized by FUN-1 staining, and mature, 48-hour biofilms contained cells with slow metabolism and limited growth. Time-kill studies showed that in exponentially...... growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response...

  6. Lamisil, a potent alternative antifungal drug for otomycosis

    Directory of Open Access Journals (Sweden)

    Ali Zarei Mahmoudabadi

    2015-01-01

    Results: Out of 23 isolates of Aspergillus, Candida 4(17.4% and 1(4.4% were resistant to nystatin and miconazole, respectively. In addition, all tested organisms were sensitive to clotrimazole and terbinafine. Statistical analysis has shown that there are no significant differences on the effects of clotrimazole, miconazole and, terbinafine on saprophytic (environmental and pathogenic isolates of A. niger, A. flavus, and A. terreus (P value= 0.85. In addition, all tested organisms were found to be highly susceptible to terbinafine (P< 0.04. Conclusion: This is a new approach for the possible use of Lamisil for the treatment of otomycosis.

  7. Antifungal drug susceptibility of Candida albicans | Bii | East African ...

    African Journals Online (AJOL)

    East African Medical Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 79, No 3 (2002) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Download this PDF file. The PDF file you selected should ...

  8. Antifungal activity and molecular identification of endophytic fungi ...

    African Journals Online (AJOL)

    Antifungal activity and molecular identification of endophytic fungi from the angiosperm Rhodomyrtus tomentosa. Juthatip Jeenkeawpieam, Souwalak Phongpaichit, Vatcharin Rukachaisirikul, Jariya Sakayaroj ...

  9. Candida and candidiasis: the cell wall as a potential molecular target for antifungal therapy.

    Science.gov (United States)

    Gozalbo, Daniel; Roig, Patricia; Villamón, Eva; Gil, María Luisa

    2004-06-01

    The fungal species Candida albicans is an opportunistic pathogen, which causes serious infections in humans, particularly in immunocompromised patients. Depending on the underlying host defect, C. albicans causes a variety of infections, ranging from superficial mucocutaneous candidiasis to life-threatening disseminated infections. Both the limited spectrum of antifungal drugs currently in clinical use and the emergence of resistances make necessary the development of new effective antifungal drugs with minimal side effects; however, such a research is limited by the small number of specific target sites identified to date. The cell wall is a fungal specific dynamic structure essential to almost every aspect of the biology and pathogenicity of C. albicans. Its structure confers physical protection and shape to fungal cells, and as the most external part of the fungus, the cell wall mediates the interaction with the host, including adhesion to host tissues and modulation of the host anti-Candida immune response. Consequently, the fungal cell wall can be considered as a suitable target for development of new antifungal compounds. Therefore two distinct types of potential cell wall-related targets can be envisaged, according to their mode of action in inhibiting infection: (i) inhibition of cell wall biogenesis, which may impair cell wall integrity and thus cell viability, and (ii) modification of host-fungus interactions by inhibiting or blocking putative virulence factors, which may impair host colonization and progress of the infectious process. Antibodies specific to cell wall antigens may protect against infection by a variety of mechanisms and may evolve into save antifungal agents.

  10. 78 FR 35155 - Establishing a List of Qualifying Pathogens Under the Food and Drug Administration Safety and...

    Science.gov (United States)

    2013-06-12

    ... lethal to patients with chronic compensated diseases such as cirrhosis or diabetes mellitus or may hasten...). GAIN is intended to encourage development of new antibacterial and antifungal drugs for the treatment... encourage development of new antibacterial and antifungal drugs for the treatment of serious or life...

  11. In Vitro Antibacterial and Antifungal Activity and Datura Innoxia Extracts

    Directory of Open Access Journals (Sweden)

    Adam IY Shama

    2014-09-01

    Full Text Available The aim of this study was evaluated the Antimicrobial Activity of extraction of Datura innoxia (Seeds, leaves and roots. Datura innoxia Seeds, leaves and roots were collected to examine their antimicrobial activity. Extracts of different parts of the plant were tested against standard microorganisms by using the agar- well diffusion method. Extracts of methanol, and aqueous of seeds, leaves and roots were prepared and tested against four types of bacteria namely: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris and two types of fungi namely: Aspergillus niger and Candida albicans. The methanolic and aqueous extracts of leaves showed high activities against fungi (A. niger and less effect on the all bacteria. The methanolic extracts of seeds showed high activities against all organisms except fungi (C. albicanas, while the aqueous extracts of seeds showed no activity on the bacteria. All organisms were examined against known standard antibiotics and then compare the results of plant extracts with standard antibiotics. The results indicated that the antibacterial drug is less active than the plant extracts, while the antifungal drugs are more active than the plant extracts. DOI: http://dx.doi.org/10.3126/ije.v3i3.11077 International Journal of Environment Vol.3(3 2014: 173-185

  12. The Hsp90 co-chaperones Sti1, Aha1, and P23 regulate adaptive responses to antifungal azoles

    Directory of Open Access Journals (Sweden)

    Xiaokui Gu

    2016-10-01

    Full Text Available Heat Shock Protein 90 (Hsp90 is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of Neurospora crassa mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast, Aha1, and P23 (Sba1 in yeast were required for the basal resistance to antifungal azoles and heat stress. Deletion of any of them resulted in hypersensitivity to azoles and heat. Liquid chromatography–mass spectrometry (LC-MS analysis showed that the toxic sterols eburicol and 14α-methyl-3,6-diol were significantly accumulated in the sti1 and p23 deletion mutants after ketoconazole treatment, which has been shown before to led to cell membrane stress. At the transcriptional level, Aha1, Sti1, and P23 positively regulate responses to ketoconazole stress by erg11 and erg6, key genes in the ergosterol biosynthetic pathway. Aha1, Sti1, and P23 are highly conserved in fungi, and sti1 and p23 deletion also increased the susceptibility to azoles in Fusarium verticillioides. These results indicate that Hsp90-cochaperones Aha1, Sti1, and P23 are critical for the basal azole resistance and could be potential targets for developing new antifungal agents.

  13. Clinicomycological Profile and Antifungal Sensitivity Pattern of Commonly Used Azoles in Dermatophytosis

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    Mahesh Mathur

    2015-06-01

    Conclusions: This study highlighted the increasing resistance of the antifungals, which is responsible for the treatment failure in dermatophye infections. Keywords: antifungal resistance; dermatophyte; epidemiology.

  14. Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links

    Directory of Open Access Journals (Sweden)

    Standaert Annie

    2006-05-01

    Full Text Available Abstract Background Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. Methods During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs Results Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995–2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995–2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615629 € a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995–2000. Conclusion Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with

  15. A new method to predict the epidemiology of fungal keratitis by monitoring the sales distribution of antifungal eye drops in Brazil.

    Directory of Open Access Journals (Sweden)

    Marlon Moraes Ibrahim

    Full Text Available PURPOSE: Fungi are a major cause of keratitis, although few medications are licensed for their treatment. The aim of this study is to observe the variation in commercialisation of antifungal eye drops, and to predict the seasonal distribution of fungal keratitis in Brazil. METHODS: Data from a retrospective study of antifungal eye drops sales from the only pharmaceutical ophthalmologic laboratory, authorized to dispense them in Brazil (Opthalmos were gathered. These data were correlated with geographic and seasonal distribution of fungal keratitis in Brazil between July 2002 and June 2008. RESULTS: A total of 26,087 antifungal eye drop units were sold, with a mean of 2.3 per patient. There was significant variation in antifungal sales during the year (p<0.01. A linear regression model displayed a significant association between reduced relative humidity and antifungal drug sales (R2 = 0.17,p<0.01. CONCLUSIONS: Antifungal eye drops sales suggest that there is a seasonal distribution of fungal keratitis. A possible interpretation is that the third quarter of the year (a period when the climate is drier, when agricultural activity is more intense in Brazil, suggests a correlation with a higher incidence of fungal keratitis. A similar model could be applied to other diseases, that are managed with unique, or few, and monitorable medications to predict epidemiological aspects.

  16. A new method to predict the epidemiology of fungal keratitis by monitoring the sales distribution of antifungal eye drops in Brazil.

    Science.gov (United States)

    Ibrahim, Marlon Moraes; de Angelis, Rafael; Lima, Acacio Souza; Viana de Carvalho, Glauco Dreyer; Ibrahim, Fuad Moraes; Malki, Leonardo Tannus; de Paula Bichuete, Marina; de Paula Martins, Wellington; Rocha, Eduardo Melani

    2012-01-01

    Fungi are a major cause of keratitis, although few medications are licensed for their treatment. The aim of this study is to observe the variation in commercialisation of antifungal eye drops, and to predict the seasonal distribution of fungal keratitis in Brazil. Data from a retrospective study of antifungal eye drops sales from the only pharmaceutical ophthalmologic laboratory, authorized to dispense them in Brazil (Opthalmos) were gathered. These data were correlated with geographic and seasonal distribution of fungal keratitis in Brazil between July 2002 and June 2008. A total of 26,087 antifungal eye drop units were sold, with a mean of 2.3 per patient. There was significant variation in antifungal sales during the year (phumidity and antifungal drug sales (R2 = 0.17,p<0.01). Antifungal eye drops sales suggest that there is a seasonal distribution of fungal keratitis. A possible interpretation is that the third quarter of the year (a period when the climate is drier), when agricultural activity is more intense in Brazil, suggests a correlation with a higher incidence of fungal keratitis. A similar model could be applied to other diseases, that are managed with unique, or few, and monitorable medications to predict epidemiological aspects.

  17. A New Method to Predict the Epidemiology of Fungal Keratitis by Monitoring the Sales Distribution of Antifungal Eye Drops in Brazil

    Science.gov (United States)

    Ibrahim, Marlon Moraes; de Angelis, Rafael; Lima, Acacio Souza; Viana de Carvalho, Glauco Dreyer; Ibrahim, Fuad Moraes; Malki, Leonardo Tannus; de Paula Bichuete, Marina; de Paula Martins, Wellington; Rocha, Eduardo Melani

    2012-01-01

    Purpose Fungi are a major cause of keratitis, although few medications are licensed for their treatment. The aim of this study is to observe the variation in commercialisation of antifungal eye drops, and to predict the seasonal distribution of fungal keratitis in Brazil. Methods Data from a retrospective study of antifungal eye drops sales from the only pharmaceutical ophthalmologic laboratory, authorized to dispense them in Brazil (Opthalmos) were gathered. These data were correlated with geographic and seasonal distribution of fungal keratitis in Brazil between July 2002 and June 2008. Results A total of 26,087 antifungal eye drop units were sold, with a mean of 2.3 per patient. There was significant variation in antifungal sales during the year (p<0.01). A linear regression model displayed a significant association between reduced relative humidity and antifungal drug sales (R2 = 0.17,p<0.01). Conclusions Antifungal eye drops sales suggest that there is a seasonal distribution of fungal keratitis. A possible interpretation is that the third quarter of the year (a period when the climate is drier), when agricultural activity is more intense in Brazil, suggests a correlation with a higher incidence of fungal keratitis. A similar model could be applied to other diseases, that are managed with unique, or few, and monitorable medications to predict epidemiological aspects. PMID:22457787

  18. In vitro antifungal activity against Candida species of Sri Lankan orthodox black tea (Camellia sinensis L. belonging to different agro-climatic elevations

    Directory of Open Access Journals (Sweden)

    Wanigasekara Daya Ratnasooriya

    2017-02-01

    Full Text Available Objective: To investigate the antifungal potential of different grades of Sri Lankan orthodox black tea [orange pekoe, broken orange pekoe fannings (BOPF and Dust No. 1] belonging to the three agro-climatic elevations (low, mid and high. Methods: Antifungal activity was assessed in vitro using methanolic extracts (300 µg/disc and agar disc diffusion bioassay technique against three Candida species, Candida albicans (C. albicans, Candida glabrata (C. glabrata, and Candida tropicalis. ketoconazole and itraconazole mixture was used as positive control (10 µg/disc and methanol was used as the negative control. The minimum inhibitory concentrations were also determined using standard protocols. Results: None of the extracts were effective against Candida tropicalis. Furthermore, orange pekoe grade tea belonging to all agro-climatic elevations did not induce any antifungal activity against C. albicans and C. glabrata as well. Conversely, Dust No. 1 belonging to all three agro-climatic elevations and low-grown BOPF showed moderate antifungal activity against C. albicans and C. glabrata. Interestingly, the severity of the antifungal effect varied with agroclimatic elevations. The minimum inhibitory concentrations ranged from 64.00–128.00 µg/mL against C. glabrata and 128.00-256.00 µg/mL against C. albicans. Conclusions: Sri Lankan Dust No. 1 and BOPF have marked antifungal activity in vitro and offer promise to be used as a supplementary beverage in prophylaxis and during drug treatment in candidiasis.

  19. Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA nanoparticles in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Tang X

    2014-11-01

    Full Text Available Xiaolong Tang,1,2,* He Zhu,3,* Ledong Sun,4,* Wei Hou,2 Shuyu Cai,1 Rongbo Zhang,1 Feng Liu5 1Stem Cell Engineering Research Center, School of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Institute of Skin Damage and Repair, General Hospital of Beijing Military Command, Beijing, People’s Republic of China; 4Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Anesthesiology, Children’s Hospital, Chongqing Medical University; Key Laboratory of Child Development and Disorders of the Ministry of Education, Chongqing, People’s Republic of China *These authors contributed equally to this work Background: Amphotericin B (AMB is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs – diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide (PLGA-TPGS – have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs and evaluate their antifungal effects in vitro and in vivo.Methods: AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo.Results: AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual

  20. Comparison of the activities of four antifungal agents in an in vitro model of dermatophyte nail infection

    Directory of Open Access Journals (Sweden)

    Nowrozi Hossein

    2008-01-01

    Full Text Available Background: Onychomycosis is a difficult condition to treat and cure rates are disappointing. Moreover fungicidal action of antifungal agents in NCCLS assays and their rapid accumulation in nails in vivo are not compatible with the duration of treatment. Aims: This study aimed to find the effectiveness of 4 different antifungal agents in an in vitro model with some similarities to in vivo conditions. Materials and Methods: Strains of Trichophyton rubrum I-III, Trichophyton mentagrophytes (usual form, Trichophyton mentagrophytes 73, Epidermophyton Flucosom, Microsporum Canis, and Trichophyton Schoenleini which were isolated from the nails of patients, were hired. Inocula suspensions were prepared from 7 to 14 day-old cultures of dermatophytes. Antifungal agents including fluconazole, ketoconazole, terbinafine, and griseofulvin were obtained as standard powders. For each antifungal agent, initial MIC was calculated by registering the optical density for 10 two-fold serially diluted forms which was incubated with diluted fungal suspensions with RPMI 1640. Human nail powder inoculated with different strains and incubated in RPMI 1640 and different concentrations of antifungal drugs for 4 weeks. Final MIC at different steps of 1, 2, 3 and 4 weeks were investigated. Results: The final MIC that resulted from the incubation of dermatophytes with nail powder was much more than the initial which was concluded from conventional MIC assay. Terbinafine had the lowest rate of initial and final MICs. Conclusion: The model described here may present more similar conditions to clinical fungal infections; therefore the results such as MIC may be more helpful for hiring the most effective antifungal agent.

  1. Synthesis, Single Crystal X-ray Analysis, and Antifungal Profiling of Certain New Oximino Ethers Bearing Imidazole Nuclei

    Directory of Open Access Journals (Sweden)

    Reem I. Al-Wabli

    2017-11-01

    Full Text Available Fungal infections threaten human health, particularly in immune-compromised patients worldwide. Although there are a large number of antifungal agents available, the desired clinical attributes for the treatment of fungal infections have not yet been achieved. Azoles are the mainstay class of the clinically used antifungal agents. In the current study, the synthesis, spectroscopic characterization, and antifungal activity of certain new oximino ethers Va–n bearing imidazole nuclei are reported. The (E-configuration of the imine double bond of the synthesized compounds Va–n has been confirmed via single crystal X-ray analysis of compound Vi as a representative example of this class of compounds. The molecular structure of compound Vi was crystallized in the monoclinic, P21/c, a = 18.7879(14 Å, b = 5.8944(4 Å, c = 16.7621(12 Å, β = 93.063(3°, V = 1855.5(2 Å3, Z = 4. The in vitro antifungal activity of the synthesized compounds Va–n were evaluated using diameter of the inhibition zone (DIZ and minimum inhibitory concentration (MIC assays against different fungal strains. Compound Ve manifested anti-Candida albicans activity with an MIC value of 0.050 µmol/mL, being almost equipotent with the reference antifungal drug fluconazole (FLC,while compounds Vi and Vn are the most active congeners against Candida parapsilosis, being equipotent and about twenty-three times more potent than FLC with an MIC value of 0.002 µmol/mL. The results of the current report might support the development of new potent and safer antifungal azoles.

  2. Chemical modification of antifungal polyene macrolide antibiotics

    International Nuclear Information System (INIS)

    Solovieva, S E; Olsufyeva, E N; Preobrazhenskaya, M N

    2011-01-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  3. Nylon-3 polymers with selective antifungal activity.

    Science.gov (United States)

    Liu, Runhui; Chen, Xinyu; Hayouka, Zvi; Chakraborty, Saswata; Falk, Shaun P; Weisblum, Bernard; Masters, Kristyn S; Gellman, Samuel H

    2013-04-10

    Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for Candida albicans ) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis).

  4. Therapeutic drug monitoring of antimicrobials.

    Science.gov (United States)

    Balakrishnan, Indran; Shorten, Robert J

    2016-05-01

    As pathology services become more centralized and automated, the measurement of therapeutic antimicrobial drugs concentrations is increasingly performed in clinical biochemistry or 'blood science' laboratories. This review outlines key groups of antimicrobial agents: aminoglycosides, glycopeptides, antifungal agents and antituberculosis agents, their role in managing infectious diseases, and the reasons why serum concentration measurement is important. © The Author(s) 2016.

  5. Antifungal activity of different extracts of Ageratum conyzoides for the ...

    African Journals Online (AJOL)

    Antifungal activity of different extracts of Ageratum conyzoides for the management of Fusarium solani. Sidra Javed, Uzma Bashir. Abstract. Ageratum conyzoides L. is potential allelopathic weed very useful for its antifungal and antimicrobial activity. Being environmentally safe and friendly, it has the potential to substitute ...

  6. Cuticular antifungals in spiders: density- and condition dependence.

    Directory of Open Access Journals (Sweden)

    Daniel González-Tokman

    Full Text Available Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities. For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders.

  7. In vitro antifungal activity of Dorstenia mannii leaf extracts (Moraceae)

    African Journals Online (AJOL)

    Owner

    The active ingredients of this plant could be an addition to the antifungal arsenal to opportunistic fungal yeast pathogens. Key words: Antifungal activity, Dorstenia mannii, yeasts, opportunistic candidiasis. INTRODUCTION. Nowadays, fungal diseases have emerged and are being increasingly recognized as important public ...

  8. Antifungal activity of extracts and phenolic compounds from ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-17

    Jun 17, 2009 ... (naringin, rutin, luteolin and kaempferol). The results of present study provide scientific basis for the use of the plant extract in the future development as antifungal, antibacterial, antioxidant and anti- inflammatory agent. Key words: Barringtonia racemosa, antifungal, HPLC, phenolic acids, flavonoids.

  9. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Science.gov (United States)

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  10. In vitro control of Alternaria citri using antifungal potentials of ...

    African Journals Online (AJOL)

    In vitro control of Alternaria citri using antifungal potentials of Trichoderma species. Asma Murtaza, Shazia Shafique, Tehmina Anjum, Sobiya Shafique. Abstract. The antifungal potential of five species of Trichoderma viz., Trichoderma viride, Trichoderma aureoviride, Trichoderma reesei, Trichoderma koningii and ...

  11. [Derivatives of 4-nitroso-aminopyrazole as antifungal agents].

    Science.gov (United States)

    Giori, P; Mazzotta, D; Vertuani, G; Guarneri, M; Pancaldi, D; Brunelli, A

    1981-12-01

    The synthesis of 4-nitroso-5-amminopyrazoles and of 4-nitroso-5-pyrazolylurethans and -ureas is described. The chemicals were tested for antifungal activity against Erysiphe graminis, Erysiphe cichoracearum, Puccinia recondita, Septoria apii and Rhizoctonia solani. A number of the described compounds showed some antifungal activity.

  12. Antifungal Activity of Endemic Salvia tigrina in Turkey | Dulger ...

    African Journals Online (AJOL)

    Ketoconazole was used as a positive reference standard to determine the sensitivity of the strains. Results: The minimum inhibitory concentration (MIC) ranged from 3.12 to 25 mg/mL. All the extracts exhibited a strong antifungal effect against the fungal cultures. The extracts exhibited greater antifungal effect against C.

  13. IIn vitro antifungal evaluation of various plant extracts against early ...

    African Journals Online (AJOL)

    Antifungal activities of 27 plant extracts were tested against Alternaria solani (E. & M.) Jones and Grout using radial growth technique. While all tested plant extracts produced some antifungal activities, the results revealed that Circium arvense, Humulus lupulus, Lauris nobilis and Salvia officinalis showed significant ...

  14. Identification and antifungal activity of Streptomyces sp. S72 isolated ...

    African Journals Online (AJOL)

    The test of antifungal activity for several pathogens fungi causing invasive aspergillosis and systemic candidiasis revealed that the Streptomyces sp. S72 was a good moderate antifungal compound producer against Aspergillus fumigatus and Candida albicans, and had no activity against Aspergillus flavus, Aspergillus ...

  15. In vitro Antifungal, Antioxidant and Cytotoxic Activities of a Partially ...

    African Journals Online (AJOL)

    Purpose: To determine the in vitro antifungal and antioxidant activities of the aqueous extract and protein fraction of Atlantia monophylla Linn (Rutaceae) leaf. Methods: Ammonium sulphate (0 – 80 %) precipitation method was used to extract protein from the leaves of A. monophylla Linn (Rutaceae). In vitro antifungal ...

  16. Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis.

    Science.gov (United States)

    Saldanha, Camila Arruda; Garcia, Mônica Pereira; Iocca, Diego Cesar; Rebelo, Luciana Guilherme; Souza, Ana Camila Oliveira; Bocca, Anamélia Lorenzetti; Almeida Santos, Maria de Fátima Menezes; Morais, Paulo Cesar; Azevedo, Ricardo Bentes

    2016-06-01

    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications.

  17. Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Camila Arruda Saldanha

    2016-06-01

    Full Text Available This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications.

  18. Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin

    International Nuclear Information System (INIS)

    Neuhof, Torsten; Seibold, Michael; Thewes, Sascha; Laue, Michael; Han, Chang-Ok; Hube, Bernhard; Doehren, Hans von

    2006-01-01

    This is First report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 μg/ml, independently from the species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different

  19. Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana.

    Science.gov (United States)

    Eilenberg, Haviva; Pnini-Cohen, Smadar; Rahamim, Yocheved; Sionov, Edward; Segal, Esther; Carmeli, Shmuel; Zilberstein, Aviah

    2010-03-01

    Nepenthes spp. are carnivorous plants that have developed insect capturing traps, evolved by specific modification of the leaf tips, and are able to utilize insect degradation products as nutritional precursors. A chitin-induced antifungal ability, based on the production and secretion to the trap liquid of droserone and 5-O-methyldroserone, is described here. Such specific secretion uniquely occurred when chitin injection was used as the eliciting agent and probably reflects a certain kind of defence mechanism that has been evolved for protecting the carnivory-based provision of nutritional precursors. The pitcher liquid containing droserone and 5-O-methyldroserone at 3:1 or 4:1 molar ratio, as well as the purified naphthoquinones, exerted an antifungal effect on a wide range of plant and human fungal pathogens. When tested against Candida and Aspergillus spp., the concentrations required for achieving inhibitory and fungicidal effects were significantly lower than those causing cytotoxicity in cells of the human embryonic kidney cell line, 293T. These naturally secreted 1,4-naphthoquinone derivatives, that are assumed to act via semiquinone enhancement of free radical production, may offer a new lead to develop alternative antifungal drugs with reduced selectable pressure for potentially evolved resistance.

  20. In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia.

    Science.gov (United States)

    James, Jasper Elvin; Santhanam, Jacinta; Lee, Mei Chen; Wong, Choon Xian; Sabaratnam, Parameswari; Yusoff, Hamidah; Tzar, Mohd Nizam; Razak, Mohd Fuat Abdul

    2017-04-01

    Neoscytalidium dimidiatum is an opportunistic fungus causing cutaneous infections mostly, which are difficult to treat due to antifungal resistance. In Malaysia, N. dimidiatum is associated with skin and nail infections, especially in the elderly. These infections may be mistaken for dermatophyte infections due to similar clinical appearance. In this study, Neoscytalidium isolates from cutaneous specimens, identified using morphological and molecular methods (28 Neoscytalidium dimidiatum and 1 Neoscytalidium sp.), were evaluated for susceptibility towards antifungal agents using the CLSI broth microdilution (M38-A2) and Etest methods. Amphotericin B, voriconazole, miconazole and clotrimazole showed high in vitro activity against all isolates with MIC ranging from 0.0313 to 1 µg/mL. Susceptibility towards fluconazole and itraconazole was noted in up to 10% of isolates, while ketoconazole was inactive against all isolates. Clinical breakpoints for antifungal drugs are not yet available for most filamentous fungi, including Neoscytalidium species. However, the results indicate that clinical isolates of N. dimidiatum in Malaysia were sensitive towards miconazole, clotrimazole, voriconazole and amphotericin B, in vitro.

  1. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.

    Science.gov (United States)

    Doğan, İnci Selin; Saraç, Selma; Sari, Suat; Kart, Didem; Eşsiz Gökhan, Şebnem; Vural, İmran; Dalkara, Sevim

    2017-04-21

    Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0.25 μg/mL), were potent against resistant C. glabrata, a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action, we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Oxylipin studies expose aspirin as antifungal.

    Science.gov (United States)

    Kock, Johan L F; Sebolai, Olihile M; Pohl, Carolina H; van Wyk, Pieter W J; Lodolo, Elizabeth J

    2007-12-01

    The presence of aspirin-sensitive 3-hydroxy fatty acids (i.e. 3-OH oxylipins) in yeasts was first reported in the early 1990s. Since then, these oxidized fatty acids have been found to be widely distributed in yeasts. 3-OH oxylipins may: (1) have potent biological activity in mammalian cells; (2) act as antifungals; and (3) assist during forced spore release from enclosed sexual cells (asci). A link between 3-OH oxylipin production, mitochondria and aspirin sensitivity exists. Research suggests that: (1) 3-OH oxylipins in some yeasts are probably also produced by mitochondria through incomplete beta-oxidation; (2) aspirin inhibits mitochondrial beta-oxidation and 3-OH oxylipin production; (3) yeast sexual stages, which are probably more dependent on mitochondrial activity, are also characterized by higher 3-OH oxylipin levels as compared to asexual stages; (4) yeast sexual developmental stages as well as cell adherence/flocculation are more sensitive to aspirin than corresponding asexual growth stages; and (5) mitochondrion-dependent asexual yeast cells with a strict aerobic metabolism are more sensitive to aspirin than those that can also produce energy through an alternative anaerobic glycolytic fermentative pathway in which mitochondria are not involved. This review interprets a wide network of studies that reveal aspirin to be a novel antifungal.

  3. Antifungal Quinoline Alkaloids from Waltheria indica.

    Science.gov (United States)

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy.

  4. Prospects of application of vegetable oils as antifungal agents (Literature review

    Directory of Open Access Journals (Sweden)

    A. A. Mikheev

    2017-04-01

    Full Text Available Purpose of work – to summarize and present modern scientific literature reviews of alternative antifungal agents usage, among which herbal medicines, and in particular herbal oils, may play significant role. Fungal infections (mycoses are one of the leading infectious diseases in the world. Besides the medical importance, pathogenic fungi play a significant role in the food industry as potential pollutants. In order to treat fungal infections and to prevent food spoilage various medications that are products of chemical synthesis are widely used and the need for them increases significantly. However, among large number of medications and herbal drugs only a small part is used to treat fungal infections and to prevent food decay, though plants contain a lot of bioactive compounds with potential antifungal properties. Therefore, question of application of vegetable oils as antifungal agents is relevant. Various plants contain oils that have the potential antifungal properties, but are often used only in gastronomic purpose. The same time those oils can be successfully used for the treatment of candidiasis and infections caused by fungi of genera Aspergillus, Trichoderma, Penicillium, Fusarium, Metrhizium, Ophiostoma, Scopulariopsis and others. Their effects are manifested like using a single vegetable oil and mixtures of oils. Conclusions. Vegetable oils usage has big perspectives due to the lack of «addictive» effect and the development of resistance in fungi of different taxa. Vegetable oils do not require considerable investments for their reception, and thanks to traditions of aromo- and herbal medicine, their usage can be more effective in contrast to traditional chemotherapeutic agents. The search and study of new medicines based on vegetable oils may be a perspective direction of modern microbiological sciences and requires further deep studies of their biological properties and mechanisms of action.

  5. Initial antifungal strategy does not correlate with mortality in patients with candidemia.

    Science.gov (United States)

    Murri, R; Scoppettuolo, G; Ventura, G; Fabbiani, M; Giovannenze, F; Taccari, F; Milozzi, E; Posteraro, B; Sanguinetti, M; Cauda, R; Fantoni, M

    2016-02-01

    The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.

  6. Successful empirical antifungal therapy of intravenous itraconazole with pharmacokinetic evidence in pediatric cancer patients undergoing hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kim, Hyery; Shin, Donghoon; Kang, Hyoung Jin; Yu, Kyung-Sang; Lee, Ji Won; Kim, Sung Jin; Kim, Min Sun; Song, Eun Sun; Jang, Mi Kyoung; Park, June Dong; Jang, In-Jin; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop

    2015-07-01

    Empirical antifungal therapy prevents invasive fungal infections in patients with cancer. This study assessed the empirical efficacy of intravenous itraconazole in pediatric patients undergoing hematopoietic stem cell transplantation, and investigated the pharmacokinetics and clinical implications. Oral itraconazole syrup was started (2.5 mg/kg twice daily) for prophylaxis, and patients with persistent neutropenic fever for more than 2 days were switched to intravenous itraconazole (5 mg/kg twice daily for 2 days for induction and 5 mg/kg daily for maintenance) as empirical treatment. Empirical antifungal efficacy was assessed retrospectively in 159 transplantations, and a full pharmacokinetic study was prospectively conducted in six of these patients. Successful antifungal efficacy was defined as the fulfillment of all components of a five-part composite end point. The overall empirical antifungal success rate fulfilling all criteria was 42.1 %. No death or drug-related serious adverse events occurred during the study. Mean trough plasma concentration of itraconazole after oral prophylaxis and intravenous induction were 577.2 and 1659.7 μg/L, respectively. Mean area under the concentration-time curve of itraconazole and its metabolite at steady state were 42,837 ± 24,746 μg·h/L and 63,094 ± 19,255 μg·h/L. Intravenous itraconazole was effective and safe as an empirical antifungal agent in pediatric patients; this was due to the fast and satisfactory increase in drug concentration by switching from oral to intravenous therapy.

  7. 2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan

    Directory of Open Access Journals (Sweden)

    Hsiang-Chi Kung

    2018-02-01

    Full Text Available The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug–drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.

  8. Bibliometric analysis of literature on antifungal triazole resistance: 1980 – 2015

    Science.gov (United States)

    Sweileh, Waleed M.; Sawalha, Ansam F.; Al-Jabi, Samah; Zyoud, Sa’ed H.

    2017-01-01

    Background Triazole antifungal agents play an important role in the treatment of a wide range of fungal infections. Little is known about antifungal triazole drug resistance when compared to antibiotic resistance. Therefore, this study was carried out to give a bibliometric overview of literature on triazole antifungal drug resistance. Methods Keywords related to triazole drug class and resistance were used in a search query in the Scopus search engine. The time span was set from 1980 to 2015. Data pertaining to growth of publications, the most active countries and institutions, the most cited articles, and mapping of molecular mechanisms of resistance were analyzed. Results A total of 1648 journal articles were retrieved with an average of 20.46 citations per article. Annual growth of triazole resistance showed an increasing pattern during the study period. The United States of America (n=446; 27.06%) ranked first in productivity followed by the United Kingdom (UK) (n=176; 10.68%), and China (n=133; 8.07%). Radboud University Nijmegen Medical Centre (n=69, 4.19%) in the Netherlands ranked first in productivity, while the journal Antimicrobial Agents and Chemotherapy ranked first (n=255; 15.47%) in publishing articles on triazole resistance. Mapping mechanisms of resistance showed that efflux pump and mutations in target enzyme are major mechanisms described in resistance to triazoles. Conclusion There was a growth of publications on triazole resistance in the past two decades with the bulk of publications on triazole resistance in Candida species. The data presented here will serve as baseline information for future comparative purposes. PMID:28331838

  9. Antifungal susceptibility of bloodstream Candida isolates in Sfax hospital: Tunisia.

    Science.gov (United States)

    Sellami, A; Sellami, H; Néji, S; Makni, F; Abbes, S; Cheikhrouhou, F; Chelly, H; Bouaziz, M; Hammami, B; Ben Jemaa, M; Khaled, S; Ayadi, A

    2011-06-01

    Invasive candidiasis has emerged as an important nosocomial infection, causing significant morbidity and mortality especially among critically ill patients. The aim of our study was to determine specie distribution and resistance profiles of Candida species isolated from blood cultures. We conducted a retrospective study of all episodes of candidemia diagnosed in our laboratory from January 2006 to May 2009. The susceptibility to antifungal agents of all Candida isolates was tested by using a Sensititre(®) YeastOne panel. A total of 130 Candida isolates were recovered from blood cultures. Candida tropicalis was the most frequent specie (37.7%), followed by C. albicans (22.3%), C. glabrata (19.2%), and C. parapsilosis (12.2%). All the isolates were inhibited by ≤1 μg/ml of amphotericin B and ≤2 μg/ml of caspofungin. For fluconazole, 7.3% of clinical isolates were resistant. It was most active against C. parapsilosis (100% susceptible), C. albicans (95.8% susceptible), and C. tropicalis (94% susceptible). All of the fluconazole-susceptible isolates were susceptible to voriconazole, as were 83.3% of the fluconazole-susceptible-dose-dependent isolates. Among fluconazole-resistant isolates, 85.7% were susceptible to voriconazole. In our institution, C. tropicalis was the most frequent specie isolated from the bloodstream. Caspofungin had an excellent in vitro activity against Candida isolates and was the drug of choice among fluconazole-resistant isolates. © Springer Science+Business Media B.V. 2010

  10. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

    2016-09-30

    Fusarium head blight (FHB), primarily caused by Fusarium graminearum , is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum , such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  11. Antifungal Activity of Copaifera langsdorffii Desf Oleoresin against Dermatophytes

    Directory of Open Access Journals (Sweden)

    Nádia R. B. Raposo

    2013-10-01

    Full Text Available Dermatophytoses are mycoses that affect keratinized tissues in both humans and animals. The aim of this study was to investigate the antifungal activity of the oleoresin extracted from Copaifera langsdorffii Desf. against the strains Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 11481 and Trichophyton rubrum CCT 5507. The antimicrobial activity was determined by minimum inhibitory concentration (MIC and minimum fungicidal concentration (MFC values. Ketoconazole and terbinafine were used as reference drugs. The copaiba oleoresin showed moderate fungicidal activity against T. mentagrophytes ATCC 11481 (MIC and MFC = 170 μg mL−1 and weak fungicidal activity against T. rubrum CCT 5507 (MIC = 1,360 μg mL−1 and MFC = 2,720 μg mL−1. There was no activity against M. canis ATCC 32903 and M. gypseum ATCC 14683. SEM analysis revealed physical damage and morphological alterations such as compression and hyphae clustering in the structure of the fungi exposed to the action of the oleoresin. The results stimulate the achievement of in vivo assays to confirm the benefits of the application of oleoresin extracted from copaiba in the treatment of dermatophytosis, both in humans and in animals.

  12. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Miroslava Cuperlovic-Culf

    2016-09-01

    Full Text Available Fusarium head blight (FHB, primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  13. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

    Science.gov (United States)

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-01-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

  14. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.

    Directory of Open Access Journals (Sweden)

    Ikechukwu Okoli

    2009-09-01

    Full Text Available Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.

  15. [Evaluation of antifungal and mollusuicidial activities of Moroccan Zizyphus lotus (L.) Desf].

    Science.gov (United States)

    Lahlou, M; El Mahi, M; Hamamouchi, J

    2002-11-01

    Zizyphus lotus (L.) Desf. is one of the traditional drugs commonly used in folk medicine in Morocco. Extracts obtained from the successive exhaustion in petroleum ether, chloroform, ethyl acetate and methanol were in vitro found active either against nine pathogenic fungi and Bulinus truncatus, the intermediate host and vector of transmission of unitary schistosomiasis in Morocco. Particularly, the chloroform extract appears the most interesting in antifungal tests at lowest concentrations because of its countenance on terpenic compounds. Whereas, methanolic extract was found to possess the strong mollusuicidial activity and exhibited potent "knock-down" effect on molluscans related to its countenance on saponins.

  16. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

    Directory of Open Access Journals (Sweden)

    Ronald P. Haff

    2013-01-01

    Full Text Available Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA, a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2, tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

  17. Antifungal Activity of Brazilian Propolis Microparticles against Yeasts Isolated from Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Kelen Fátima Dalben Dota

    2011-01-01

    Full Text Available Propolis, a resinous compound produced by Apis mellifera L. bees, is known to possess a variety of biological activities and is applied in the therapy of various infectious diseases. The aim of this study was to evaluate the in vitro antifungal activity of propolis ethanol extract (PE and propolis microparticles (PMs obtained from a sample of Brazilian propolis against clinical yeast isolates of importance in the vulvovaginal candidiasis (VVC. PE was used to prepare the microparticles. Yeast isolates (n=89, obtained from vaginal exudates of patients with VVC, were exposed to the PE and the PMs. Moreover, the main antifungal drugs used in the treatment of VVC (Fluconazole, Voriconazole, Itraconazole, Ketoconazole, Miconazole and Amphotericin B were also tested. Minimum inhibitory concentration (MIC was determined according to the standard broth microdilution method. Some Candida albicans isolates showed resistance or dose-dependent susceptibility for the azolic drugs and Amphotericin B. Non-C. albicans isolates showed more resistance and dose-dependent susceptibility for the azolic drugs than C. albicans. However, all of them were sensitive or dose-dependent susceptible for Amphotericin B. All yeasts were inhibited by PE and PMs, with small variation, independent of the species of yeast. The overall results provided important information for the potential application of PMs in the therapy of VVC and the possible prevention of the occurrence of new symptomatic episodes.

  18. Tioconazole, a new imidazole-antifungal agent for the treatment of dermatomycoses. Antifungal and pharmacologic properties.

    Science.gov (United States)

    Marriott, M S; Baird, J R; Brammer, K W; Faulkner, J K; Halliwell, G; Jevons, S; Tarbit, M H

    1983-01-01

    Tioconazole is a new imidazole antifungal agent with broad-spectrum activity. Its in vitro activity against common dermal pathogens is generally better than miconazole by a factor of 2-8. This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. Pharmacokinetic studies in animals have demonstrated minimal systemic exposure following dermal application. Acute general pharmacology studies have shown that the compound is well tolerated in animals and unlikely to produce side-effects in man.

  19. Antibacterial and antifungal activities of andrachne cordifolia muell.

    Science.gov (United States)

    Ahmad, Bashir; Hassan Shah, S M; Bashir, Shumaila; Nisar, Muhammad; Chaudry, M Iqbal

    2007-12-01

    The crude methanolic extract of Andrachne cordifolia Muell. (Euphorbiaceae) and its various fractions in different solvent systems (chloroform, ethyl acetate and n-butanol) were screened for antibacterial and antifungal activities. Crude extract and subsequent fractions demonstrated moderate to excellent antibacterial activities against the tested pathogens. Highest antibacterial activity was displayed by both chloroform and ethyl acetate fractions (100%) followed by the crude extract (68%) against Salmonella typhi. Similarly, crude extract and its subsequent fractions showed mild to excellent activities in antifungal bioassay with maximum (76%) antifungal activity against Microsporum canis by the chloroform fraction followed by the crude extract (65%).

  20. In vitro Antifungal Activity of Limonene against Trichophyton rubrum

    OpenAIRE

    Chee, Hee Youn; Kim, Hoon; Lee, Min Hee

    2009-01-01

    In this study, the antifungal activities of limonene against Trichophyton rubrum were evaluated via broth microdilution and vapor contact assays. In both assays, limonene was shown to exert a potent antifungal effect against T. rubrum. The volatile vapor of limonene at concentrations above 1 ?l/800 ml air space strongly inhibited the growth of T. rubrum. The MIC value was 0.5% v/v in the broth microdilution assay. The antifungal activity of limonene against T. rubrum was characterized as a fu...

  1. Design, synthesis, and in vitro evaluation of novel antifungal triazoles.

    Science.gov (United States)

    Xie, Fei; Ni, Tingjunhong; Zhao, Jing; Pang, Lei; Li, Ran; Cai, Zhan; Ding, Zichao; Wang, Ting; Yu, Shichong; Jin, Yongsheng; Zhang, Dazhi; Jiang, Yuanying

    2017-05-15

    Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Most of the compounds exhibited potent in vitro antifungal activities against 8 fungal isolates. Especially, compounds a10, a13, and a14 exhibited superior or comparable antifungal activity to ravuconazole against all the tested fungi. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole moiety of ravuconazole with fluorophenylisoxazole resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Anti-fungal activity of irradiated chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Pham ThiLe Ha; Tran Thi Thuy; Nguyen Quoc Hien [Nuclear Research Inst., No.1 Nguyen Tu Luc, Dalat (Viet Nam); Nagasawa, Naotsugu; Kume, Tamikazu [Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Gunma (Japan)

    1999-09-01

    Anti-fungal activity of chitosan induced by irradiation has been investigated. Commercial chitosan samples of 8B (80% deacetylation) and l0B (99% deacetylation) were irradiated by {gamma}-ray in dry condition. Highly deacethylated chitosan (10B) at low dose irradiation (75 kGy) was effective for inhibition of fungal growth. The sensitivities of Exobasidium vexans, Septoria chrysanthemum and Gibberella fujikuroi for the irradiated chitosan were different and the necessary concentrations of chitosan were 550, 350 and 250 {mu}g/ml, respectively. For the plant growth, low deacethylation (chitosan 8B) and high dose (500 kGy) was effective and the growth of chrysanthemum was promoted by spraying the irradiated chitosan. (author)

  3. Antifungal potential of Indian medicinal plants.

    Science.gov (United States)

    Dabur, Rajesh; Singh, H; Chhillar, A K; Ali, M; Sharma, G L

    2004-06-01

    Fourteen Indian plants, selected based on their use in respiratory and other disorders in traditional systems of medicine, were analyzed for their potential activity against fungi. The antifungal activity was investigated by disc diffusion, microbroth dilution and percent spore germination inhibition tests against pathogenic Aspergilli. Methanolic extracts of Solanum xanthocarpum and Datura metel inhibited the growth of Aspergillus fumigatus, A. flavus and A. niger and their in vitro MICs were found to be 1.25-2.50 mg/ml by both microbroth dilution and percent spore germination assays. In disc diffusion assay, a concentration of 0.062 mg/disc of methanol extract of D. metel showed significant activity against Aspergilli. S. xanthocarpum exhibited similar activity at 0.125 mg/disc. Copyright 2004 Elsevier B.V.

  4. Naturally occurring antifungal aromatic esters and amides

    International Nuclear Information System (INIS)

    Ali, M.S.; Shahnaz; Tabassum, S.; Ogunwande, I.A.; Pervez, M.K.

    2010-01-01

    During the search of antifungal natural products from terrestrial plants, a new long chained aromatic ester named grandiflorate along with spatazoate from Portulaca grandiflora and N-[2-methoxy-2-(4-methoxyphenyl) ethyl]-trans-cinnamide and aegeline from Solanum erianthum of Nigeria were isolated and tested against six fungal species. The known constituents have not been reported so far from mentioned investigated plants. Structures of the isolated compounds were elucidated with the aid of spectroscopic techniques including two dimensional NMR experiments. Among the compounds, the esters found more potent than amides against Candida albicans and Aspergillus flavus. The new compound grandiflorate gave response against all tested fungal species while aegeline was found to give lowest inhibition during this study. (author)

  5. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    leading to drug recalcitrance is the formation of antifungal persister cells. These cells have wild-type genotype with the ability to survive exposure to antifungal agents due to changed membrane composition, upregulated stress response, and enhanced cell wall integrity. Knowledge of the mechanisms...... are quiescent in G0 of the cell cycle. This knowledge leads us to suggest that the identified shared drug-tolerance mechanisms of persister and quiescent cells may serve as a foundation for developing novel treatment strategies that are independent of growth mode against systemic fungal infections....

  6. Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA nanoparticles

    Directory of Open Access Journals (Sweden)

    Qiu L

    2015-02-01

    Full Text Available Lixin Qiu,1,2,* Bicheng Hu,1,4,* Hongbo Chen,2,3 Shanshan Li,5 Yuqian Hu,2,3 Yi Zheng,2,3 Xinxing Wu1 1Institute of Virology, School of Medicine, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People’s Republic of China; 3School of Life Sciences, Tsinghua University, Beijing, People’s Republic of China; 4The Clinical Laboratory, Wuhan No 1 Hospital, Wuhan, Hubei, People’s Republic of China; 5Department of Plant Pathology and Microbiology, Iowa State University, Ames, IA, USA *These authors contributed equally to this work Abstract: This research was conducted to formulate biodegradable itraconazole (ITZ-loaded d-a-tocopheryl polyethylene glycol 1000 succinate-b-poly(e-caprolactone-ran-glycolide (TPGS-b-(PCL-ran-PGA; TPP nanoparticles (NPs (designed as ITZ-loaded TPP NPs to improve antifungal efficacy. ITZ-loaded TPP NPs were prepared by a modified double-emulsion method, and their size distribution, morphology, zeta potential, drug encapsulation efficiency, drug-release profile, and antifungal effects were characterized. The cytotoxicity of ITZ-loaded-TPP NPs on HeLa cells and fibroblasts was measured using the 3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide (MTT method. The in vivo antifungal activity of ITZ-loaded-TPP NPs was examined in mice by administrating 5×105 colony forming units of Candida albicans through the tail vein. The survival rate and survival time of the mice was observed. The fungal count and pathology of lung tissue was analyzed. The data showed that ITZ-loaded-TPP NPs have size of 265±5.8 nm, zeta potential of -31±0.5 mV, high encapsulation efficiency (95%, and extended drug-release profile. ITZ-loaded-TPP NPs at a high concentration of 25 mg/mL had no

  7. Species distribution and antifungal susceptibility patterns of Candida isolates from a public tertiary teaching hospital in the Eastern Cape Province, South Africa.

    Science.gov (United States)

    Mnge, P; Okeleye, B I; Vasaikar, S D; Apalata, T

    2017-05-15

    Candida species are the leading cause of invasive fungal infections, and over the past decade there has been an increased isolation of drug resistant Candida species. This study aimed to identify the species distribution of Candida isolates and to determine their unique antifungal susceptibility and resistance patterns. During a cross-sectional study, 209 Candida isolates (recovered from 206 clinical samples) were collected and their species distribution was determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa) was used to determine minimum inhibitory concentrations (MICs) to azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes (amphotericin B) and flucytosine. Four species of Candida were isolated, of which C. albicans was the most frequent, isolated in 45.4% (95/209) of the isolates, followed by C. glabrata: 31.1% (65/209). The MICs of the different antifungal drugs varied amongst the species of Candida. From the 130 isolates tested for MICs, 90.77% (112/130) were susceptible to all antifungal drugs and 6.9% (9/130) of the isolates were multi-drug resistant. C. dubliniensis (n=2) isolates were susceptible to all the above mentioned antifungal drugs. There was no significant difference in species distribution amongst clinical specimens and between patients' genders (P>0.05). An increase in MIC values for fluconazole and flucytosine towards the resistance range was observed. To our knowledge, this is the first report on surveillance of Candida species distribution and antifungal susceptibility at a public tertiary teaching hospital in Eastern Cape, South Africa.

  8. Antifungal activity of a prenylated flavonoid from Dalea elegans against Candida albicans biofilms.

    Science.gov (United States)

    Peralta, Mariana Andrea; da Silva, María Angel; Ortega, María Gabriela; Cabrera, José Luis; Paraje, María Gabriela

    2015-10-15

    The continuing emergence of infections with antifungal resistant Candida strains requires a constant search for new antifungal drugs, with the plant kingdom being an important source of chemical structures. The present study investigated the antifungal effect of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-8-prenylpinocembrin (8PP, formerly 6PP), a natural prenylflavonoid, on Candida albicans biofilms, and compared this with an azole antifungal (fluconazole) by studying the cellular stress and antioxidant response. The fluconazole sensitive (SCa) and azole-resistant (RCa) C. albicans strains were used, with biofilm formation being studied using crystal violet (CV) and confocal scanning laser microscopy (CSLM). The minimal inhibitory concentration for sessile cells (SMIC) was defined as the concentration of antifungal that caused a 50% (SMIC 50) and 80% (SMIC 80) reduction of treated biofilms. The reactive oxygen species (ROS) were detected by the reduction of nitro blue tetrazolium (NBT), and reactive nitrogen intermediates (RNI) were determined by the Griess assay. The activities of the superoxide dismutase (SOD) and catalase (CAT) antioxidant enzymes and the total antioxidant capacity of the biofilms were measured by spectrophotometric methods. ROS accumulation was also detected inside biofilms by using the fluorogenic dye 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), which was visualized by CSLM. The SCa and RCa biofilms were strongly inhibited by 8PP at 100 µM (SMIC 80). We observed that cellular stress affected biofilms growth, resulting in an increase of ROS and also of reactive nitrogen intermediates (RNI), with SOD and CAT being increased significantly in the presence of 8PP. The basal level of the biofilm total antioxidant capacity was higher in RCa than SCa. Moreover, in SCa, the total antioxidant capacity rose considerably in the presence of both 8PP and fluconazole. Our data suggest that 8PP may be useful for the treatment of biofilm

  9. In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF).

    Science.gov (United States)

    Palicz, Zoltán; Jenes, Agnes; Gáll, Tamás; Miszti-Blasius, Kornél; Kollár, Sándor; Kovács, Ilona; Emri, Miklós; Márián, Teréz; Leiter, Eva; Pócsi, István; Csősz, Eva; Kalló, Gergő; Hegedűs, Csaba; Virág, László; Csernoch, László; Szentesi, Péter

    2013-05-15

    The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg⁻¹ daily, for 2 weeks. Even at the highest concentration--a concentration highly toxic in vitro for all affected molds used, animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Species distribution and antifungal susceptibility of candidemia at a multispecialty center in North India

    Directory of Open Access Journals (Sweden)

    Maria Thomas

    2016-01-01

    Full Text Available Introduction: Fungi have emerged as major opportunistic pathogens. Candida species account for nearly 96% of all opportunistic mycoses and is an important cause of bloodstream infections. There has been a progressive shift from the predominance of Candida albicans to nonalbicans Candida species as the major cause of candidemia all over the world. Resistance to antifungal drugs is more in nonalbicans Candida species. Hence, speciation and antifungal susceptibility testing is the need of the hour. Materials and Methods: This retrospective study was conducted in a multispecialty center in North India from January 1, 2014 to March 31, 2015. The blood culture samples that were positive for Candida species were processed further. Species identification was done by standard microbiological techniques. Antifungal drug susceptibility was done by disk diffusion method (Clinical and Laboratory Standards Institute M44-A2. Results: A total of 10893 samples were processed, 1440 (13.2% blood cultures were positive. Candida species was isolated from 105 (7.3% samples, of which 15 (14.3% were C. albicans and 90 (85.7% were nonalbicans Candida. Nonalbicans Candida included Candida tropicalis (50.5%, Candida glabrata (19.0%, Candida parapsilosis (14.3% and one isolate each of Candida guillermondi and Candida krusei. Majority of the Candida spp. isolates were resistant to clotrimazole (55.5% fluconazole (42% and itraconazole (69% and and ketoconazole (38%. All isolates were uniformly sensitive to amphotericin B. Conclusion: There is predominance of nonalbicans Candida species in hospital setting. A high index of suspicion, early diagnosis, and a prompt and appropriate therapy remains the cornerstone of treatment.

  11. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    Science.gov (United States)

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  12. Antifungal activity of extracts and phenolic compounds from ...

    African Journals Online (AJOL)

    Antifungal activity of extracts and phenolic compounds from Barringtonia racemosa L. (Lecythidaceae). NM Hussin, R Muse, S Ahmad, J Ramli, M Mahmood, MR Sulaiman, MYA Shukor, MFA Rahman, KNK Aziz ...

  13. A Lysozyme with Antifungal Activity from Pithecellobium dulce Seeds

    Directory of Open Access Journals (Sweden)

    Ploypat Niyomploy

    2011-01-01

    Full Text Available A protein of an apparent molecular mass of 14.4 kDa with antifungal activity was isolated from the seeds of Pithecellobium dulce using extraction with 100 mM Tris-HCl buffer (pH=8.0, precipitation with 80 % ammonium sulfate, and bioassay purification via Resource Q anion exchange chromatography and Superdex 200 gel filtration chromatography. The purified protein was putatively identified by tandem mass spectrometry with Mascot database searching, with the partial amino acid sequences showing a high degree of similarity to chicken egg white lysozyme. This putative plant lysozyme expressed antifungal activity with a rather high thermal stability of up to 80 °C for 15 min (at pH=8.0. It exerted an antifungal action towards Macrophomina phaseolina but displayed no antifungal activity against two other isolates, Phymatotrichopsis omnivora and Fusarium avenaceum.

  14. In vitro antifungal and cytotoxicity activities of selected Tanzanian ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antifungal and cytotoxic activities of four medicinal plants from Tanzania, namely, Mystroxylon aethiopicum, Lonchocarpus capassa, Albizia anthelmentica and Myrica salicifolia. Methods: The plant materials were subjected to extraction using dichloromethane, ethyl acetate and distilled water.

  15. Development of a 96-well catheter-based microdilution method to test antifungal susceptibility of Candida biofilms.

    Science.gov (United States)

    Nweze, Emeka I; Ghannoum, Adam; Chandra, Jyotsna; Ghannoum, Mahmoud A; Mukherjee, Pranab K

    2012-01-01

    Candida biofilms, which are often associated with device-related infections, including catheter-related bloodstream infections, are resistant to commonly used antifungal agents. Current microtitre (96-well) plate-based methods to determine the antifungal susceptibility of these biofilms do not involve clinically relevant substrates (e.g. catheters), and are not well suited for evaluating the surface topography and three-dimensional architecture of biofilms. We describe a simple, reproducible catheter-based microtitre plate method to form biofilms and evaluate their antifungal susceptibility. Biofilms were formed by Candida species on 5 mm catheter discs placed in microtitre plates and quantified using metabolic conversion of a formazan dye (XTT). The morphology, surface topography and three-dimensional architecture of these biofilms were evaluated by fluorescence, confocal scanning laser and scanning electron microscopy, respectively. The optimized XTT method was used to evaluate the antifungal susceptibility of formed Candida biofilms to fluconazole, voriconazole, itraconazole and anidulafungin. Maximum XTT activity was achieved within 90 min. All tested Candida strains formed robust biofilms on catheter discs at both 24 and 48 h (P = 0.66). Biofilms exhibited typical gross morphology, surface topography and architecture, and no difference in biofilm thickness (P = 0.37). The three tested azoles were not active against the biofilms (MIC ≥ 64 mg/L), but anidulafungin possessed potent activity against them (MIC = 0.063-0.125 mg/L). The developed method is simple, rapid and reproducible, and requires relatively small amounts of drug. It can be used to perform both high-resolution microscopic analysis of the topography and architecture of biofilms, and evaluation of their antifungal susceptibility.

  16. Design, Synthesis, DFT Study and Antifungal Activity of Pyrazolecarboxamide Derivatives

    Directory of Open Access Journals (Sweden)

    Jin-Xia Mu

    2016-01-01

    Full Text Available A series of novel pyrazole amide derivatives were designed and synthesized by multi-step reactions from phenylhydrazine and ethyl 3-oxobutanoate as starting materials, and their structures were characterized by NMR, MS and elemental analysis. The antifungal activity of the title compounds was determined. The results indicated that some of title compounds exhibited moderate antifungal activity. Furthermore, DFT calculations were used to study the structure-activity relationships (SAR.

  17. [Amides of amino acids and peptides as antifungal agents].

    Science.gov (United States)

    Giori, P; Vertuani, G; Mazzotta, D; Guarneri, M; Pancaldi, D; Brunelli, A

    1982-07-01

    The synthesis of pyrazolyl-amides of aminoacids and peptides is described. The chemicals were tested for antifungal activity against wheat powdery mildew (Erysiphe graminis DC.), cucumber powdery mildew (Erysiphe cichoracearum DC.), wheat brown rust (Puccinia recondita Rob. ex Desm. f. sp. tritici Erikss et Henn.), celery leaf spot (Septoria Apii Briosi ed Cav. Chest.) and collar rot (Rhizoctonia solani Kuhn). Some of these compounds showed antifungal activity.

  18. Identification of ten KB425796-A congeners from Paenibacillus sp. 530603 using an antifungal assay against Aspergillus fumigatus in combination with micafungin.

    Science.gov (United States)

    Kai, Hirohito; Yamashita, Midori; Takase, Shigehiro; Hashimoto, Michizane; Muramatsu, Hideyuki; Nakamura, Ikuko; Yoshikawa, Koji; Kanasaki, Ryuichi; Ezaki, Masami; Nitta, Kumiko; Watanabe, Masato; Inamura, Noriaki; Fujie, Akihiko

    2013-08-01

    The discovery and characterization of natural congeners is one approach for understanding the relationship between chemical structure and biological function. We recently isolated the novel antifungal metabolite KB425796-A produced by the recently isolated bacterium Paenibacillus sp. 530603. On the basis of morphological changes of Aspergillus fumigatus induced by KB425796-A in combination with micafungin, we developed a highly sensitive screening method for the specific detection of KB425796-A congeners. Using this method, we isolated ten congeners of KB425796-A, named KB425796-B, -C, -D, -E, -F, -G, -H, -I, -J and -K, which exhibited diverse antifungal potencies against A. fumigatus. One of the most potent congeners, KB425796-C, had antifungal activities against several micafungin-resistant infectious fungi. KB425796-C can be a potential drug candidate for treating micafungin-resistant fungal infections.

  19. Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

    Directory of Open Access Journals (Sweden)

    Bao-Ju Li

    2013-11-01

    Full Text Available A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50 of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study.

  20. Design, synthesis, antifungal activities and 3D-QSAR of new N,N'-diacylhydrazines containing 2,4-dichlorophenoxy moiety.

    Science.gov (United States)

    Sun, Na-Bo; Shi, Yan-Xia; Liu, Xing-Hai; Ma, Yi; Tan, Cheng-Xia; Weng, Jian-Quan; Jin, Jian-Zhong; Li, Bao-Ju

    2013-11-01

    A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study.

  1. Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Adriana Araujo de Almeida

    2013-06-01

    Full Text Available Introduction Hospital infections caused by Candida spp. are a leading cause of morbidity and mortality in hospitalized patients, particularly those that are critically ill or immunocompromised. In this study, the distribution of Candida species in isolates from the University Hospital of the Federal University at Grande Dourados and their in vitro susceptibility to antifungal drugs were analyzed. Methods Yeasts were phenotypically identified using classical methodologies. Antifungal susceptibility tests to amphotericin B and fluconazole were performed using the broth microdilution technique. Results A total of 50 Candida isolates were obtained from hospitalized patients during the study period. We analyzed yeast isolates from urine (n=31; 62%, blood (n=12; 24%, and tracheal secretions (n=7; 14%. The following Candida species were identified: C. tropicalis (n=21; 42%, C. albicans (n=18; 36%, C. glabrata (n=10; 20%, and C. krusei (n=1; 2%. Antifungal susceptibility tests demonstrated that C. albicans was susceptible to both antifungal agents. However, 31.2% of the non-C. albicans Candida isolates displayed dose-dependent susceptibility to fluconazole, and 3.1% were resistant to amphotericin B. Conclusions In contrast to previous reports, our results indicated that C. tropicalis was the most commonly isolated yeast species among the hospital patients. The predominance of non-C. albicans Candida infections confirms the importance of species-level identification for implementing appropriate antifungal therapies.

  2. Screening for antifungal activities of extracts of the brazilian seaweed genus Laurencia (Ceramiales, Rhodophyta

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    Erika M. Stein

    2011-05-01

    Full Text Available The resistance of pathogens to commonly used antibiotics has enhanced morbidity and mortality and has triggered the search for new drugs. Several species of the red alga genus Laurencia are very interesting candidates as potential sources of natural products with pharmaceutical activity because they are known to produce a wide range of chemically interesting halogenated secondary metabolites. This is an initial report of the antifungal activities of the secondary metabolites of five species of Laurencia, collected in the state of Espírito Santo, against three strains of pathogenic fungi: Candida albicans (CA, Candida parapsilosis (CP, and Cryptococcus neoformans (CN. Minimum inhibitory concentrations (MIC of the algal extracts were determined by serial dilution method in RPMI 1640 Medium in 96-well plates according to the NCCLS and microbial growth was determined by absorbance at 492nm. A result showing maintenance or reduction of the inoculum was defined as fungistatic, while fungicidal action was no observed growth in the 10 µL fungistatic samples subcultured in Sabouraud Agar. Our results indicate that apolar extracts of Laurencia species possess antifungal properties and encourage continued research to find new drugs for therapy of infectious diseases in these algae.

  3. Synthesis, antioxidant, antifungal, molecular docking and ADMET studies of some thiazolyl hydrazones.

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    Kauthale, Sushama; Tekale, Sunil; Damale, Manoj; Sangshetti, Jaiprakash; Pawar, Rajendra

    2017-08-15

    Some thiazolyl hydrazones were synthesized by one pot reaction of thiophene-2-carbaldehyde or 2, 4-dichlorobenzaldehyde, thiosemicarbazide and various phenacyl bromides which were preliminarily screened for in vitro antioxidant and antifungal activities. Excellent DPPH and H 2 O 2 radical scavenged antioxidant activities were observed with almost all the tested compounds. Compounds 4a, 4b, 4c, 4e, 4f and 4i showed comparable DPPH scavenged antioxidant potential (90.26-96.56%) whereas H 2 O 2 scavenged antioxidant activity (90.98-92.08%) was noticeable in case of 4a and 4f; showing significant antioxidant potential comparable with the standard ascorbic acid (95.3%). In vitro antifungal activity of synthesized compounds against fungal species Candida albicance, Aspergillus niger and Aspergillus flavus was found to be moderate to good as compared with the standard fluconazole and MIC values were found in the range of 3.12-25μg/mL. Molecular docking studies revealed that the compounds 4a, 4b and 4c have a potential to become lead molecules in drug discovery process. In silico ADMET study was also performed for predicting pharmacokinetic and toxicity profile of the synthesized antioxidants which expressed good oral drug like behaviour and non-toxic nature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Screening for antifungal activities of extracts of the brazilian seaweed genus Laurencia (Ceramiales, Rhodophyta

    Directory of Open Access Journals (Sweden)

    Erika M. Stein

    2011-04-01

    Full Text Available The resistance of pathogens to commonly used antibiotics has enhanced morbidity and mortality and has triggered the search for new drugs. Several species of the red alga genus Laurencia are very interesting candidates as potential sources of natural products with pharmaceutical activity because they are known to produce a wide range of chemically interesting halogenated secondary metabolites. This is an initial report of the antifungal activities of the secondary metabolites of five species of Laurencia, collected in the state of Espírito Santo, against three strains of pathogenic fungi: Candida albicans (CA, Candida parapsilosis (CP, and Cryptococcus neoformans (CN. Minimum inhibitory concentrations (MIC of the algal extracts were determined by serial dilution method in RPMI 1640 Medium in 96-well plates according to the NCCLS and microbial growth was determined by absorbance at 492nm. A result showing maintenance or reduction of the inoculum was defined as fungistatic, while fungicidal action was no observed growth in the 10 µL fungistatic samples subcultured in Sabouraud Agar. Our results indicate that apolar extracts of Laurencia species possess antifungal properties and encourage continued research to find new drugs for therapy of infectious diseases in these algae.

  5. Antifungal activity of the aqueous extract of Ilex paraguariensis against Malassezia furfur.

    Science.gov (United States)

    Filip, Rosana; Davicino, Roberto; Anesini, Claudia

    2010-05-01

    Malassezia furfur is a lipodependent, dimorphic and saprophyte fungus which causes pityriasis versicolor, dandruff and seborrheic dermatitis in humans. The drugs available to treat this fungal infection are few. These drugs are highly toxic and are costly when used in prolonged treatments. For these reasons, it is necessary to find new compounds to treat these infections. Ilex paraguariensis St Hilaire is a plant that grows in Argentina, Brazil and Paraguay. The aim of this study was to evaluate the effect of the aqueous extract of Ilex paraguariensis on the growth of M. furfur. High performance liquid chromatography (HPLC) was employed to identify and isolate compounds of I. paraguariensis and the agar-well diffusion method was used to assess the antifungal activity of the extract. The fungicidal/fungistatic effect was evaluated by the modified Thompson assay. The results demonstrated that the aqueous extract of Ilex paraguariensis (1000 mg/ml) possesses inhibitory activity against M. furfur. This antimalassezial activity was equivalent to 2.7 microg/ml of ketoconazole. Therefore, the topical use of Ilex paraguariensis extract as alternative antifungal agent can be suggested. Copyright (c) 2009 John Wiley & Sons, Ltd.

  6. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

    Science.gov (United States)

    Aljaeid, Bader Mubarak; Hosny, Khaled Mohamed

    2016-01-01

    Background and objective Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. Methods MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. Results The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. Conclusion MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. PMID:26869787

  7. Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

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    Welligton M. Santussi

    2017-06-01

    Full Text Available Antimicrobial peptides (AMPs are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv, its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus was evaluated by quantitative microplate reader assay. Tsv (100 and 500 μg/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 μg/well, which correspond to 30 and 75 μg/mL, respectively, of total soluble protein and Ts1 (1.5, 3, and 6 μg/well, which correspond to 2.18, 4.36, and 8.72 μM, respectively showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 μg/well (4.36 μM. The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 μM. The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first

  8. Microwave-Assisted Synthesis of Some 1,3,4-Oxadiazole Derivatives and Evaluation of Their Antibacterial and Antifungal Activity

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    Deepak Swarnkar

    2014-01-01

    Full Text Available A series of substituted 1,3,4-oxadiazole derivatives (3a–f and (6a–f have been synthesized from diphenylacetic acid hydrazide under microwave irradiation in various reaction conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, and 1H NMR. These targeted compounds have been tested for their antibacterial and antifungal activities compared to ampicillin and griseofulvin as standard drug. Compounds 3a, 3e, 3f, 6c, 6d, 6e, and 6d exhibited the maximum antibacterial activities while 3b, 3c, 3d, 3e, 6a, 6d, and 6e exhibited the maximum antifungal activities.

  9. Analysis of the in vitro activity of human neutrophils against Aspergillus fumigatus in presence of antifungal and immunosuppressive agents.

    Science.gov (United States)

    Decker, Christina; Wurster, Sebastian; Lazariotou, Maria; Hellmann, Anna-Maria; Einsele, Hermann; Ullmann, Andrew J; Löffler, Jürgen

    2017-10-09

    Neutrophils are essential in the first line defense against moulds. This in vitro study assessed different neutrophil effector mechanisms in the presence of clinically relevant antifungal and immunosuppressive agents. Therapeutic concentrations of liposomal amphotericin B led to reduced IL-8 and oxidative burst response to the synthetic stimulus PMA, whereas no major alterations of oxidative burst, phagocytosis, or cytokine response to germinated stages of Aspergillus fumigatus and no supra-additive effects of antifungal and immunosuppressive drugs were observed. Conventional and liposomal amphotericin B as well as voriconazole, however, led to reduced neutrophil extracellular trap formation in response to A. fumigatus germ tubes. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. The antifungal, cytotoxic, antitermite and insecticidal activities of Zizyphus jujube.

    Science.gov (United States)

    Ahmad, Bashir; Khan, Ibrar; Bashir, Shumaila; Azam, Sadiq; Ali, Niaz

    2011-10-01

    Plants are very useful, self-generating machines, producing a variety of useful bioactive products. Keeping in view this idea, the crude methanolic extract and various fractions of Zizyphus jujuba were screened for antifungal, cytotoxic, antitermite and insecticidal activities. Low activity was shown by the crude methanolic extract (12%), n-hexane (9%), chloroform (20%) and ethyl acetate (14%) fraction against Penicillium notatum. Low activity was shown by the n-hexane fraction against Aspergillus niger (10%) and Trichoderma harzianum (13%) and inactive against Aspergillus flavus, Fusarium oxysporum and Rhizopus stolonifer. The CHCl(3) fraction exhibited low activity of 10% against F. oxysporum while showing no activity against the rest of the test fungi. All the test samples were inactive against Rhizopus stolonifer. The crude methanolic extract was highly cytotoxic (73.33%) at the concentration of 1000 (µg/ml) while the rest of the test samples were low in toxicity at the same concentration. The crude methanolic extract of Zizyphus jujuba showed significant antitermite activity against Heterotermes indicola, among the test samples. Against Tribolium castaneum, Rhizopertha dominica and Callosbruchus analis the insecticidal activity was determined. All the test samples except n-hexane showed low activity (20%) against T. castaneum. The n-hexane fraction showed low activity (20%) against R. dominica while the rest of the fractions were inactive against it. Low activity of 40% and 20% was shown by the chloroform and n-hexane fraction respectively against C. analis. The results of the present study revealed that the plant could be as potent source of cytotoxic drugs.

  11. Mechanisms of Candida biofilm drug resistance

    Science.gov (United States)

    Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

    2013-01-01

    Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

  12. Interference of Plectranthus amboinicus (Lour. Spreng essential oil on the anti-Candida activity of some clinically used antifungals

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    Rinalda de Araújo G. de Oliveira

    Full Text Available Plants with medicinal properties have been applied for a long in the traditional health care, so that sometimes their use takes place concomitantly to the use of industrialized drugs. The aim of this study was to evaluate the interference of Plectranthus amboinicus essential oil on the anti-Candida activity of some clinically used antifungals by the solid medium diffusion procedure. Assayed antifungals were amphotericin B (100 µg/mL, ketoconazole (50 µg/mL and itraconazole (50 µg/mL. C. albicans, C. tropicalis, C. guilliermondii, C. krusei and C. stellatoidea were used as test microorganisms. P. amboinicus essential oil showed MIC value for most assayed yeast strains. The essential oil when assayed in its MIC value showed some interference on the anti-Candida effectiveness of the assayed antifungals. It was noted yeast growth inhibition zones with different diameters when the antifungals were tested alone and combined with the essential oil. P. amboinicus essential oil showed prominent interference on the anti-yeast activity of itraconazole providing a synergic effect on C. albicans, C. tropicalis, C. krusei and C. stellatoidea. Also, the essential oil interfered on the anti-yeast activity of ketoconazole when interacting with C. albicans, C. guilliermondii and C. stellatoidea providing, respectively, an antagonic and synergic effect. On the other hand, it was found a small interference on the anti-yeast effect of amphotericin B. These data showed that combined use of medicinal plants and/or derivatives with industrialized drugs, particularly antimicrobials, could interfere on their expected therapeutic effects.

  13. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

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    Aljaeid BM

    2016-01-01

    Full Text Available Bader Mubarak Aljaeid,1 Khaled Mohamed Hosny1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt Background and objective: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL; as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. Methods: MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. Results: The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. Conclusion: MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. Keywords: miconazole, Precirol ATO5, solid lipid nanoparticles, encapsulation, Cremophor RH40, antifungal activity

  14. Species distribution and antifungal susceptibility of Candida spp. isolated from superficial candidiasis in outpatients in Iran.

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    Razzaghi-Abyaneh, M; Sadeghi, G; Zeinali, E; Alirezaee, M; Shams-Ghahfarokhi, M; Amani, A; Mirahmadi, R; Tolouei, R

    2014-06-01

    Candidiasis is the most prevalent fungal infection affecting human and animals all over the world. This study represents the epidemiological aspects of superficial candidiasis in outpatients and in vitro antifungal susceptibility of etiologic Candida species. Clinical samples were taken from 173 patients including skin and nail scrapings (107; 61.8%), vaginal discharge (28; 16.2%), sputum (20; 11.6%), oral swabs (7; 4.0%), bronchoalveolar lavage (6; 3.5%) and 1 specimen (0.6%) of each eye tumor, gastric juice, urine, biopsy and urinary catheter and confirmed as candidiasis by direct microscopy, culture and histopathology. Susceptibility patterns of the isolated Candida species were determined using the disk diffusion and broth microdilution methods. Among 173 Candida isolates, C. albicans (72.3%) was the most prevalent species followed by C. parapsilosis (11.5%). Other identified species were C. glabrata, C. krusei, C. tropicalis, C. guilliermondii, C. intermedia and C. sake. Majority of the Candida isolates were susceptible to fluconazole (95.4%) followed by 5-flucytosine (89.6%), voriconazole (78.6%) itraconazole (48.0%) and ketoconazole (42.8%). Caspofungin was the most potent antifungal drug against C. albicans (MICs; 0.062-1 μg/mL), ketoconazole for C. parapsilosis and C. tropicalis (MICs; 0.031-0.25 μg/mL) and itraconazole for C. krusei, C. glabrata and C. guilliermondii (MICs; 0.031-1 μg/mL). This study reinforces the significance of superficial candidiasis as an important fungal infection with multiple clinical presentations. Our results further indicate that susceptibility testing to commonly used antifungals is crucial in order to select the appropriate therapeutic strategies which minimize complications while improving patients' life. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Optimization of antifungal activity of Aeollanthus heliotropioides oliv essential oil and Time Kill Kinetic Assay.

    Science.gov (United States)

    Ngo Mback, M N L; Agnaniet, H; Nguimatsia, F; Jazet Dongmo, P-M; Hzounda Fokou, J-B; Bakarnga-Via, I; Fekam Boyom, F; Menut, C

    2016-09-01

    The limitations encountered in the management of fungal infections are due to the resistance, high toxicity, and overuse of conventional antifungal drugs. For bringing solutions, the antifungal activity of Aeollanthus heliotropioides essential oil will be evaluated and optimized. The aerial parts of A. heliotropioides were harvested and essential oil extracted by hydrodistillation. The chemical composition was determined using gas chromatography and gas chromatography coupled with mass spectrometry and nuclear magnetic resonance. The sensitivity of fungal strains was determined using broth microdilution method. The fungicidal parameters were checked by viability assay using methylene blue dye. The Fractional Inhibitory Concentration Index was determined according the two-dimensional checkboard methods. The efficiency of the simulated optimum concentrations confirmed experimentally on American type culture collection strains, through the Time Kill Kinetic Study. The yield of extraction of essential oil was 0.1%. The major compounds were linalool (38.5%), Z-α-farnesene (25.1%), 9-hexa-decen-1-ol (13.9%) saturated/unsaturated massoia and γ-lactones (4.5%). The MIC of extract on yeast isolates ranged from 0.6mg/mL to 5mg/mL. The combination of essential oil with thymol leads mainly to synergistic effects (0.5≤FICI). The optimums of essential oil (1.6±0.4μl/mL) and thymol (0.6±0.1mg/mL) revealed a total inhibition of yeast after 120 and 180minutes according to the yeasts strains used. This study highlights the in vitro antifungal activity of A. heliotropioides essential oil and it synergistic effect with thymol. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Antifungal susceptibility patterns of yeasts and filamentous fungi isolated from nail infection.

    Science.gov (United States)

    Ataides, F S; Chaul, M H; El Essal, F E; Costa, C R; Souza, L K H; Fernandes, O F L; Silva, M R R

    2012-12-01

    Onychomycosis is the nail infection caused by a wide spectrum of fungi species, including yeasts, dermatophytes and filamentous fungi non-dermatophytes (FFND). This fungal infection represents an important medical problem because it involves the patient's life quality. The aim was to isolate and identify the fungal agents of onychomycosis, and to determine the in vitro susceptibility to antifungal agents. During the period of March 2008 to March 2009, 114 patients clinically suspected of having onychomycosis were examined. Demographic data, mainly age and gender were obtained from each patient. The nail samples collected (136) were submitted to direct examination with potassium hydroxide 20% and grown on Sabouraud dextrose agar. The in vitro antifungal susceptibility testing was performed according to the method of broth microdilution, recommended by the Clinical Laboratory Standards Institute (CLSI). Onychomycosis was observed in 95 (83.3%) patients, including 16 men (16.8%) and 79 women (83.2%), with mean age of 48.1 years. Candida parapsilosis, Trichophyton rubrum and Fusarium spp were the fungi most frequently isolated. The most of the isolated yeasts showed susceptibility to antifungal agents studied. Among filamentous fungi, high MIC values to itraconazole were found for T. rubrum and T. mentagrophytes, while Fusarium spp showed decreased susceptibility to itraconazole and voriconazole. C. parapsilosis was the most common fungal species isolated from patients with onychomycosis. The different response obtained by in vitro susceptibility testing to drugs shows the importance of these methods to assist clinicians in choosing the best therapeutic option. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  17. Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology.

    Science.gov (United States)

    Morgan, Jessica E; Hassan, Hadeel; Cockle, Julia V; Lethaby, Christopher; James, Beki; Phillips, Robert S

    2017-01-01

    The incidence of invasive fungal disease (IFD) is rising, but its treatment in paediatric haematology and oncology patients is not yet standardised. This review aimed to critically appraise and analyse the clinical practice guidelines (CPGs) that are available for paediatric IFD. Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, the Guidelines International Network (GIN), guideline.gov and Google were performed and combined fungal disease (Fung* OR antifung*OR Candida* OR Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All guidelines were assessed using the AGREE II tool and recommendations relating to prophylaxis, empirical treatment and specific therapy were extracted. Nineteen guidelines met the inclusion criteria. The AGREE II scores for the rigour of development domain ranged from 11 to 92 % with a median of 53 % (interquartile range 32-69 %). Fluconazole was recommended as antifungal prophylaxis in all nine of the included guidelines which recommended a specific drug. Liposomal amphotericin B was recommended in all five guidelines giving empirical therapy recommendations. Specific therapy recommendations were given for oral or genital candidiasis, invasive candida infection, invasive aspergillosis and other mould infections. In many areas, recommendations were clear about appropriate practice but further clarity was required, particularly relating to the decision to discontinue empirical antifungal treatment, the relative benefits of empiric and pre-emptive strategies and risk stratification. Future CPGs could consider working to published guideline production methodologies and sharing summaries of evidence appraisal to reduce duplication of effort, improving the quality and efficiency of CPGs in this area.

  18. Mapping and Identification of Antifungal Peptides in the Putative Antifungal Protein AfpB from the Filamentous Fungus Penicillium digitatum.

    Science.gov (United States)

    Garrigues, Sandra; Gandía, Mónica; Borics, Attila; Marx, Florentine; Manzanares, Paloma; Marcos, Jose F

    2017-01-01

    Antifungal proteins (AFPs) from Ascomycetes are small cysteine-rich proteins that are abundantly secreted and show antifungal activity against non-producer fungi. A gene coding for a class B AFP (AfpB) was previously identified in the genome of the plant pathogen Penicillium digitatum . However, previous attempts to detect the AfpB protein were not successful despite the high expression of the corresponding afpB gene. In this work, the structure of the putative AfpB was modeled. Based on this model, four synthetic cysteine-containing peptides, PAF109, PAF112, PAF118, and PAF119, were designed and their antimicrobial activity was tested and characterized. PAF109 that corresponds to the γ-core motif present in defensin-like antimicrobial proteins did not show antimicrobial activity. On the contrary, PAF112 and PAF118, which are cationic peptides derived from two surface-exposed loops in AfpB, showed moderate antifungal activity against P. digitatum and other filamentous fungi. It was also confirmed that cyclization through a disulfide bridge prevented peptide degradation. PAF116, which is a peptide analogous to PAF112 but derived from the Penicillium chrysogenum antifungal protein PAF, showed activity against P. digitatum similar to PAF112, but was less active than the native PAF protein. The two AfpB-derived antifungal peptides PAF112 and PAF118 showed positive synergistic interaction when combined against P. digitatum . Furthermore, the synthetic hexapeptide PAF26 previously described in our laboratory also exhibited synergistic interaction with the peptides PAF112, PAF118, and PAF116, as well as with the PAF protein. This study is an important contribution to the mapping of antifungal motifs within the AfpB and other AFPs, and opens up new strategies for the rational design and application of antifungal peptides and proteins.

  19. Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole

    KAUST Repository

    Campos, Mônica C.

    2017-10-25

    Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 5–8 million people in Latin America. Although the nitroheterocyclic compound benznidazole has been the front-line drug for several decades, treatment failures are common. Benznidazole is a pro-drug and is bio-activated within the parasite by the mitochondrial nitroreductase TcNTR-1, leading to the generation of reactive metabolites that have trypanocidal activity. To better assess drug action and resistance, we sequenced the genomes of T. cruzi Y strain (35.5 Mb) and three benznidazole-resistant clones derived from a single drug-selected population. This revealed the genome-wide accumulation of mutations in the resistant parasites, in addition to variations in DNA copy-number. We observed mutations in DNA repair genes, linked with increased susceptibility to DNA alkylating and inter-strand cross-linking agents. Stop-codon-generating mutations in TcNTR-1 were associated with cross-resistance to other nitroheterocyclic drugs. Unexpectedly, the clones were also highly resistant to the ergosterol biosynthesis inhibitor posaconazole, a drug proposed for use against T. cruzi infections, in combination with benznidazole. Our findings therefore identify the highly mutagenic activity of benznidazole metabolites in T. cruzi, demonstrate that this can result in multi-drug resistance, and indicate that vigilance will be required if benznidazole is used in combination therapy.

  20. Dynamics of Mixed- Candida Species Biofilms in Response to Antifungals.

    Science.gov (United States)

    Vipulanandan, G; Herrera, M; Wiederhold, N P; Li, X; Mintz, J; Wickes, B L; Kadosh, D

    2018-01-01

    Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.

  1. Antifungal activity of essential oils against selected terverticillate penicillia.

    Science.gov (United States)

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis.

  2. Antifungal activity of essential oils against selected terverticillate penicillia

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    Soňa Felšöciová

    2015-02-01

    Full Text Available The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita, L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis.

  3. Potential antifungal activity of Cladonia aff. rappii A. Evans

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    Claudia M. Plaza

    2017-10-01

    Full Text Available Context: Lichen is a self-supporting symbiotic organism composed of a fungus and an algal partner. They have manifold biological activities like antiviral, antibiotic, antioxidant, antitumor, allergenic and inhibition of plant growth. Species of Cladonia, have been studied by its antifungal activity. Aims: To evaluate the antifungal activity determination of Cladonia aff. rappii against five yeasts, four of genus Candida and one Cryptococcus, using water, ethanol and dichloromethane extracts. Methods: The evaluation of the antifungal activity was developed by three diffusion methods such as spot-on-a-lawn, disc diffusion and well diffusion. Additionally, the values of minimal inhibitory concentration (MIC and the minimum fungicidal concentration (MFC were determined. Results: Based on the experimental results obtained, the best antifungal activity was using ethanol extract at 20 mg/mL against Candida albicans, applying the three diffusion methods above mentioned. With ethanol extract, the lower MIC was against Candida glabrata and the lower MFC were with Candida glabrata, C. krusei, C. parapsilosis and C. tropicalis. The dichloromethane extract presented the lowest MIC and MFC against C. neoformans. Not activity was observed with aqueous extract. Conclusions: The present study revealed antifungal and fungicidal activity in the extract of lichen Cladonia aff. rappii.

  4. Antifungal compounds from cultures of dairy propionibacteria type strains.

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    Lind, Helena; Sjögren, Jörgen; Gohil, Suresh; Kenne, Lennart; Schnürer, Johan; Broberg, Anders

    2007-06-01

    Antifungal compounds from cultures of five type strains of dairy propionibacteria, as well as from the cultivation medium, were studied. Cell-free supernatants and medium were fractionated by C(18) solid phase extraction. The aqueous 95% acetonitrile fractions were analyzed by GC-MS or subjected to reversed-phase HPLC, to identify, quantify or isolate antifungal substances. The resulting HPLC fractions were screened for antifungal activity against the mold Aspergillus fumigatus and the yeast Rhodotorula mucilaginosa. Active fractions were further separated by HPLC and the structures of the compounds were determined by spectroscopic and chromatographic methods. All five strains produced 3-phenyllactic acid, at concentrations ranging from 1.0 microg mL(-1) (Propionibacterium freudenreichii ssp. shermanii) to 15.1 microg mL(-1) (Propionibacterium thoenii), and at L/D -ratios ranging from 2 : 3 (Propionibacterium acidipropionici) to 9 : 1 (Propionibacterium freudenreichii). A number of active compounds found in cultures of propionibacteria were also present in noninoculated growth medium: two antifungal diketopiperazines, cyclo(L-Phe-L-Pro) and cyclo(L-Ile-L-Pro), and seven antifungal linear peptides. Three of the linear peptides corresponded to sequences found in the medium component casein, suggesting their origin from this component, whereas the diketopiperazines were suggested to be formed from medium peptides by heat treatment.

  5. Comparison of the Antifungal effect of Licorice Root, Althoca Officinalis Extracts and Ketoconazole on Malassezia Furfur

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    Y Motaharinia

    2011-12-01

    Conclusion: The present study showed that Althoca officinalis flower extract compared with the Althoca officinalis root and licorice root extracts have a higher antifungal effect. Also ketoconazole, compared with these extracts, have a high antifungal effect on Malassezia furfur.

  6. Antifungal activity of nicotine and its cobalt complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

  7. Antifungal Applications of Ag-Decorated Hydroxyapatite Nanoparticles

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    C. A. Zamperini

    2013-01-01

    Full Text Available Pure hydroxyapatite (HA and hydroxyapatite decorated with silver (HA@Ag nanoparticles were synthesized and characterized. The antifungal effect of HA@Ag nanoparticles in a distilled water solution was evaluated against Candida albicans. The origin of the antifungal activity of the HA@Ag is also discussed. The results obtained showed that the HA nanorod morphology remained the same with Ag ions decorations on the HA structure which were deposited in the form of nanospheres. Interaction where occurred between the structure and its defect density variation in the interfacial HA@Ag and intrafacial HA region with the fungal medium resulted in antifungal activity. The reaction mechanisms involved oxygen and water adsorption which formed an active complex cluster. The decomposition and desorption of the final products as well as the electron/hole recombination process have an important role in fungicidal effects.

  8. Taxonomy and antifungal susceptibility of clinically important Rasamsonia species

    DEFF Research Database (Denmark)

    Houbraken, J.; Giraud, S.; Meijer, M.

    2013-01-01

    In recent years, Geosmithia argillacea has been increasingly reported in humans and animals and can be considered an emerging pathogen. The taxonomy of Geosmithia was recently studied, and Geosmithia argillacea and related species were transferred to the new genus Rasamsonia. The diversity among...... the presence of four species in the Rasamsonia argillacea complex, two of which are newly described here: R. piperina sp. nov. and R. aegroticola sp. nov. In contrast to other related genera, all Rasamsonia species can be identified with ITS sequences. A retrospective identification was performed on recently...... was the least active of the antifungals tested. The phenotypically similar species R. brevistipitata and R. cylindrospora had different antifungal susceptibility profiles, and this indicates that correct species identification is important to help guide appropriate antifungal therapy....

  9. Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.

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    Takahashi, Hidetoshi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

    2014-10-01

    Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm2 and 1 μg/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. © 2014 Japanese Dermatological Association.

  10. Isolation and antifungal screening of endophytic fungi from Erigeron canadensis

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    Xuelian Bai

    2017-07-01

    Full Text Available Sixteen fungal strains isolated from the Erigeron canadensis, one of traditional Chinese medicines used to treat the pathogenic infection and dysentery, were evaluated for their antifungal activities against one human pathogen Candida albicans, and two phytopathogens, Colletotrichum fructicola and Rhizoctonia cerealis. The bioassay results indicated that the ethyl acetate extract of the fermentation broth of these fungal endophytes had stronger antimicrobial activities. Among these endophytic strains, the ethyl acetate extracts of strains NPR003 and NPR005 showed the strongest inhibitory effects and has potential application in the discovery of new antifungal agents. This was the first report on the isolation of endophytic fungi from E. canadensis and evaluation of their antifungal activities.

  11. Antifungal Activity of Bacillus coagulans TQ33, Isolated from Skimmed Milk Powder, against Botrytis cinerea

    OpenAIRE

    Wang, Hai Kuan; Xiao, Rui Feng; Qi†, Wei

    2013-01-01

    Bacillus coagulans TQ33 is isolated from the skimmed milk powder and has a broad antifungal activity against pathogens such as Botrytis cinerea, Alternaria solani, Phytophthora drechsleri Tucker, Fusarium oxysporum and Glomerella cingulata. The characteristics of active antifungal substances produced by B. coagulans TQ33 and its antifungal effects against the growth of plant pathogenic fungi has been evaluated. The effect of pH, temperature and protease on the antifungal activity of B. coagul...

  12. In vitro drug susceptibility of two strains of the wildlife trypanosome, Trypanosoma copemani: A comparison with Trypanosoma cruzi.

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    Botero, Adriana; Keatley, Sarah; Peacock, Christopher; Thompson, R C Andrew

    2017-04-01

    Trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. Within Australia, several native Trypanosoma species have been described infecting wildlife. However, only Trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (Bettongia penicillata). The impact that some trypanosomes have on the health of the vertebrate host has led to the development of numerous drug compounds that could inhibit the growth or kill the parasite. This study investigated and compared the in vitro susceptibility of two strains of T. copemani (G1 and G2) and one strain of Trypanosoma cruzi (10R26) against drugs that are known to show trypanocidal activity (benznidazole, posaconazole, miltefosine and melarsoprol) and against four lead compounds, two fenarimols and two pyridine derivatives (EPL-BS1937, EPL-BS2391, EPL-BS0967, and EPL-BS1246), that have been developed primarily against T.cruzi. The in vitro cytotoxicity of all drugs against L6 rat myoblast cells was also assessed. Results showed that both strains of T. copemani were more susceptible to all drugs and lead compounds than T. cruzi, with all IC50 values in the low and sub-μM range for both species. Melarsoprol and miltefosine exhibited the highest drug activity against both T. copemani and T. cruzi, but they also showed the highest toxicity in L6 cells. Interestingly, both fenarimol and pyridine derivative compounds were more active against T. copemani and T. cruzi than the reference drugs benznidazole and posaconazole. T. copemani strains exhibited differences in susceptibility to all drugs demonstrating once again considerable differences in their biological behaviour. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Antifungal activity of terrestrial Streptomyces rochei strain HF391 against clinical azole -resistant Aspergillus fumigatus

    Science.gov (United States)

    Hadizadeh, S; Forootanfar, H; Shahidi Bonjar, GH; Falahati Nejad, M; Karamy Robati, A; Ayatollahi Mousavi, SA; Amirporrostami, S

    2015-01-01

    Background and Purpose: Actinomycetes have been discovered as source of antifungal compounds that are currently in clinical use. Invasive aspergillosis (IA) due to Aspergillus fumigatus has been identified as individual drug-resistant Aspergillus spp. to be an emerging pathogen opportunities a global scale. This paper described the antifungal activity of one terrestrial actinomycete against the clinically isolated azole-resistant A. fumigatus. Materials and Methods: Soil samples were collected from various locations of Kerman, Iran. Thereafter, the actinomycetes were isolated using starch-casein-nitrate-agar medium and the most efficient actinomycetes (capable of inhibiting A. fumigatus) were screened using agar block method. In the next step, the selected actinomycete was cultivated in starch-casein- broth medium and the inhibitory activity of the obtained culture broth was evaluated using agar well diffusion method. Results: The selected actinomycete, identified as Streptomyces rochei strain HF391, could suppress the growth of A. fumigatus isolates which was isolated from the clinical samples of patients treated with azoles. This strain showed higher inhibition zones on agar diffusion assay which was more than 15 mm. Conclusion: The obtained results of the present study introduced Streptomyces rochei strain HF391 as terrestrial actinomycete that can inhibit the growth of clinically isolated A. fumigatus. PMID:28680984

  14. Viable quantitative PCR for assessing the response of Candida albicans to antifungal treatment.

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    Agustí, Gemma; Fittipaldi, Mariana; Morató, Jordi; Codony, Francesc

    2013-01-01

    Propidium monoazide (PMA) or ethidium bromide monoazide (EMA) treatment has been used before nucleic acid detection methods, such as PCR, to distinguish between live and dead cells using membrane integrity as viability criterion. The performance of these DNA intercalating dyes was compared in many studies utilizing different microorganisms. These studies demonstrated that EMA and PMA differ in their abilities to identify nonviable cells from mixed cell populations, depending on the microorganism and the nature of the sample. Due to this heterogeneity, both dyes were used in the present study to specifically distinguish dead from live Candida albicans cells using viable quantitative PCR (qPCR). The viable qPCR was optimized, and the best results were obtained when pre-treating the cells for 10 min in the dark with 25 μM EMA followed by continuous photoactivation for 15 min. The suitability of this technique to distinguish clotrimazole- and fluconazole-treated C. albicans cells from untreated cells was then assessed. Furthermore, the antifungal properties of two commercial essential oils (Thymus vulgaris and Matricaria chamomilla) were evaluated. The viable qPCR method was determined to be a feasible technique for assessing the viability of C. albicans after drug treatment and may help to provide a rapid diagnostic and susceptibility testing method for fungal infections, especially for patients treated with antifungal therapies.

  15. Polymeric Nanofiber/Antifungal Formulations Using a Novel Co-extrusion Approach.

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    Mofidfar, Mohammad; Wang, Jia; Long, Lisa; Hager, Christopher L; Vareechon, Chairut; Pearlman, Eric; Baer, Eric; Ghannoum, Mahmoud; Wnek, Gary E

    2017-08-01

    We report the successful implementation of a novel melt co-extrusion process to fabricate ca. 1 μm diameter fibers of poly(caprolactone) (PCL) containing the antifungal compound clotrimazole in concentrations between 4 and 8 wt%. The process involves co-extrusion of a clotrimazole-loaded PCL along with poly(ethylene oxide) (PEO) as a co-feed, with subsequent removal of PEO to isolate PCL-clotrimazole fibers. In vitro tests of the clotrimazole-containing fibers against the fungus Aspergillus fumigatus, Candida albicans, and Trichophyton mentagrophytes strains demonstrated good antifungal activity which was maintained for more than 3 weeks. An in vivo study using a mouse model showed the lowest tissue fungal burden for PCL-clotrimazole when compared to a PCL-only patch and untreated controls. Comparative studies were conducted with clotrimazole-containing PCL fibers fabricated by electrospinning. Our data showed that the co-extruded, clotrimazole-containing fibers maintain activity for longer times vs. electrospun samples. This, coupled with the much higher throughput of the co-extrusion process vs. electrospinning, renders this new approach very attractive for the fabrication of drug-releasing polymer fibers.

  16. Chemical Composition, Antibacterial and Antifungal Activities of Crude Dittrichia viscosa (L. Greuter Leaf Extracts

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    Wafa Rhimi

    2017-06-01

    Full Text Available The small amount of data regarding the antifungal activity of Dittrichia viscosa (L. Greuter against dermatophytes, Malassezia spp. and Aspergillus spp., associated with the few comparative studies on the antimicrobial activity of methanolic, ethanolic, and butanolic extracts underpins the study herein presented. The total condensed tannin (TCT, phenol (TPC, flavonoid (TFC, and caffeoylquinic acid (CQC content of methanol, butanol, and ethanol (80% and 100% extracts of D. viscosa were assessed and their bactericidal and fungicidal activities were evaluated. The antibacterial, anti-Candida and anti-Malassezia activities were evaluated by using the disk diffusion method, whereas the anti-Microsporum canis and anti-Aspergillus fumigatus activities were assessed by studying the toxicity effect of the extracts on vegetative growth, sporulation and germination. The methanolic extract contained the highest TPC and CQC content. It contains several phytochemicals mainly caffeoylquinic acid derivatives as determined by liquid chromatography with photodiode array and electrospray ionisation mass spectrometric detection (LC/PDA/ESI-MS analysis. All extracts showed an excellent inhibitory effect against bacteria and Candida spp., whereas methanolic extract exhibited the highest antifungal activities against Malassezia spp., M. canis and A. fumigatus strains. The results clearly showed that all extracts, in particular the methanolic extract, might be excellent antimicrobial drugs for treating infections that are life threatening (i.e., Malassezia or infections that require mandatory treatments (i.e., M. canis or A. fumigatus.

  17. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives.

    Science.gov (United States)

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-( N , N -dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a-b) as well as chalcone derivatives (3a-c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans .

  18. Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer.

    Science.gov (United States)

    Griesser, Stefani S; Jasieniak, Marek; Coad, Bryan R; Griesser, Hans J

    2015-12-14

    Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (∼20 nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices.

  19. Nepenthes rafflesiana pitcher liquid has antifungal activity against Candida spp.

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    Hanna Yolanda

    2014-08-01

    Full Text Available Background To develop new effective antifungals, it is essential to search for antifungal compounds from plants such as Nepenthes spp., which have their greatest diversity in Indonesia. Since chitin-induced liquid (CIL from Nepenthes khasiana pitchers has antifungal activity, due to their naphthoquinone content, this study aimed to evaluate antifungal activity of Nepenthes rafflesiana pitcher liquids on Candida spp. Methods Collected pitcher liquids were of 3 types: non-induced liquid (NIL, prey-induced liquid (PIL, and chitin-induced liquid (CIL. Non-induced liquid (NIL was collected from fresh naturally opened pitchers, PIL from opened pitchers after 3 hours of induction with Zophobas morio larvae, and CIL from closed pitchers after 5 days of chitin solution injection. The antifungal activity of the liquids against C. albicans, C. glabrata, C. krusei, and C. tropicalis were detected by disc diffusion and macrodilution methods. Results Inhibition zone diameters of NIL, PIL, and CIL against C. albicans were 35.00 (35.00 – 39.33 mm, 26.33 (23.00 – 40.00 mm, and 30.00 ( 28.00 – 32.00 mm, respectively, while for C. glabrata the zone diameters were 22.22 ± 3.66 mm, 29.89 ± 2.79 mm, and 28.89 ± 1.17 mm, respectively. No inhibition zones were found for NIL, PIL, and CIL against C. krusei and C. tropicalis. At concentrations of 80%, almost all samples showed visually apparent inhibition of fungal growth. Conclusion The pitcher liquid of N. rafflesiana has antifungal properties, presumably due to the presence of many potentially active substances, such as naphthoquinones, as has been proven in other studies.

  20. Nepenthes rafflesiana pitcher liquid has antifungal activity against Candida spp.

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    Hanna Yolanda

    2015-12-01

    Full Text Available BACKGROUND To develop new effective antifungals, it is essential to search for antifungal compounds from plants such as Nepenthes spp., which have their greatest diversity in Indonesia. Since chitin-induced liquid (CIL from Nepenthes khasiana pitchers has antifungal activity, due to their naphthoquinone content, this study aimed to evaluate antifungal activity of Nepenthes rafflesiana pitcher liquids on Candida spp. METHODS Collected pitcher liquids were of 3 types: non-induced liquid (NIL, prey-induced liquid (PIL, and chitin-induced liquid (CIL. Non-induced liquid (NIL was collected from fresh naturally opened pitchers, PIL from opened pitchers after 3 hours of induction with Zophobas morio larvae, and CIL from closed pitchers after 5 days of chitin solution injection. The antifungal activity of the liquids against C. albicans, C. glabrata, C. krusei, and C. tropicalis were detected by disc diffusion and macrodilution methods. RESULTS Inhibition zone diameters of NIL, PIL, and CIL against C. albicans were 35.00 (35.00 – 39.33 mm, 26.33 (23.00 – 40.00 mm, and 30.00 ( 28.00 – 32.00 mm, respectively, while for C. glabrata the zone diameters were 22.22 ± 3.66 mm, 29.89 ± 2.79 mm, and 28.89 ± 1.17 mm, respectively. No inhibition zones were found for NIL, PIL, and CIL against C. krusei and C. tropicalis. At concentrations of 80%, almost all samples showed visually apparent inhibition of fungal growth. CONCLUSION The pitcher liquid of N. rafflesiana has antifungal properties, presumably due to the presence of many potentially active substances, such as naphthoquinones, as has been proven in other studies.

  1. Hydrogel of Ketoconazole and PAMAM Dendrimers: Formulation and Antifungal Activity

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    Elzbieta Tryniszewska

    2012-04-01

    Full Text Available Ketoconazole (KET, an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 and generation 3 on the solubility and antifungal activity of KET and to design and evaluate KET hydrogel with PAMAM dendrimers. It was shown that the surface charge of PAMAM dendrimers strongly affects their influence on the improvement of solubility and antifungal activity of KET. The MIC and MFC values obtained by broth dilution method indicate that PAMAM-NH2 dendrimers significantly (up to 16-fold increased the antifungal activity of KET against Candida strains (e.g., in culture Candida albicans 1103059/11 MIC value was 0.008 μg/mL and 0.064 μg/mL, and MFC was 2 μg/mL and 32 μg/mL for KET in 10 mg/mL solution of PAMAM-NH2 G2 and pure KET, respectively. Antifungal activity of designed KET hydrogel with PAMAM-NH2 dendrimers measured by the plate diffusion method was definitely higher than pure KET hydrogel and than commercial available product. It was shown that the improvement of solubility and in the consequence the higher KET release from hydrogels seems to be a very significant factor affecting antifungal activity of KET in hydrogels containing PAMAM dendrimers.

  2. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

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    Julia Breger

    2007-02-01

    Full Text Available There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2% that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.

  3. Antibacterial and Antifungal Potential of Himalayan Medicinal Plants for Treating Wound Infections

    International Nuclear Information System (INIS)

    Habiba, U.; Ahmad, M.; Shinwari, S.; Sultana, S.; Zafar, M.; Shinwari, Z. K.

    2016-01-01

    Many bacterial and fungal strains are involved in wound infectious diseases as most of these strains become resistant to the most commonly used synthetic drugs in Himalayan region. Plant based natural products seem to be an alternative to this problem. The aim of this investigation was to evaluate the In vitro antibacterial and antifungal activities of 30 medicinal plants used in folk recipes by Himalayan people to treat wound infections against multi-drug resistant pathogens. In total of six medically important Myco-bacterial strains Streptococcus pyogenes, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger were tested against methanolic plant extracts at 5 mg/ml concentration using agar disc well diffusion method to determined Minimum inhibitory concentrations (MICs). The plant extracts showed varied levels of MICs against test microorganisms. The strongest antibacterial activity was reported in methanolic extract of Cynadon dactylon (L.) Pers. against Klebsiella pneumoniae with 20.67±1.36 mm MICs, while Candida albicans was considered to be the most resistant pathogen with MICs 9.6±0.57 mm. The findings were compared with results obtained using standard antibiotics, aminooxanilic, ciprofloxacin, cefotaxime, fluconazole and itraconazole at conc. 5mg/ ml. The results provide an evidence of folk medicinal uses of plants among the Himalayan communities to treat wounds. Further research needs to be carried out to identify the active molecules and evaluate the in vivo antibacterial and antifungal activities as well as toxicity level with clinical trials to use full potential of these plants for drug discovery development to control wounds globally. (author)

  4. Epidemiology and antifungal susceptibility of Candida species in a tertiary care hospital, Kolkata, India

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    Partha Bhattacharjee

    2016-06-01

    Conclusion: Species-level identification of Candida and their antifungal sensitivity testing should to be performed to achieve better clinical result and to select an appropriate and effective antifungal therapy. High resistance to antifungal agents is an alarming sign to the healthcare professionals.

  5. In vitro antifungal activities of 26 plant extracts on mycelial growth of ...

    African Journals Online (AJOL)

    Antifungal activities of 26 plant extracts were tested against Phytophthora infestans using radial growth technique. While all tested plant extracts produced some antifungal activities Xanthium strumarium, Lauris nobilis, Salvia officinalis and Styrax officinalis were the most active plants that showed potent antifungal activity.

  6. Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview.

    Science.gov (United States)

    Goldani, Luciano Z; Wirth, Fernanda

    2017-08-01

    Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.

  7. Atmospheric pressure cold plasma as an antifungal therapy

    International Nuclear Information System (INIS)

    Sun Peng; Wu Haiyan; Sun Yi; Liu Wei; Li Ruoyu; Zhu Weidong; Lopez, Jose L.; Zhang Jue; Fang Jing

    2011-01-01

    A microhollow cathode based, direct-current, atmospheric pressure, He/O 2 (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

  8. Comparison of Quantitative Antifungal Testing Methods for Textile Fabrics.

    Science.gov (United States)

    Imoto, Yasuo; Seino, Satoshi; Nakagawa, Takashi; Yamamoto, Takao A

    2017-01-01

     Quantitative antifungal testing methods for textile fabrics under growth-supportive conditions were studied. Fungal growth activities on unfinished textile fabrics and textile fabrics modified with Ag nanoparticles were investigated using the colony counting method and the luminescence method. Morphological changes of the fungi during incubation were investigated by microscopic observation. Comparison of the results indicated that the fungal growth activity values obtained with the colony counting method depended on the morphological state of the fungi on textile fabrics, whereas those obtained with the luminescence method did not. Our findings indicated that unique characteristics of each testing method must be taken into account for the proper evaluation of antifungal activity.

  9. Plant antifungal proteins and their applications in agriculture.

    Science.gov (United States)

    Yan, Juan; Yuan, Su-Su; Jiang, Luan-Luan; Ye, Xiu-Juan; Ng, Tzi Bun; Wu, Zu-Jian

    2015-06-01

    Fungi are far more complex organisms than viruses or bacteria and can develop numerous diseases in plants that cause loss of a substantial portion of the crop every year. Plants have developed various mechanisms to defend themselves against these fungi which include the production of low-molecular-weight secondary metabolites and proteins and peptides with antifungal activity. In this review, families of plant antifungal proteins (AFPs) including defensins, lectins, and several others will be summarized. Moreover, the application of AFPs in agriculture will also be analyzed.

  10. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    Energy Technology Data Exchange (ETDEWEB)

    Meneses, Erick A.; Durango, Diego L.; Garcia, Carlos M. [Universidad Nacional de Colombia, Medellin (Colombia). Facultad de Ciencias. Escuela de Quimica], e-mail: cmgarcia@unal.edu.co

    2009-07-01

    The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions. (author)

  11. Comparison of micafungin and voriconazole as empirical antifungal therapies in febrile neutropenic patients with hematological disorders: a randomized controlled trial.

    Science.gov (United States)

    Oyake, Tatsuo; Kowata, Shugo; Murai, Kazunori; Ito, Shigeki; Akagi, Tomoaki; Kubo, Kohmei; Sawada, Kenichi; Ishida, Yoji

    2016-06-01

    In cases of hematological malignancy, patients with persistent fever and neutropenia receive antifungal empirical therapy to prevent and treat invasive fungal infections. The clinical efficacy and safety of micafungin and voriconazole were compared. In this randomized, cooperative group, open-label trial, we assessed and compared the efficacy and safety of micafungin and voriconazole as an empirical antifungal therapy in febrile neutropenic patients with hematological malignancy. Patients were classified according to invasive fungal infection risk. There were no significant differences in clinical efficacy between the two treatments, evaluated based on (i) successful treatment of baseline fungal infection (no evaluation), (ii) absence of breakthrough fungal infection (P = 0.106), (iii) survival for ≥7 days after study completion (P = 0.335), (iv) premature study discontinuation due to poor efficacy (P = 0.424), and (v) resolution of fever during neutropenia (P = 0.756). Discontinuation due to drug-related adverse events (grades 3-4) occurred less frequently in the micafungin group (P = 0.005). The clinical efficacy did not differ between micafungin and voriconazole. Micafungin was generally better tolerated than voriconazole when given as an empirical antifungal therapy in patients with persistent fever and neutropenia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Antifungal activity of Coriandrum sativum essential oil, its mode of action against Candida species and potential synergism with amphotericin B.

    Science.gov (United States)

    Silva, Filomena; Ferreira, Susana; Duarte, Andreia; Mendonça, Dina I; Domingues, Fernanda C

    2011-12-15

    The increasing incidence of drug-resistant pathogens and toxicity of existing antifungal compounds has drawn attention towards the antimicrobial activity of natural products. The aim of the present study was to evaluate the antifungal activity of coriander essential oil according to classical bacteriological techniques, as well as with flow cytometry. The effect of the essential oil upon germ tube formation, seen as an important virulence factor, and potential synergism with amphotericin B were also studied. Coriander essential oil has a fungicidal activity against the Candida strains tested with MLC values equal to the MIC value and ranging from 0.05 to 0.4% (v/v). Flow cytometric evaluation of BOX, PI and DRAQ5 staining indicates that the fungicidal effect is a result of cytoplasmic membrane damage and subsequent leakage of intracellular components such as DNA. Also, concentrations bellow the MIC value caused a marked reduction in the percentage of germ tube formation for C. albicans strains. A synergetic effect between coriander oil and amphotericin B was also obtained for C. albicans strains, while for C. tropicalis strain only an additive effect was observed. This study describes the antifungal activity of coriander essential oil on Candida spp., which could be useful in designing new formulations for candidosis treatment. Copyright © 2011 Elsevier GmbH. All rights reserved.

  13. Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

    Science.gov (United States)

    Scorzoni, Liliana; de Lucas, Maria Pilar; Mesa-Arango, Ana Cecilia; Fusco-Almeida, Ana Marisa; Lozano, Encarnación; Cuenca-Estrella, Manuel; Mendes-Giannini, Maria Jose; Zaragoza, Oscar

    2013-01-01

    The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2–5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei. PMID:23555877

  14. Combination antifungal therapy for cryptococcal meningitis.

    Science.gov (United States)

    Day, Jeremy N; Chau, Tran T H; Wolbers, Marcel; Mai, Pham P; Dung, Nguyen T; Mai, Nguyen H; Phu, Nguyen H; Nghia, Ho D; Phong, Nguyen D; Thai, Cao Q; Thai, Le H; Chuong, Ly V; Sinh, Dinh X; Duong, Van A; Hoang, Thu N; Diep, Pham T; Campbell, James I; Sieu, Tran P M; Baker, Stephen G; Chau, Nguyen V V; Hien, Tran T; Lalloo, David G; Farrar, Jeremy J

    2013-04-04

    Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units [CFU] per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients

  15. Speciation and antifungal susceptibility of esophageal candidiasis in cancer patients in a tertiary care hospital in South India

    Directory of Open Access Journals (Sweden)

    J. Abirami Lakshmy

    2016-01-01

    Full Text Available Esophageal candidiasis is the most common opportunistic infection in patients with altered immunity such as Human Immunodeficiency Virus (HIV infection, cancer patients on chemotherapy and radiotherapy. Neutropenia, irradiation and chemotherapy will facilitate deeper mucosal invasion leading to esophageal candidiasis. Empirical treatment of esophageal candidiasis without antifungal susceptibility testing will lead to the emergence of drug resistant species increasing the morbidity and mortality associated with cancer. The present study aimed to study the frequency of esophageal candida in individuals with cancer, species level identification and antifungal susceptibility pattern. Scrapings of whitish appearing lesions were obtained from a total of thirty five cases of endoscopically identified esophageal candidiasis were obtained from cancer patients. Identification of the Candida isolates were done by cultivation in Sabouraud dextrose agar (SDA, Gram staining, germ tube test, colony morphology in Chrom agar and corn meal agar, sugar assimilation and fermentation tests. Antifungal susceptibility was done by Microbroth dilution method for Fluconazole, Itraconazole and Amphotericin B. We found that Candida albicans was the predominant species isolated followed by Candida tropicalis and Candida glabrata. Sensitivity rates were 94%, 96% and 100% for Fluconazole, Itraconazole and Amphotericin B. Species level identification of Candida isolated from esophageal candidiasis and their antifungal sensitivity testing should be performed for early identification of resistant strains and for promptly treating the cases there by preventing the dissemination of infection in case of immune-compromised individuals. Further the susceptibility pattern will facilitate therapeutic guidance especially in individuals prone to relapse. [J Med Allied Sci 2016; 6(1: 29-34

  16. Antifungal photosensitive activity of Porophyllum obscurum (Spreng.) DC.: Correlation of the chemical composition of the hexane extract with the bioactivity.

    Science.gov (United States)

    Postigo, Agustina; Funes, Matías; Petenatti, Elisa; Bottai, Hebe; Pacciaroni, Adriana; Sortino, Maximiliano

    2017-12-01

    We report Porophyllum obscurum as a source of new photosensitizers with potential use in Photodynamic Therapy as an alternative for oropharyngeal candidiasis treatment. The antifungal photosensitive activity of different extracts from P. obscurum was evaluated by using microdilution and bioautographic assays. The Minimum Fungicidal Concentration for hexanic extract under UV-A irradiation was 0.98μg/mL, but it was inactive in experiments without irradiation. The bioassay-guided fractionation of this extract led to the isolation of four thiophenes responsible for the photosensitive activity: 2,2':5'2″terthiophene, 5-(3-buten-1-ynyl)-2,2'-bithiophene, 5-(4-acetoxy-1-butenyl)-2,2'- bithiophene and 5-(4-hydroxy-1-butenyl)-2,2'- bithiophene, with Minimum Fungicidal Concentrations ranging 0.24-7.81μg/mL under UV-A irradiation. The activity of the hexanic extract was evaluated against 25 clinical strains of Candida spp. isolates as etiological agents of oropharyngeal candidiasis. No differences in susceptibility were observed in strains resistant and susceptible to conventional antifungal drugs. Qualitative and quantitative chemical analyses of seven samples of P. obscurum collected in four different phenological stages were carried out showing that full flowering stage possesses the highest thiophenes content. These data also allowed us to establish a correlation between the thiophene composition of the different extracts and their antifungal photosensitive activity, according to a second order polynomial model with the equation: y=11.2603-0.6831*x+0.0108*x 2 . The thiophenes isolated were the responsible of antifungal photosensitive activity and can be used for the future standardization of the extract. Results showed that P. obscurum hexanic extract could be potentially developed as an Herbal Medicinal Product to be applied as a photosensitizer in Photodynamic Therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Mapping and Identification of Antifungal Peptides in the Putative Antifungal Protein AfpB from the Filamentous Fungus Penicillium digitatum

    OpenAIRE

    Garrigues, Sandra; Gandía Gómez, Mónica; Borics, Attila; Marx, Florentine; Manzanares, Paloma; Marcos López, José Francisco

    2017-01-01

    Antifungal proteins (AFPs) from Ascomycetes are small cysteine-rich proteins that are abundantly secreted and show antifungal activity against non-producer fungi. A gene coding for a class B AFP (AfpB) was previously identified in the genome of the plant pathogen Penicillium digitatum. However, previous attempts to detect the AfpB protein were not successful despite the high expression of the corresponding afpB gene. In this work, the structure of the putative AfpB was modeled. Based on this ...

  18. Antifungal effect of Polar and non polar extracts of Aframomum ...

    African Journals Online (AJOL)

    The phytochemical screening revealed the presence of the following phytochemicals in different quantities; Alkaloids, Terpenoids, Anthraquinones, Flavonoids Tanins, Saponins. Results obtained showed that all the extracts had a significantly higher antifungal effect (p< 0.05) than the broad spectrum fungicide, Mancozeb at ...

  19. Antifungal Activity of Hypericum havvae Against Some Medical ...

    African Journals Online (AJOL)

    ... potency against Candida albicans and Cryptococcus laurentii, with the same MIC value of 1.56 mg/ml. Conclusion: Our findings support the use of Hypericum havvae in traditional medicine for the treatment of fungal infections, especially Candidiasis. Keywords: Antifungal activity, Candida, Hypericum havvae, Candidiasis ...

  20. Chemical composition and antifungal activity of essential oils of ...

    African Journals Online (AJOL)

    The aim of this study was to determine the chemical composition of the essential oils of Algerian citrus. They were extracted by hydrodistillation from the leaves of citrus species (orange, Bigaradier, mandarin and lemon), using gas chromatography/mass spectrometry (GC/MS). Their chemical composition and antifungal ...

  1. Tolerance of yeast biofilm cells towards systemic antifungals

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth

    of this thesis has been to explore the tolerance mechanisms of yeast biofilms to systemic antifungal agents and to identify the molecular target of a novel peptidomimetic with anti-biofilm activity. The genetic tractable S. cerevisiae was used as biofilm model system for the pathogenic Candida species...

  2. In vitro antifungal and cytotoxicity activities of selected Tanzanian ...

    African Journals Online (AJOL)

    Abstract. Purpose: To evaluate the antifungal and cytotoxic activities of four medicinal plants from Tanzania, namely, Mystroxylon aethiopicum ... The importance of medicinal plants in solving the healthcare problems of the world is gaining ... often with indefinite biological effects [3]. Medicinal plants therefore, have been ...

  3. Essential oil of Algerian Eucalyptus citriodora: Chemical composition, antifungal activity.

    Science.gov (United States)

    Tolba, H; Moghrani, H; Benelmouffok, A; Kellou, D; Maachi, R

    2015-12-01

    Essential oil of Eucalyptus citriodora is a natural product which has been attributed for various medicinal uses. In the present investigation, E. citriodora essential oil was used to evaluate its antifungal effect against medically important dermatophytes. Essential oil from the Algerian E. citriodora leaves was analyzed by GC and GC/MS. The antifungal effect of E. citriodora essential oil was evaluated against four dermatophytes: Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum using disc diffusion method, disc volatilization method, and agar dilution method. The chemical composition of the oil revealed the presence of 22 compounds accounting for 95.27% of the oil. The dominant compounds were citronellal (69.77%), citronellol (10.63%) and isopulegol (4.66%). The disc diffusion method, MIC and MFC determination, indicated that E. citriodora essential oil had a higher antifungal potential against the tested strains with inhibition zone diameter which varied from (12 to 90mm) and MIC and MFC values ranged from (0.6 to 5μL/mL and 1.25 to 5μL/mL) respectively. The M. gypseum was the most resistant to the oil. The results of the present study indicated that E. citriodora essential oil may be used as a new antifungal agent recommended by the pharmaceutical industries. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. In vitro Antifungal, Antioxidant and Cytotoxic Activities of a Partially ...

    African Journals Online (AJOL)

    higher antifungal activity on Candida albicans than on Aspergillus fumigatus. AMP III fraction showed greater in vitro antioxidant activity than the aqueous extract. SDS-PAGE analyses revealed the presence of two protein bands with molecular weight approximately of 16 and 67 KDa in AMP III. Protein concentration was 240 ...

  5. SHORT COMMUNICATION ANTI-FUNGAL ACTIVITIES OF m ...

    African Journals Online (AJOL)

    a

    of these metals complexes as food preservatives may only be fungi-static and not fungi-toxic, their use in bread preparation might extend the shelf life of bread from 24 hours to 96 hours. KEY WORDS: Anti-fungal activities, Alkali metal iodobenzoates, Alkaline earth metal iodobenzoates, m-Iodobenzoic acid, Bread mucor.

  6. Insecticidal, brine shrimp cytotoxicity, antifungal and nitric oxide free ...

    African Journals Online (AJOL)

    The crude methanolic extract and various fractions derived from the aerial parts of Myrsine africana were screened in vitro for possible insecticidal, antifungal, brine shrimp lethality and nitric oxide free radical scavenging activities. Low insecticidal activity (20 %) was shown by chloroform (CHCl3) and aqueous fractions ...

  7. Antiradical potential and antifungal activities of essential oils of the ...

    African Journals Online (AJOL)

    Investigations were conducted to determine the chemical composition, antiradical and antifungal activities of the essential oil extracted from the fresh leaves of Citrus latifolia var. Tahiti from Cameroon against Phaeoramularia angolensis. The essential oil obtained by hydrodistillation was analysed by GC and GC/MS.

  8. Evaluation of the antifungal properties of nystatin-salicylic acid ...

    African Journals Online (AJOL)

    The in vitro antifungal activity of nystatin-salicylic acid combinations against clinical isolates of Candida albicans was investigated separately using the overlay inoculum susceptibility disc, the decimal assay for additively (DDA) and the rate of time kill methods. The minimum inhibitory concentrations (MIC) of the individual ...

  9. Antifungal activity of rice straw extract on some phytopathogenic fungi

    African Journals Online (AJOL)

    user

    2012-09-04

    Sep 4, 2012 ... Key words: Rice straw, allelochemicals, antifungal, Aspergillus flavus, Alternaria alternata, Botrytis cinerea, amylase, protease ..... Identification and quantification of compounds in a series of allelopathic and non- allelopathic rice root exudates. J. Chem. Ecol. 30:1647-1662. Timmer LW, Peever TL, Solel Z, ...

  10. Antifungal activity of steroidal glycosides from Yucca gloriosa L.

    Science.gov (United States)

    Favel, A; Kemertelidze, E; Benidze, M; Fallague, K; Regli, P

    2005-02-01

    The antifungal activity of a crude steroidal glycoside extract from Yucca gloriosa flowers, named alexin, was investigated in vitro against a panel of human pathogenic fungi, yeasts as well as dermatophytes and filamentous species. The minimal inhibitory concentration (MIC) was determined by an agar dilution method. Alexin had a broad spectrum of antifungal activity, found to reside entirely in the spirostanoid fraction. The major tigogenyl glycosides, yuccaloeside B and yuccaloeside C, exhibited MICs between 0.39 and 6.25 microg[sol ]mL for all the tested yeast strains except for two (C. lusitaniae and C. kefyr). They were also active against several clinical Candida isolates known to be resistant to the usual antifungal agents. The MICs for the dermatophytes were between 0.78 and 12.5 microg[sol ]mL. The most sensitive filamentous species was A. fumigatus (MIC = 1.56 microg[sol ]mL). For most of the strains, the MICs of both glycosides were similar to those of the reference antifungal agent. Copyright 2005 John Wiley & Sons, Ltd.

  11. In vitro Antifungal Activity of Baccharis trimera Less (DC) Essential ...

    African Journals Online (AJOL)

    Purpose: To identify the main components of the essential oil (EO) of Baccharis trimera Less and investigate their in vitro antifungal activity against seven fungal strains that cause onychomycosis. Methods: The chemical composition of EO was determined using gas chromatography, and its minimum inhibitory concentration ...

  12. Antifungal activity of epithelial secretions from selected frog species ...

    African Journals Online (AJOL)

    This study aimed to investigate the antifungal activity of skin secretions from selected frogs (Amietia fuscigula, Strongylopus grayi and Xenopus laevis) and one toad (Amietophrynus pantherinus) of the south Western Cape Province of South Africa. Initially, different extraction techniques for the collection of skin secretions ...

  13. In vitro investigation on antifungal activity of some plant extracts ...

    African Journals Online (AJOL)

    Prof. Ogunji

    In vitro investigation on antifungal activity of some plant extracts against Pyricularia oryzae. Olufolaji, D. B.1, Adeosun, B.O.1 and Onasanya, R. O.2. 1. Department of Crop, Soil and Pest Management, The Federal University of Technology, PMB 704. Akure, Ondo state, Nigeria. 2. Department of Agriculture, Federal College ...

  14. Antifungal and anti-inflammatory effects of Coptidis rhizome extract ...

    African Journals Online (AJOL)

    Background: Coptidis rhizoma has been used as antibiotics in traditional Chinese medicine practice for many years. Here, we examined the effect of rhizoma Coptidis extract on the growth of C. albicans. Materials and Methods: The antifungal effects of Coptidis rhizoma extract was examined by time-kill assay, transmission ...

  15. in-vitro antifungal effect of garcinia kola and garlic

    African Journals Online (AJOL)

    boaz

    IN-VITRO ANTIFUNGAL EFFECT OF GARCINIA KOLA AND GARLIC (ALLIUMS. SATIVUM) ON VAGINAL ISOLATES OF CANDIDA. Adejare O. Y.1, Oduyebo O. O.2, Oladele R. O.2 , Nwaokorie F. O.3, Ogunsola F. T.2. 1Department of Medical Microbiology & Parasitology, Lagos State University Teaching Hospital. Lagos ...

  16. Antifungal activity of Parmotrema tinctorum (Delise ex Nyl.) hale and ...

    African Journals Online (AJOL)

    Lichens are composite organisms comprising of a photobiont and a mycobiont. Studies have shown that extracts and secondary metabolites from lichens exhibit various bioactivities. The present study evaluates antifungal potential of crude methanolic extract of two corticolous Parmotrema species viz. Parmotrema tinctorum ...

  17. Composition and antioxidant and antifungal activities of the ...

    African Journals Online (AJOL)

    In this study, the oil constituents of Lippia gracilis were identified by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The antioxidant and antifungal activities were also evaluated. The leaf oil showed a yield of 3.7% and its main constituents were thymol (70.3%), p-cymene (9.2%), thymol ...

  18. Antifungal metabolites from fungal endophytes of Pinus strobus

    DEFF Research Database (Denmark)

    Sumarah, Mark W; Kesting, Julie R; Sørensen, Dan

    2011-01-01

    The extracts of five foliar fungal endophytes isolated from Pinus strobus (eastern white pine) that showed antifungal activity in disc diffusion assays were selected for further study. From these strains, the aliphatic polyketide compound 1 and three related sesquiterpenes 2-4 were isolated and c...

  19. prevalence and antifungal susceptibility of candida species isolated ...

    African Journals Online (AJOL)

    User

    Nucleo, E., Zara, F. and Pagani, L. (2009). "Trends in frequency and in vitro antifungal susceptibility patterns of Candida isolates from women attending the STD outpatients clinic of a tertiary care hospital in Northern. Italy during the years 2002-2007." New. Mi- crobiol., 32(2): 199-204. Araj, G. F., Daher, N. K. and Tabborah, ...

  20. The antifungal activity and cytotoxicity of silver containing denture ...

    African Journals Online (AJOL)

    The antifungal activity and cytotoxicity of silver containing denture base material. A Kurt, G Erkose-Genc, M Uzun, Z Emrence, D Ustek, G Isik-Ozkol. Abstract. Objective: Denture base materials are susceptible to fungal adhesion, which is an important etiological issue in the pathogenesis of denture stomatitis. The purpose of ...

  1. Antifungal activity of rice straw extract on some phytopathogenic fungi

    African Journals Online (AJOL)

    The antifungal activity of allelochemicals extracted from rice straw on the radial growth rate and the activity of some hydrolyzing enzymes of Aspergillus flavus, Alternaria alternata and Botrytis cinerea were studied in vitro. Five different concentrations (2, 4, 6, 8 and 10%, w/v) of water, methanol and acetone extracts of rice ...

  2. Antifungal evaluation of shell pyrolysates of oil palm ( Elaeis ...

    African Journals Online (AJOL)

    The medicinal values of oil palm and coconut shells are not much known in herbal medicine and the two mostly constitute waste products. The antifungal effects of steam-distilled pyrolysates obtained from the two shells and the respective organic solvent fractions were evaluated against human pathogenic fungi ...

  3. Antifungal activity of methanolic root extract of Withania somnifera

    African Journals Online (AJOL)

    Proff.Adewunmi

    Background: Basal rot of onion (Allium cepa L.) caused by Fusarium oxysporum f. sp. cepae is a common soil-borne disease that causes significant yield losses. Generally, synthetic fungicides are used to combat the menace which causes environmental pollution. The present study was carried out to assess the antifungal ...

  4. Anti-fungal properties of chitinolytic dune soil bacteria

    NARCIS (Netherlands)

    De Boer, W.; Klein Gunnewiek, P.J.A.; Lafeber, P.; Janse, J.H.; Spit, B.E.; Woldendorp, J.W.

    1998-01-01

    Anti-fungal properties of chitinolytic soil bacteria may enable them to compete successfully for chitin with fungi. Additionally, the production of chitinase may be part of a lytic system that enables the bacteria to use living hyphae rather than chitin as the actual growth substrate, since chitin

  5. Antifungal activity of bacterial strains from the rhizosphere of ...

    African Journals Online (AJOL)

    user

    2011-06-08

    Jun 8, 2011 ... This study evaluated the antifungal action of biomolecules produced from the secondary metabolism of bacterial strains found in the rhizosphere of semi arid plants against human pathogenic Candida albicans. Crude extracts were obtained using ethyl acetate as an organic solvent and the bioactivity was.

  6. New small-size peptides possessing antifungal activity

    NARCIS (Netherlands)

    Garibotto, Francisco M.; Garro, Adriana D.; Masman, Marcelo F.; Rodriguez, Ana M.; Luiten, Paul G. M.; Raimondi, Marcela; Zacchino, Susana A.; Somlai, Csaba; Penke, Botond; Enriz, Ricardo D.

    2010-01-01

    The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using

  7. Evaluation of the antifungal activity of the Iranian thyme essential ...

    African Journals Online (AJOL)

    Postharvest diseases cause considerable losses to harvested fruits and vegetables during transportation and storage. The aim of this study was to evaluate the antifungal potential of Thymus danensis and Thymus carmanicus against four postharvest pathogenic fungi (Rhizopus stolonifer, Penicillium digitatum, Aspergillus ...

  8. Cinnamic acid analogs as intervention catalysts for overcoming antifungal tolerance

    Science.gov (United States)

    Antifungal potency of thirty-three cinnamic acid derivatives was investigated. The efficacy of caspofungin (CAS) or octyl gallate (OG), the cell wall disrupting agents, was augmented by 4-chloro-a-methyl- or 4-methylcinnamic acid screened. Synergistic chemosensitization by 4-chloro-a-methyl- or 4-me...

  9. Chemical Composition and Antifungal Properties of Essential Oil of ...

    African Journals Online (AJOL)

    Celular e Proteômica do Instituto de Biologia. Roberto Alcântara Gomes da Universidade. Estadual do Rio de Janeiro (UERJ), Brazil. Microbiological screening. Preliminary antifungal assays were performed. For this, fungal fragment (2 mm) was inoculated on potato dextrose agar previously incorporated with essential oil ...

  10. Antifungal and antibacterial activities of an alcoholic extract of ...

    African Journals Online (AJOL)

    Methanolic, ethanolic and petroleum ether extracts of Senna alata leaves were screened for phytochemicals, antibacterial and antifungal activities. Out of the three crude extracts, the methanolic extract showed the highest activity than the ethanolic and petroleum ether extracts. The unidentified active components purified ...

  11. Antifungal potential of leaf extracts of leguminous trees against ...

    African Journals Online (AJOL)

    In order to search environmental friendly alternatives from natural resources, methanolic extracts of three leguminous tree species namely Acacia nilotica (L.) Willd. ex Delile subsp. indica (Benth.) Brenan, Prosopis juliflora (Sw.) DC. and Albizia lebbeck (L.) Benth. were evaluated for their antifungal activity against S. rolfsii ...

  12. Antifungal activity of bacterial strains from the rhizosphere of ...

    African Journals Online (AJOL)

    This study evaluated the antifungal action of biomolecules produced from the secondary metabolism of bacterial strains found in the rhizosphere of semi arid plants against human pathogenic Candida albicans. Crude extracts were obtained using ethyl acetate as an organic solvent and the bioactivity was assessed with a ...

  13. Therapeutic potential of antifungal plant and insect defensins

    NARCIS (Netherlands)

    Thevissen, K.; Kristensen, H.H.; Thomma, B.P.H.J.; Cammue, B.P.A.; François, I.E.J.A.

    2007-01-01

    To defend themselves against invading fungal pathogens, plants and insects largely depend on the production of a wide array of antifungal molecules, including antimicrobial peptides such as defensins. Interestingly, plant and insect defensins display antimicrobial activity not only against plant and

  14. A non-polyene antifungal antibiotic from Streptomyces albidoflavus ...

    Indian Academy of Sciences (India)

    Out of these, 22% of the isolates exhibited activity against fungi. One promising strain, Streptomyces albidoflavus PU 23 with strong antifungal activity against pathogenic fungi was selected for further studies. Antibiotic was extracted and purified from the isolate. Aspergillus spp. was most sensitive to the antibiotic followed by ...

  15. Evaluation of Antioxidant and Antifungal Activities of Polyphenol-rich ...

    African Journals Online (AJOL)

    by 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) free radical scavenging activity, reducing power and in vitro lipid peroxidation (LPO). Antifungal activity was evaluated by agar-well diffusion method while mineral content was evaluated by atomic absorption spectrophotometry (AAS). Results: Significant ...

  16. Antifungal Activities of a Pasture Honey and Ginger ( Ziginber ...

    African Journals Online (AJOL)

    ... saponin and cardiac glycoside, while in the ginger sample, saponin, phlobatannin, alkaloids, flavonoids and cardiac glycoside were present. Summarily, honey and ginger extracts displayed the highest inhibitory activity on all the tested fungal isolates compared to the employed positive control antifungal (Griseofulvin and ...

  17. Antifungal activity of leaf extract of Crassocephalum repidiodes on ...

    African Journals Online (AJOL)

    The susceptibility profile of the dermatophytes tested was T. mentagrophytes. > T. rubrum > M. audouinii. The phytochemical studies of the extracts revealed that the aqueous extract lacked terpenes and anthraquinone while terpenes were absent in ethanolic extract. KEY WORDS: Antifungal, Dermatophytes, Extract, ...

  18. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    Science.gov (United States)

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Antifungal and Antihepatotoxic Effects of Sepia Ink Extract against ...

    African Journals Online (AJOL)

    Background: There is a great need for novel strategies to overcome the high mortality associated with invasive pulmonary aspergillosis (IPA) in immunocompromised patients. To evaluate the antifungal and antihepatotoxic potentials of Sepia ink extract, its effect on liver oxidative stress levels was analyzed against IPA in ...

  20. In vitro antifungal activity of Argemone ochroleuca Sweet latex ...

    African Journals Online (AJOL)

    The in vitro antifungal activities of crude latex of Argemone ochroleuca Sweet against four clinical isolates of Candida (Candida albicans, Candida glabrata, Candida krusei and Candida tropicalis) and six isolates of plant pathogenic fungi (Alternaria alternate, Drechslera halodes, Fusarium oxysporum, Macrophomina ...

  1. Antifungal Capacity of Lactic Acid Bacteria Isolated From Salad ...

    African Journals Online (AJOL)

    This study explores the use of lactic acid bacteria from fresh salad vegetables to inhibit fungal growth. The antifungal assay was done using the agar well diffusion method as reported by Schillinger and Lucke (1989). The largest zone of inhibition (25mm) was recorded by the antagonistic activity of the isolate identified to ...

  2. In vitro antifungal activity of methanol extracts of some Indian ...

    African Journals Online (AJOL)

    The methanol extract of 9 Indian medicinal plants belonging to 9 different families were evaluated for in vitro antifungal activity against some yeasts including Candida albicans (1) ATCC2091, C. albicans (2) ATCC18804, Candida glabrata NCIM3448, Candida tropicalis ATCC4563, Cryptococcus luteolus ATCC32044, ...

  3. Comparative study of the antifungal activity of some essential oils ...

    African Journals Online (AJOL)

    This study aimed to evaluate the antimould activity of oregano, thyme, rosemary and clove essential oils and some of their main constituents: eugenol, carvacrol and thymol against Aspergillus niger. This antifungal activity was assessed using broth dilution, disc diffusion and micro atmosphere methods. In both agar diffusion ...

  4. Antifungal and antibacterial activities of the ethanolic and aqueous ...

    African Journals Online (AJOL)

    SERVER

    2007-07-18

    Jul 18, 2007 ... psoriasis and eczema, through to the more serious disease like leprosy, syphilis and skin cancer (Burkill,. 1985). Previous studies of the fruits of K. africana showed some antibacterial activity (Grace et al., 2002). However there is no report on the antibacterial and antifungal properties of the stem bark of this ...

  5. Evaluation of Antioxidant and Antifungal Activities of Polyphenol-rich ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antioxidant and antifungal activities of polyphenol-rich extracts of the dried fruit pulp of Garcinia pedunculata (GP) and Garcinia morella (GM) to determine their traditional claims of therapeutic activity against certain diseases. Methods: Analysis of total phenolic (TP) and flavonoid (TF) contents of the ...

  6. Synthesis and Antifungal Activities of Some Novel Pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Dequn Sun

    2011-06-01

    Full Text Available Three series of new pyrimidine derivatives were synthesized and their antifungal activities were evaluated in vitro against fourteen phytopathogenic fungi. The results indicated that most of the synthesized compounds possessed fungicidal activities and some of them are more potent than the control fungicides. Preliminary SAR was also discussed.

  7. Antifungal activity of methanolic extracts of four Algerian marine ...

    African Journals Online (AJOL)

    cmi

    2012-05-15

    May 15, 2012 ... and antifungal activities of the extracts of marine algae from southern coast of India. Botanica marina. 40: 507-515. Patra JK, Patra AP, Mahapatra NK, Thatoi HN, Das S, Sahu, RK, Swain. GC (2009). Antimicrobial activity of organic solvent extracts of three marine macroalgae from Chilika Lake, Orissa, India.

  8. The Antifungal Activity and Cytotoxicity of Silver Containing Denture ...

    African Journals Online (AJOL)

    2015-10-30

    Oct 30, 2015 ... cytotoxicity of denture base material containing silver microparticles. Materials and Methods: The polymethyl methacrylate (PMMA) denture base material was used, and silver microparticles were added to the polymer ... The antifungal properties of these. A Kurt, G Erkose-Genc1, M Uzun1, Z Emrence2, ...

  9. Antifungal activity of methanolic root extract of Withania sommnifera ...

    African Journals Online (AJOL)

    The present study was carried out to assess the antifungal activity of Withania somnifera (L.), Dunal, a Solanaceous medicinal plant, against the pathogen of this disease. Materials and Methods: Different concentrations (from 0.5 to 4%) of methanolic extract of root stem and fruit of the test plant species were prepared and ...

  10. Evaluation of antifungal activity from Bacillus strains against ...

    African Journals Online (AJOL)

    In this study, 30 bacterial strains isolated from marine biofilms were screened for their antifungal activity against Rhizoctonia solani by dual culture assay. Two bacterial strains, Bacillus subtilis and Bacillus cereus, showed a clear antagonism against R. solani on potato dextrose agar (PDA) medium. The antagonistic activity ...

  11. Investigation on the antifungal properties of freshly pressed garlic ...

    African Journals Online (AJOL)

    Background : Modern science is tending to confirm many of the beliefs of ancient cultures regarding efficacy of garlic. In this paper we report the antifungal effects of freshly pressed juice of garlic on the major pathogenic fungi. Methods: Freshly pressed juice of varying concentrations of garlic were assessed for their ...

  12. Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles.

    Science.gov (United States)

    Hu, Chengcheng; Zhou, Mi; Wang, Wenzhao; Sun, Xianyun; Yarden, Oded; Li, Shaojie

    2018-01-01

    Fungi transcriptionally upregulate expression of azole efflux pumps and ergosterol biosynthesis pathway genes when exposed to antifungal agents that target ergosterol biosynthesis. To date, these transcriptional responses have been shown to be dependent on the presence of the azoles and/or depletion of ergosterol. Using an inducible promoter to regulate Neurospora crassa erg11 , which encodes the major azole target, sterol 14α-demethylase, we were able to demonstrate that the CDR4 azole efflux pump can be transcriptionally activated by ergosterol biosynthesis inhibition even in the absence of azoles. By analyzing ergosterol deficient mutants, we demonstrate that the transcriptional responses by cdr4 and, unexpectedly, genes encoding ergosterol biosynthesis enzymes ( erg genes) that are responsive to azoles, are not dependent on ergosterol depletion. Nonetheless, deletion of erg2 , which encodes C-8 sterol isomerase, also induced expression of cdr4 . Deletion of erg2 also induced the expression of erg24 , the gene encoding C-14 sterol reductase, but not other tested erg genes which were responsive to erg11 inactivation. This indicates that inhibition of specific steps of ergosterol biosynthesis can result in different transcriptional responses, which is further supported by our results obtained using different ergosterol biosynthesis inhibitors. Together with the sterol profiles, these results suggest that the transcriptional responses by cdr4 and erg genes are associated with accumulation of specific sterol intermediate(s). This was further supported by the fact that when the erg2 mutant was treated with ketoconazole, upstream inhibition overrode the effects by downstream inhibition on ergosterol biosynthesis pathway. Even though cdr4 expression is associated with the accumulation of sterol intermediates, intra- and extracellular sterol analysis by HPLC-MS indicated that the transcriptional induction of cdr4 did not result in efflux of the accumulated intermediate

  13. Discovery of an Octahedral Silicon Complex as a Potent Antifungal Agent.

    Science.gov (United States)

    Fu, Chen; Fu, Bin; Peng, Xixi; Liao, Guojian

    2017-04-15

    Octahedral transition metal complexes have been shown to have tremendous applications in chemical biology and medicinal chemistry. Meanwhile, structural transition metals can be replaced by inert octahedral silicon in a proof-of-principle study. We here introduce the first example of octahedral silicon complexes, which can very well serve as an efficient antimicrobial agent. The typical silicon arenediolate complex 1 {[(phen)₂Si(OO)](PF₆)₂, with phen = 1,10-phenanthroline, OO = 9,10-phenanthrenediolate} exhibited significant inhibition towards the growth of Cryptococcus neoformans with MIC and MFC values of 4.5 and 11.3 μM, respectively. Moreover, it was fungicidal against both proliferative and quiescent Cryptococcus cells. This work may set the stage for the development of novel antifungal drugs based upon hexacoodinate silicon scaffolds.

  14. Chemical composition, cytotoxicity, antimicrobial and antifungal activity of several essential oils.

    Science.gov (United States)

    Cannas, Sara; Usai, Donatella; Tardugno, Roberta; Benvenuti, Stefania; Pellati, Federica; Zanetti, Stefania; Molicotti, Paola

    2016-01-01

    Essential oils (EOs) are known and used for their biological, antibacterial, antifungal and antioxidant properties. Numerous studies have shown that EOs exhibit a large spectrum of biological activities in vitro. The incidence of drug-resistant pathogens and the toxicity of antibiotics have drawn attention to the antimicrobial activity of natural products, encouraging the development of alternative treatments. The aim of this study was to analyse the phytochemical and the cytotoxic characteristic of 36 EOs; we then evaluated the antimicrobial activity of the less-toxic EOs on Gram-positive, Gram-negative and fungi strains. The results showed low cytotoxicity in seven EOs and good activity against Gram-negative and Candida spp. strains. Based on our results, EOs could be proposed as a novel group of therapeutic agents. Further experiments are necessary to confirm their pharmacological effectiveness, and to determine potential toxic effects and the mechanism of their activity in in vivo models.

  15. Routine versus selective antifungal administration for control of fungal infections in patients with cancer

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2014-01-01

    commonly used antifungal drugs decrease mortality in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole....... Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found.......73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial...

  16. Antibacterial and antifungal screening of the root extracts of nardostachys jatamansi

    International Nuclear Information System (INIS)

    Sohail, T.; Yaqeen, Z.; Imran, H.; Shaukat, S.

    2007-01-01

    Antimicrobial activity of ethanol, ethyl acetate and hexane extracts of Nardostachys roots were studied in vitro against six pathogenic gram positive bacteria (Stayphylococcus aureus, streptococcus intermedius, S. faecalis, Bacillus Pumilus, B. cereus B. subtilus), six gram negative bacteria (Escherichia coli, Salmonella typhi, S. Paratyphi B, Klebsiella Pneumoniae, Proteus mirabilus, Shigella flexneri) and five fungi (Trichophyton rubrum, T. schoenleinii, Aspergillus niger, Candida albicans, C. glabrata). Ethanolic root extract exhibited maximum antimicrobial activity against all the tested bacteria and gungi, at concentration of 5, 10 and 20 mg/ml as compared to ethyl acetate and hexane extract, which did not show marked activity. Antimicrobial activity was compared with the activities of standard antibacterial and antifungal drugs, namely Ampicillin and Nystatin, respectively. The minimum inhibitory concentration (MIC) were between 0.5-1 mg/ml against all the studied microorganisms. (author)

  17. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

    Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

  18. Antifungal proteins and peptides of leguminous and non-leguminous origins.

    Science.gov (United States)

    Ng, T B

    2004-07-01

    Antifungal proteins and peptides, as their names imply, serve a protective function against fungal invasion. They are produced by a multitude of organisms including leguminous flowering plants, non-leguminous flowering plants, gymnosperms, fungi, bacteria, insects and mammals. The intent of the present review is to focus on the structural and functional characteristics of leguminous, as well as non-leguminous, antifungal proteins and peptides. A spectacular diversity of amino acid sequences has been reported. Some of the antifungal proteins and peptides are classified, based on their structures and/or functions, into groups including chitinases, glucanases, thaumatin-like proteins, thionins, and cyclophilin-like proteins. Some of the well-known proteins such as lectins, ribosome inactivating proteins, ribonucleases, deoxyribonucleases, peroxidases, and protease inhibitors exhibit antifungal activity. Different antifungal proteins may demonstrate different fungal specificities. The mechanisms of antifungal action of only some antifungal proteins including thaumatin-like proteins and chitinases have been elucidated.

  19. Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

    Science.gov (United States)

    Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  20. Antifungal and immunomodulatory activity of a novel cochleate for amphotericin B delivery against Sporothrix schenckii.

    Science.gov (United States)

    Batista-Duharte, A; Lastre, M; Romeu, B; Portuondo, D L; Téllez-Martínez, D; Manente, F A; Pérez, O; Carlos, I Z

    2016-11-01

    Sporotrichosis is an emergent subcutaneous mycoses caused by species of the Sporothrix schenckii complex. Amphotericin B (AmB) remains the main antifungal drug for the treatment of systemic infections, but its use is limited by toxicity reasons. AFCo3 is a novel cochleate containing detoxified LPS, which exhibits drug delivery and immunomodulating properties. Here, AFCo3 was used as the vehicle for AmB to evaluate the immunomodulatory and antifungal efficacy against S. schenckii in vitro and in vivo. The minimum inhibitory concentrations of AFCo3-AmB and AmB were 0.25 and 1μg/mL respectively. The minimum fungicidal concentration was 0.5μg/mL for AFCo3-AmB and 2μg/mL for AmB. AFCo3-AmB was less cytotoxic than AmB for peritoneal macrophages, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and reduced the AmB-induced hemolysis in murine erythrocytes. AFCo3-AmB improved the intracellular killing of phagocytized yeast and it enhanced the in vitro production of IL-1β, TNF-α and NO in peritoneal macrophages. Moreover, AFCo3-AmB was more effective than AmB in reducing spleen and liver fungal burden after repeated (five days) intraperitoneal administration of 5mg/kg of AmB, in a Balb/c model of systemic infection, associated to a significant induction of Th1/Th17 response. Finally, blood chemistry revealed that AFCo3-AmB did not cause changes suggestive of nephrotoxicity, such as increases in total proteins, albumin, creatinine and blood urea nitrogen that were caused by free AmB. AFCo3-AmB exhibited a significant immunomodulator action, reduced toxicity and improved antifungal action against S. schenckii, suggesting a potential use as AmB delivery for systemic sporotrichosis treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Antifungal activity of essential oils against selected terverticillate penicillia

    Directory of Open Access Journals (Sweden)

    Soňa Felšöciová

    2015-02-01

    Full Text Available The aim of this study was to screen 15 essential oils of selected plant species, viz. [i]Lavandula angustifolia[/i], [i]Carum carvi[/i], [i]Pinus mungo var. pulmilio[/i], [i]Mentha piperita[/i], [i]Chamomilla recutita[/i] L.,[i] Pinus sylvestris[/i], [i]Satureia hortensis[/i] L., [i]Origanum vulgare[/i] L., [i]Pimpinella anisum[/i], [i]Rosmarinus officinali[/i]s L., [i]Salvia officinalis[/i] L., [i]Abietis albia etheroleum[/i], [i]Chamomilla recutita[/i] L. [i]Rausch[/i], [i]Thymus vulgaris[/i] L., [i]Origanum vulgare[/i] L. for antifungal activity against five [i]Penicillium[/i] species: [i]Penicillium brevicompactum[/i], [i]Penicillium citrinum[/i], [i]Penicillium crustosum[/i], [i]Penicillium expansum[/i] and [i]Penicillium griseofulvum[/i]. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against [i]Penicillium[/i] fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: [i]Pimpinella anisum[/i], [i]Chamomilla recutita[/i] L., [i]Thymus vulgaris[/i], [i]Origanum vulgare[/i] L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be [i]Origanum vulgare[/i] L. and [i]Pimpinella anisum[/i]. The lowest level of antifungal activity was demonstrated by the oils [i]Pinus mungo var. pulmilio[/i], [i]Salvia officinalis[/i] L., [i]Abietis albia etheroleum[/i], [i]Chamomilla recutita[/i] L.[i] Rausch[/i], [i]Rosmarinus officinalis[/i].

  2. Sporothrix schenckii complex in Iran: Molecular identification and antifungal susceptibility.

    Science.gov (United States)

    Mahmoudi, Shahram; Zaini, Farideh; Kordbacheh, Parivash; Safara, Mahin; Heidari, Mansour

    2016-08-01

    Sporotrichosis is a global subcutaneous fungal infection caused by the Sporothrix schenckii complex. Sporotrichosis is an uncommon infection in Iran, and there have been no phenotypic, molecular typing or antifungal susceptibility studies of Sporothrix species. This study aimed to identify nine Iranian isolates of the S. schenckii complex to the species level using colony morphology, carbohydrate assimilation tests, and PCR-sequencing of the calmodulin gene. The antifungal susceptibilities of these Sporothrix isolates to five antifungal agents (amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and terbinafine (TRB)) were also evaluated according to the M27-A3 and M38-A2 protocols of the Clinical and Laboratory Standards Institute for yeast and mycelial phases, respectively. Five of seven clinical isolates were identified as S. schenckii, and two clinical and two environmental isolates were identified as S. globosa. This is the first report of S. globosa in Iran. There was significant agreement (73%) between the results of the phenotypic and genotypic identification methods. TRB and ITC were the most effective antifungals against the Sporothrix isolates. The minimum inhibitory concentration (MIC) values of TRB for the yeast and mycelial phases of S. schenckii differed significantly. There was also a significant difference in the minimum fungicidal concentration (MFC) values of AMB and TRB for the two phases. Considering the low efficacy of VRC and FLC and the wide MIC ranges of AMB (1-16 μg/ml and 1-8 μg/ml for yeast and mycelial forms, respectively) observed in the present study, in vitro antifungal susceptibility testing should be performed to determine appropriate therapeutic regimens. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Investigation of the antifungal potential of linalool against clinical isolates of fluconazole resistant Trichophyton rubrum.

    Science.gov (United States)

    de Oliveira Lima, M I; Araújo de Medeiros, A C; Souza Silva, K V; Cardoso, G N; de Oliveira Lima, E; de Oliveira Pereira, F

    2017-06-01

    The aim of this study was to investigate the activity of the monoterpene linalool against clinical isolates of Trichophyton rubrum. Initially, a sensitivity assay for commercial antifungals with solid disks in diffusion medium was performed. Minimum inhibitory concentration (MIC) of linalool and ketoconazole (positive control) were determined by microdilution in RPMI 1640 medium (CLSI M38-A2). We then evaluated the action of linalool and ketoconazole at different concentrations (1/2MIC, MIC and 2×MIC) on mycelial growth (radial mycelial growth), conidia production and conidia germination using a hemacytometer. The effects on cell membrane (release of intracellular material) were also investigated. Finally, changes in fungal morphology as induced by the test drugs were analyzed. Based on the sensitivity tests, the fungal strains showed resistance to 5-fluorocytosine and fluconazole. The linalool MIC values ranged from 256μg/mL to 512μg/mL, whereas ketoconazole showed values of 4μg/mL to 8μg/mL. For the LM 305 strain, the test drugs showed the following MIC values: linalool 256μg/mL and ketoconazole 8μg/mL. The mycelial growth of T. rubrum LM 305 was inhibited by linalool (2×MIC) and ketoconazole (1/2MIC, MIC, 2×MIC), in 7 days of treatment (PLinalool also caused leakage of intracellular material (Plinalool and ketoconazole to induce micro-morphological changes, forming abnormal, wide, short and crooked hyphae. Based on these results, we conclude that linalool presents as an antifungal agent with anti-Trichophyton rubrum potential, an important dermatophytosis agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. The Antifungal Inhibitory Concentration Effectiveness Test From Ethanol Seed Arabica Coffee (Coffea arabica) Extract Against The Growth Of Candida albicans Patient Isolate With In Vitro Method

    Science.gov (United States)

    Satria Rakatama, Adam; Pramono, Andri; Yulianti, Retno

    2018-03-01

    Candida albicans are the most frequent cause of Vulvovaginalis Candidiasis infection. Its treatment using antifungal drugs, are oftenly caused side effects. The reduction of C.albicans growth and the reduction of antifungal drugs side effect, were our main purposed. Our study objective is determine the effectiveness of inhibitory power of arabica coffee seed ethanol extract on the growth of C.albicans patient isolates. The type of this research is experimental research. Kirby-bauer method with the Saboraud Dextrose Agar (SDA) media was used in this experiment. Inhibitory zone was observed around the disc, to determine the inhibitory power. The results showed that the inhibitory zone was formed on arabica coffee seed ethanol extract on 10%, 20%, 40%, and 80% concentration. Kruskal-Wallis test results (palbicans patient isolates were smaller compared with C.albicans ATCC 90028 as gold standard. This showed that the virulence of C.albicans from patients isolates were higher. We concluded that arabica coffee seed ethanol extract could inhibiting the growth of C.albicans patient isolates. Optimization of coffee seed ethanol extract to obtain maximum active ingredients still needs to be done. This knowledge is expected to be used for the beginning manufacturer antifungal drug from natural product.

  5. Changes in germ tube formation and cell-surface hydrophobicity of oral Candida dubliniensis isolates following brief exposure to sub-cidal concentrations of polyene and azole antifungal agents.

    Science.gov (United States)

    Ellepola, Arjuna N B; Joseph, Bobby K; Khan, Z U

    2013-07-01

    Adherence of Candida has been implicated as the initial process in the pathogenesis of oral candidosis. Candidal germ tubes and its relative cell-surface hydrophobicity (CSH) are contributory attributes. Candida dubliniensis is currently documented as an opportunistic pathogen allied with recurrent oral candidosis. Oral candidosis can be treated with polyene and azole antifungals such as amphotericin B, ketoconazole and fluconazole. However, the intraoral concentration of these drugs fluctuates and becomes sub-therapeutic because of the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intraorally, the pathogenic yeast may undergo a brief exposure to antifungal drugs. The objective of this study was to investigate the effect of brief exposure to sub-lethal concentrations of these antifungals on the germ tube formation and CSH of C. dubliniensis. After determining the minimum inhibitory concentration of the drugs, 20 oral isolates of C. dubliniensis were exposed to sub-lethal concentrations of these antifungals for 1 h. Following this brief exposure, the drugs were removed, and following subsequent incubation in a germ tube inducing medium and exposure to bi-phasic hydrocarbon assay, the germ tube formation and CSH of these isolates was quantified respectively. Compared with controls, exposure to amphotericin B almost completely suppressed the ability to form germ tubes with a mean percentage reduction of 95.91% (P formation but to a lesser degree with a mean percentage reduction of 18.73% and 12.01% respectively (P  0.05). In clinical terms it appears that, even a short exposure to sub-lethal concentrations of these drugs, a situation all too familiar in the oral environment, would continue to exert an antifungal effect by suppressing the pathogenic potency of C. dubliniensis. © 2013 Blackwell Verlag GmbH.

  6. D19S Mutation of the Cationic, Cysteine-Rich Protein PAF: Novel Insights into Its Structural Dynamics, Thermal Unfolding and Antifungal Function.

    Science.gov (United States)

    Sonderegger, Christoph; Fizil, Ádám; Burtscher, Laura; Hajdu, Dorottya; Muñoz, Alberto; Gáspári, Zoltán; Read, Nick D; Batta, Gyula; Marx, Florentine

    2017-01-01

    The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research. To understand its mode of action, we started to investigate the surface-exposed loops of PAF and replaced one aspartic acid at position 19 in loop 2 that is potentially involved in PAF active or binding site, with a serine (Asp19 to Ser19). We analysed the overall effects, such as unfolding, electrostatic changes, sporadic conformers and antifungal activity when substituting this specific amino acid to the fairly indifferent amino acid serine. Structural analyses revealed that the overall 3D solution structure is virtually identical with that of PAF. However, PAFD19S showed slightly increased dynamics and significant differences in the surface charge distribution. Thermal unfolding identified PAFD19S to be rather a two-state folder in contrast to the three-state folder PAF. Functional comparison of PAFD19S and PAF revealed that the exchange at residue 19 caused a dramatic loss of antifungal activity: the binding and internalization of PAFD19S by target cells was reduced and the protein failed to trigger an intracellular Ca2+ response, all of which are closely linked to the antifungal toxicity of PAF. We conclude that the negatively charged residue Asp19 in loop 2 is essential for full function of the cationic protein PAF.

  7. Clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in HIV patients: a single Mexican center experience.

    Science.gov (United States)

    Villanueva-Lozano, Hiram; Treviño-Rangel, Rogelio de J; González, Gloria M; Hernández-Rodríguez, Pedro A; Camacho-Ortiz, Adrián; Castillo-Reyna, Luis; Galindo-Alvarado, Sandra G; Martínez-Reséndez, Michel F

    2018-02-01

    Cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among HIV/AIDS patients. The first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin B plus flucytosine. However, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. This is a prospective, double-blinded, and randomized study performed in a Mexican tertiary care center to evaluate the antifungal activity of sertraline in the treatment of cryptococcal meningitis in HIV patients. During June 2015-December 2016, patients were recruited and included in one of two study groups: group A was given standard antifungal treatment plus sertraline 200 mg/day, while group B was given standard antifungal plus placebo. Lumbar punctures were performed on days 0, 7, and 14 of the study, and cryptococcal antigenemia and quantitative fungal culture in cerebrospinal fluid at each time point were evaluated to measure the rate of fungal clearance. The fungal loads and cryptococcal antigenemia titers showed a marked tendency to decrease by day 14 in both groups. Otherwise, group B exhibited a slightly higher nonstatistical rate of fungal clearance (-0.2868 ± 0.08275 log CFU/ml/day) than group A (-0.2496 ± 0.08340 log CFU/ml/day). A statistical difference between study groups was not found. This is the first study in Latin America that reports the experience of using sertraline as an adjuvant in the antifungal management of cryptococcal meningitis in HIV patients.

  8. New insights into the structure and mode of action of Mo-CBP3, an antifungal chitin-binding protein of Moringa oleifera seeds.

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    Adelina B Batista

    Full Text Available Mo-CBP3 is a chitin-binding protein purified from Moringa oleifera Lam. seeds that displays inhibitory activity against phytopathogenic fungi. This study investigated the structural properties and the antifungal mode of action of this protein. To this end, circular dichroism spectroscopy, antifungal assays, measurements of the production of reactive oxygen species and microscopic analyses were utilized. Mo-CBP3 is composed of 30.3% α-helices, 16.3% β-sheets, 22.3% turns and 30.4% unordered forms. The Mo-CBP3 structure is highly stable and retains its antifungal activity regardless of temperature and pH. Fusarium solani was used as a model organism for studying the mechanisms by which this protein acts as an antifungal agent. Mo-CBP3 significantly inhibited spore germination and mycelial growth at 0.05 mg.mL-1. Mo-CBP3 has both fungistatic and fungicidal effects, depending on the concentration used. Binding of Mo-CBP3 to the fungal cell surface is achieved, at least in part, via electrostatic interactions, as salt was able to reduce its inhibitory effect. Mo-CBP3 induced the production of ROS and caused disorganization of both the cytoplasm and the plasma membrane in F. solani cells. Based on its high stability and specific toxicity, with broad-spectrum efficacy against important phytopathogenic fungi at low inhibitory concentrations but not to human cells, Mo-CBP3 has great potential for the development of new antifungal drugs or transgenic crops with enhanced resistance to phytopathogens.

  9. Is antifungal resistance a cause for treatment failure in dermatophytosis: A study focused on tinea corporis and cruris from a tertiary centre?

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    Kabir Sardana

    2018-01-01

    Full Text Available Background: Dermatophytoses are one of the most common skin diseases that have been largely simple to treat. However, in recent years, these infections have become recalcitrant to treatment which can possibly be due to antifungal resistance. Aim: To analyze the resistance pattern of patients with recalcitrant dermatophytoses. Materials and Methods: A cross-sectional evaluation was undertaken of 40 consecutive patients with recalcitrant tinea corporis/cruris/both who had taken systemic antifungal treatment and did not respond completely to therapy or had recurrent lesion within 1 month of stopping the therapy. Terbinafine, fluconazole, itraconazole, ketoconazole, amphotericin B, and voriconazole were the antifungals tested using broth microdilution assay for antifungal susceptibility testing of dermatophytes, and MIC50, 90 values were recorded. Results: KOH mount was positive in 18 (45% patients, culture was positive in 28 (70% patients. Trichophyton mentagrophytes (35% and T. rubrum (27.5% were the predominant isolates. Overall, activity of terbinafine and itraconazole were significantly higher than the other drugs tested. For terbinafine, both T. mentagrophytes and T. rubrum were inhibited at MIC90of 0.125 μg/ml. Itraconazole-inhibited T. mentagrophytes and T. rubrum at MIC90of 0.0625 and 0.25 μg/ml, respectively. All isolates had reduced susceptibility to fluconazole. Conclusion: While MIC seen were higher than western data, in-vitro resistance (>1 μg/ml to antifungals was not seen and probably may not be a cause of treatment failure. Possibly, treatment failure lies in the intricate host fungal interaction and virulence of species which help it to evade host immune response.

  10. Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans.

    Science.gov (United States)

    Shi, Dongmei; Zhao, Yaxin; Yan, Hongxia; Fu, Hongjun; Shen, Yongnian; Lu, Guixia; Mei, Huan; Qiu, Ying; Li, Dongmei; Liu, Weida

    2016-05-01

    Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.

  11. Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy-substituted phenyl-3-((phenylaminomethyl-1,3,4-oxadiazole-2(3H-thiones

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    Urja D. Nimbalkar

    2016-05-01

    Full Text Available A novel series of 5-(4-(benzyloxysubstituted phenyl-3-((phenyl aminomethyl-1,3,4-oxadiazole-2(3H-thione Mannich bases 6a–o were synthesized in good yield from the key compound 5-(4-(benzyloxyphenyl-1,3,4-oxadiazole-2(3H-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.

  12. Antibacterial, antifungal, insecticidal, cytotoxicity and phytotoxicity studies on Indigofera gerardiana.

    Science.gov (United States)

    Nisar, Muhammad; Tariq, Shafiq Ahmad; Marwat, Inamullah Khan; Shah, Muhammad Raza; Khan, Ihsan Ali

    2009-02-01

    The antibacterial, antifungal, acute cytotoxicity, phytotoxicity and insecticidal profile of the crude extract and various fractions of Indigofera gerardiana have been studied. Six bacterial and fungal strains were used, of which Samonella typhi and Microsporum canis were the most susceptible strains with MICs 0.37 mg/mL and 0.09 mg/mL, respectively. The crude extract and the fractions showed low insecticidal activity against Sitophilus oryzae, Rhyzopertha dominica and Callosbruchus analis but no activity against Tribolium castaneum. The brine shrimp lethality assay showed absence of any measurable cytotoxicity of the crude extract and fractions, showing a good safety profile at a preliminary level. All the fractions except crude extract revealed profound and highly significant herbicidal activity against Lemna minor at the concentration of 1000 microg/mL. Indigofera gerardiana was shown by in-vitro assays to be a potential source for natural antifungal, antibacterial and herbicidal agents.

  13. Synthesis of heterocycle-attached methylidenebenzenesulfonohydrazones as antifungal agents.

    Science.gov (United States)

    Gao, Zhinan; Lv, Min; Li, Qin; Xu, Hui

    2015-11-15

    A series of heterocycle-attached methylidenebenzenesulfonohydrazone derivatives were synthesized and evaluated for their antifungal activities against seven phytopathogenic fungi such as Fusarium graminearum, Alternaria solani, Valsa mali, Phytophthora capsici, Fusarium solani, Botrytis cinerea, and Glomerella cingulata. Compounds 7b, 8d, 9a, 9b and 9d exhibited a good and broad-spectrum of antifungal activities against at least five phytopathogenic fungi at the concentration of 100 μg/mL. It demonstrated that addition of one double bond between the phenylsulfonylhydrazone fragment and the furan ring of 6a,b,d could afford more active compounds 9a,b,d; however, introduction of the nitro group on the phenyl ring of 6a-9a gave less potent compounds 6e-9e. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Chemical Constituents and Antifungal Activity of Ficus hirta Vahl. Fruits

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    Chunpeng Wan

    2017-09-01

    Full Text Available Phytochemical investigation of Ficus hirta Vahl. (Moraceae fruits led to isolate two carboline alkaloids (1 and 2, five sesquiterpenoids/norsesquiterpenoids (3–7, three flavonoids (8–10, and one phenylpropane-1,2-diol (11. Their structures were elucidated by the analysis of their 1D and 2D NMR, and HR-ESI-MS data. All of the isolates were isolated from this species for the first time, while compounds 2, 4–6, and 8–11 were firstly reported from the genus Ficus. Antifungal assay revealed that compound 8 (namely pinocembrin-7-O-β-d-glucoside, a major flavonoid compound present in the ethanol extract of F. hirta fruits, showed good antifungal activity against Penicillium italicum, the phytopathogen of citrus blue mold caused the majority rotten of citrus fruits.

  15. Antifungal activity of nicotine and its cadmium complex

    International Nuclear Information System (INIS)

    Zaidi, I.M.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cd(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activities against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cadmium(II) iodide was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine is quite effective against the rare pathogenic and Non pathogenic fungi but comparatively less effective against Pathogenic fungi. Nicotine was found to be completely ineffective against the selected species of Occasional pathogenic fungi. Cadmium(II) iodide effectively inhibited Pathogenic and Non pathogenic fungi whereas relatively ineffective against the Occasional pathogenic and Rare pathogenic fungi. On the other hand, Cadmium(II) nicotine complex inhibited all the selected species of fungi except Fusarium solani. (author)

  16. Synthesis and antifungal evaluation of PCA amide analogues.

    Science.gov (United States)

    Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

    2018-04-18

    To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

  17. Mosquitocidal, nematicidal, and antifungal compounds from Apium graveolens L. seeds.

    Science.gov (United States)

    Momin, R A; Nair, M G

    2001-01-01

    The methanolic extract of Apium graveolens seeds was investigated for bioactive compounds and resulted in the isolation and characterization of mosquitocidal, nematicidal, and antifungal compounds sedanolide (1), senkyunolide-N (2), and senkyunolide-J (3). Their structures were determined by 1H and 13C NMR spectral methods. Compounds 1-3 gave 100% mortality at 25, 100, and 100 microg mL(-1), respectively, on the nematode, Panagrellus redivivus. Compound 1 showed 100% mortality at 50 microg mL(-1) on nematode, Caenorhabditis elegans, and fourth-instar mosquito larvae, Aedes aegyptii. Also, it inhibited the growth of Candida albicans and Candida parapsilasis at 100 microg mL(-1). Compounds 2 and 3 were isolated for the first time from A. graveolens. This is the first report of the mosquitocidal, nematicidal, and antifungal activities of compounds 1-3.

  18. Methodological Issues in Antifungal Susceptibility Testing of Malassezia pachydermatis

    Science.gov (United States)

    Peano, Andrea; Pasquetti, Mario; Tizzani, Paolo; Chiavassa, Elisa; Guillot, Jacques; Johnson, Elizabeth

    2017-01-01

    Reference methods for antifungal susceptibility testing of yeasts have been developed by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antibiotic Susceptibility Testing (EUCAST). These methods are intended to test the main pathogenic yeasts that cause invasive infections, namely Candida spp. and Cryptococcus neoformans, while testing other yeast species introduces several additional problems in standardization not addressed by these reference procedures. As a consequence, a number of procedures have been employed in the literature to test the antifungal susceptibility of Malassezia pachydermatis. This has resulted in conflicting results. The aim of the present study is to review the procedures and the technical parameters (growth media, inoculum preparation, temperature and length of incubation, method of reading) employed for susceptibility testing of M. pachydermatis, and when possible, to propose recommendations for or against their use. Such information may be useful for the future development of a reference assay. PMID:29371554

  19. Inhibitors of amino acids biosynthesis as antifungal agents.

    Science.gov (United States)

    Jastrzębowska, Kamila; Gabriel, Iwona

    2015-02-01

    Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

  20. Antifungal Activity from Leaves of Acacia Nilotica against Pythium Aphanidermatum

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    A. J. Khan

    1996-01-01

    Full Text Available Gallic acid and methyl ester of gallic acid has been identified as antifungal compounds against the mycelial growth of Pythium aphanidermatum from acetone-water extracts of Acacia nilotica leaves. The growth of fungus was completely ceased by gallic acid and its methyl ester at 1000 ppm and 750 ppm, respectively. Antifungal properties of both compounds were found to be higher in combination than alone. The minimum inhibitory concentration for both compounds was 1000 ppm. No phytotoxic effect of the compounds was observed on watermelon seed germination. The growth of roots and shoots of watermelon seedlings was promoted by gallic acid but decreased with methyl ester of gallic acid. Nitrate reductase activity of the fungus was significantly inhibited by both compounds.