scholarly journals 2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Níura Madalena Bila ◽  
Caroline Barcelos Costa-Orlandi ◽  
Carolina Orlando Vaso ◽  
Jean Lucas Carvalho Bonatti ◽  
Letícia Ribeiro de Assis ◽  
...  
Keyword(s):  
Early Stage ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Antifungal Drugs ◽  
Drug Candidate ◽  
Planktonic Cells ◽  
Sem Images ◽  
Planktonic Form ◽  
Cytoplasmic Content ◽  
Apoptosis And Necrosis

Dermatophytes, fungi that cause dermatophytosis, can invade keratinized tissues in humans and animals. The biofilm-forming ability of these fungi was described recently, and it may be correlated with the long treatment period and common recurrences of this mycosis. In this study, we evaluated the anti-dermatophytic and anti-biofilm activity of 2-hydroxychalcone (2-chalcone) in the dark and photodynamic therapy (PDT)-mediated and to determine its mechanism of action. Trichophyton rubrum and Trichophyton mentagrophytes strains were used in the study. The antifungal susceptibility test of planktonic cells, early-stage biofilms, and mature biofilms were performed using colorimetric methods. Topographies were visualized by scanning electron microscopy (SEM). Human skin keratinocyte (HaCat) monolayers were also used in the cytotoxicity assays. The mechanisms of action of 2-chalcone in the dark and under photoexcitation were investigated using confocal microscopy and the quantification of ergosterol, reactive oxygen species (ROS), and death induction by apoptosis/necrosis. All strains, in the planktonic form, were inhibited after treatment with 2-chalcone (minimum inhibitory concentration (MIC) = 7.8-15.6 mg/L), terbinafine (TRB) (MIC = 0.008–0.03 mg/L), and fluconazole (FLZ) (1–512 mg/L). Early-stage biofilm and mature biofilms were inhibited by 2-chalcone at concentrations of 15.6 mg/L and 31.2 mg/L in all tested strains. However, mature biofilms were resistant to all the antifungal drugs tested. When planktonic cells and biofilms (early-stage and mature) were treated with 2-chalcone-mediated PDT, the inhibitory concentrations were reduced by four times (2–7.8 mg/L). SEM images of biofilms treated with 2-chalcone showed cell wall collapse, resulting from a probable extravasation of cytoplasmic content. The toxicity of 2-chalcone in HaCat cells showed higher IC50 values in the dark than under photoexcitation. Further, 2-chalcone targets ergosterol in the cell and promotes the generation of ROS, resulting in cell death by apoptosis and necrosis. Overall, 2-chalcone-mediated PDT is a promising and safe drug candidate against dermatophytes, particularly in anti-biofilm treatment.

scholarly journals Identification of Promising Antifungal Drugs against Scedosporium and Lomentospora Species after Screening of Pathogen Box Library

2021 ◽  
Vol 7 (10) ◽  
pp. 803
Author(s):  
Rodrigo Rollin-Pinheiro ◽  
Luana Pereira Borba-Santos ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Yuri de Castro-Almeida ◽  
Victor Pereira Rochetti ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Positive Interactions ◽  
Immunocompromised Patients ◽  
Planktonic Cells ◽  
Morphological Alterations ◽  
Susceptibility Tests ◽  
Therapeutic Alternatives ◽  
Scanning Electron

Fungal infections have been increasing during the last decades. Scedosporium and Lomentospora species are filamentous fungi most associated to those infections, especially in immunocompromised patients. Considering the limited options of treatment and the emergence of resistant isolates, an increasing concern motivates the development of new therapeutic alternatives. In this context, the present study screened the Pathogen Box library to identify compounds with antifungal activity against Scedosporium and Lomentospora. Using antifungal susceptibility tests, biofilm analysis, scanning electron microscopy (SEM), and synergism assay, auranofin and iodoquinol were found to present promising repurposing applications. Both compounds were active against different Scedosporium and Lomentospora, including planktonic cells and biofilm. SEM revealed morphological alterations and synergism analysis showed that both drugs present positive interactions with voriconazole, fluconazole, and caspofungin. These data suggest that auranofin and iodoquinol are promising compounds to be studied as repurposing approaches against scedosporiosis and lomentosporiosis.

scholarly journals In Vitro Antifungal Susceptibility Of Griseofulvin, Fluconazole, Itraconazole And Terbinafine Against Clinical Isolates Of Trichophyton Rubrum And Trichophyton Mentagrophytes

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
K R Reddy ◽  
S Ram Reddy
Keyword(s):  
Trichophyton Rubrum ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Drug Susceptibility ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
National Committee ◽  
In Vitro Antifungal Susceptibility

Investigations on antifungal drug susceptibility were carried out on 90 clinical isolates of Trichophyton rubrum, and Trichophyton mentagrophytes with four antifungal drugs, namely griseofulvin, fluconazole, itraconazole and terbinafine as suggested by National Committee for Clinical Laboratory Standards (NCCLS) M27–A (1997) document by broth macrodilution method to standardize in vitro antifungal susceptibility testing and to find out the Minimum Inhibitory Concentration (MIC) of the drugs. In this study, terbinafine was found to be the most efficient drug for all isolates. Terbinafine had the lowest MIC range of 0.001 g/ml to 0.09 g/ml and MIC50 was low at 0.005 g/ml and MIC90 was also low at 0.04 g/ml against T.rubrum; and MIC range of 0.001μg/ml to 0.19μg/ml with a MIC50 of 0.01μg/ml and MIC90 at 0.09μg/ml against T.mentagrophytes. Itraconazole showed antifungal activity superior to that of fluconazole, with a MIC range of 0.04g/ml to 1.56g/ml, with MIC50 at 0.19μg/ml and MIC90 at 1.56g/ml against T.rubrum; and MIC range of 0.04μg/ml to 1.56μg/ml, with MIC50 at 0.19μg/ml and MIC90 at 0.78μg/ml against T.mentagrophytes. Griseofulvin appears to be still a potent drug for management of dermatophytoses. Griseofulvin had a MIC range of 0.15g/ml to 5.07 g/ml with MIC50 at1.26 g/ml and MIC90 at 2.53 g/ml against T.rubrum; and MIC range of 0.31μg/ml to 5.07μg/ml with MIC50 at 1.26μg/ml and MIC90 at 2.53μg/ml against T.mentagrophytes. Fluconazole showed a high MIC range of 0.19 g/ml to 50 g/ml and MIC50 was high at 1.56g/ml and MIC90 was also high at 12.5 g/ml against T.rubrum; and a high MIC range of 0.09μg/ml to 25.0μg/ml, with MIC50 at 1.56μg/ml and MIC90 at 12.5μg/ml towards T.mentagrophytes. The technique was found to be easy to perform and reliable with consistent results.

scholarly journals Real World Analysis of Response Rate and Efficacy of Oral Ketoconazole in Patients with Recalcitrant Tinea Corporis and Cruris

2021 ◽  
Author(s):  
Pooja Arora ◽  
Kabir Sardana ◽  
Anita Kulhari ◽  
Ravinder Kaur ◽  
Deepti Rawat ◽  
...  
Keyword(s):  
Response Rate ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Predisposing Factors ◽  
Antifungal Drugs ◽  
Tinea Corporis ◽  
Response To Treatment ◽  
Percentage Improvement ◽  
Alternative Drug ◽  
Susceptibility Tests

Recalcitrant dermatophytosis has had an alarming rise in India with concomitant decreased effectiveness of conventional antifungal agents. This has prompted the use of second-line agents for treatment. In this retrospective study, we aimed to analyze the response rate, efficacy, relapse rate, and side effects of oral ketoconazole (KZ) in the treatment of recalcitrant tinea corporis and cruris. Institutional records were reviewed for patients presenting with tinea cruris or corporis who had failed treatment with conventional antifungal drugs and treated with oral KZ. Potassium hydroxide (KOH) findings, culture reports, and response to treatment was noted based on the percentage improvement in lesions and reduction in itching compared with baseline. Fourty-three patients (mean age 31.3 years) with tinea corporis/cruris who had taken prior treatment with antifungals were recruited in the study. KOH mount and culture were positive in 76.7% patients. Trichophyton mentagrophytes was the commonest species, isolated in 62.8% of patients. Ketoconazole showed the lowest minimum inhibitory concentration on antifungal susceptibility tests with various antifungals. With a dose of 400 mg daily, 67.4% of patients were cured of disease with mean duration of 9.4 weeks. Patients having less than 40% clearance at 2 weeks had a 68.9% less probability of getting cured of disease. Of the 29 patients cured, 37.9% relapsed because of various predisposing factors. Two patients developed increase in liver enzymes on treatment. Our analysis suggests that KZ can be used as alternative drug in cases with failure to conventional antifungal drugs. Though there are relapses, these can be partially explained by various predisposing factors that support fungal survival and transmission.

In vitro antifungal susceptibility of griseofulvin, fluconazole, itraconazole and terbinafine against clinical isolates of Trichophyton rubrum and Trichophyton mentagrophytes

2014 ◽  
Vol 1 (4) ◽  
pp. 26-28
Author(s):  
KR Reddy ◽  
SR Reddy
Keyword(s):  
Trichophyton Rubrum ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Drug Susceptibility ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
National Committee ◽  
In Vitro Antifungal Susceptibility

Investigations on antifungal drug susceptibility were carried out on 90 clinical isolates of Trichophyton rubrum, and Trichophyton mentagrophytes with four antifungal drugs, namely griseofulvin, fluconazole, itraconazole and terbinafine as suggested by National Committee for Clinical Laboratory Standards (NCCLS) M27A (1997) document by broth macrodilution method to standardize in vitro antifungal susceptibility testing and to find out the Minimum Inhibitory Concentration (MIC) of the drugs. In this study, terbinafine was found to be the most efficient drug for all isolates. Terbinafine had the lowest MIC range of 0.001 g/mlto 0.09 g/ml and MIC50 was low at 0.005 g/ml and MIC90 was also low at 0.04 g/ml against T. rubrum; and MIC range of 0.001pg/ml to 0.19pg/ml with a MIC50 of 0.01pg/ml and MIC90 at 0.09 pg/ml against T. mentagrophytes. Itraconazole showed antifungal activity superior to that of fluconazole, with a MIC range of 0.04g/ml to l.56g/ml, with MIC50 at 0.19pg/m land MIC90 at l.56g/ml against T. rubrum; and MIC range of 0.04.g/ml to 1.56pg/ml, with MIC50 at 0.19pg/ml and MIC90 at 0.78pg/ml against T. mentagrophytes. Griseofulvin appears to be still a potent drug for management of dermatophytoses. Griseofulvin had a MIC range of 0.15g/ml to 5.07 g/ml with MIC50 at l.26 g/ml and MIC90 at 2.53 g/ml against T. rubrum; and MIC range of 0.31pg/ml to 5.07pg/ml with MIC50 at 1.26pg/ml and MIC90 at 2.53pg/ml against T. mentagrophytes. Fluconazole showed a high MIC range of 0.19 g/ml to 50 g/ml and MIC50 was high at 1.56g/ml and MIC90 was also high at 12.5 g/ml against T. rubrum; and a high MIC range of 0.09pg/ml to 25.0pg/ml, with MIC50 at 1.56pg/ml and MIC90 at 12.5pg/ml towards T. mentagrophytes. The technique was found to be easy to perform and reliable with consistent results.DOI: http://dx.doi.org/10.3126/jucms.v1i4.9569 Journal of Universal College of Medical Sciences (2013) Vol.1 No.04: 26-28

scholarly journals Population differentiation, antifungal susceptibility, and host range of Trichophyton mentagrophytes isolates causing recalcitrant infections in humans and animals

2020 ◽  
Vol 39 (11) ◽  
pp. 2099-2113
Author(s):  
Sebastian Gnat ◽  
Dominik Łagowski ◽  
Aneta Nowakiewicz ◽  
Marcelina Osińska ◽  
Łukasz Kopiński
Keyword(s):  
Host Range ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Drugs ◽  
Genomic Diversity ◽  
Clinical Isolates ◽  
Chemical Groups

Abstract The major problems in determining the causative factors of the high prevalence of dermatophytoses include the lack of a well-standardized antifungal susceptibility testing method, the low consistency of in vitro and clinical minimal inhibitory concentration values, the high genomic diversity of the population, and the unclear mechanism of pathogenicity. These factors are of particular importance when the disease is recalcitrant and relapses. Herein, we identified and characterized Trichophyton mentagrophytes isolates obtained from therapy-resistant cases in humans and animals. We used genomic diversity analysis of 17 human and 27 animal clinical isolates with the MP-PCR technique, determined their phenotypic enzymatic activity and host range, and performed antifungal susceptibility testing to currently available antifungal drugs from various chemical groups. Genomic diversity values of 35.3% and 33.3% were obtained for clinical isolates from humans and animals, respectively, yet without any relationship to the host species or antifungal drug to which resistance in therapy was revealed. The highest activity of keratinase enzymes was recorded for fox, guinea pig, and human hairs. These hosts can be considered as the main species in the host range of these isolates. A phenyl morpholine derivative, i.e. amorolfine, exhibited superior activity against strains obtained from both humans and animals with the lowest MIC50. Interestingly, high compliance of terbinafine in vitro resistance with clinical problems in the treatment with this substance was shown as well. The high resistance of dermatophytes to drugs is the main cause of the recalcitrance of the infection, whereas the other features of the fungus are less important.

A study on the antifungal susceptibility pattern of dermatophytes isolated in a tertiary care hospital

2017 ◽  
Vol 6 (05) ◽  
pp. 5379
Author(s):  
Vanathi Sabtharishi* ◽  
Radhika Katragadda ◽  
Thyagarajan Ravinder
Keyword(s):  
Tertiary Care Hospital ◽  
Antifungal Susceptibility ◽  
Tertiary Care ◽  
Antifungal Drugs ◽  
Dilution Method ◽  
Care Hospital ◽  
Susceptibility Pattern ◽  
Superficial Mycosis ◽  
Broth Dilution ◽  
Common Infections

Recent years, due to increased usage of antifungal treatment worldwide, there is an increased chance of rising resistance among antifungal drugs too. Dermatophytic infections causes’ superficial mycosis and it affects skin, hair and nail. These infections are more common and antifungal drugs are used everywhere to treat those common infections. To conduct a study by determining the antifungal susceptibility pattern in dermatophytic isolates from patients attending dermatology OPD in a tertiary care hospital. A total of 217 samples like hair, nail and skin scrapings were obtained and isolation of dermatophytes was done. Antifungal susceptibility testing for dermatophytes was performed by micro broth dilution method. Antifungal drugs tested were Griseofulvin, Fluconazole, Itraconazole and Ketoconazole. Minimum inhibitory concentration for each drug for fungal isolates was tested and results studied. Fluconazole showed a higher MIC values in the range of 1-8µg/ml. Itraconazole showed the lowest MIC values by micro broth dilution method. Since there is limitation of standard guidelines and protocol, meticulous research must be conducted on effect of antifungals and derive at universally implementable guidelines.

scholarly journals Spectrum and theIn VitroAntifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Birhan Moges ◽  
Adane Bitew ◽  
Aster Shewaamare
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Assay Method ◽  
Cryptococcus Laurentii ◽  
Susceptibility Pattern ◽  
Test Procedures ◽  
Disk Diffusion Assay ◽  
Diffusion Assay

Background.In Ethiopia, little is known regarding the distribution and thein vitroantifungal susceptibility profile of yeasts.Objective.This study was undertaken to determine the spectrum and thein vitroantifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC.Method.Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method.Result.One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART.C. albicanswas the most frequently isolated species followed byC. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorulaspecies. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively.Conclusion.Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs.

scholarly journals Recent Exposure to Caspofungin or Fluconazole Influences the Epidemiology of Candidemia: a Prospective Multicenter Study Involving 2,441 Patients

2010 ◽  
Vol 55 (2) ◽  
pp. 532-538 ◽  
Author(s):  
Olivier Lortholary ◽  
Marie Desnos-Ollivier ◽  
Karine Sitbon ◽  
Arnaud Fontanet ◽  
Stéphane Bretagne ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Odds Ratio ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Antifungal Drugs ◽  
Surveillance Program ◽  
Prospective Multicenter Study ◽  
Recent Exposure ◽  
Adults And Children

ABSTRACTA prospective multicenter surveillance program on yeast bloodstream infections was implemented in the Paris, France, area without restrictions on ward of hospitalization (intensive care unit, hematology, and surgery) or age (adults and children). The present analysis concerns 2,618 isolates collected over 7 years from 2,441 patients. Centralized species identification and antifungal susceptibility testing using the EUCAST methodology were performed. Almost 10% (232/2,441) of the patients had recently (≤30 days) been treated with antifungal drugs. We analyzed the effect of recent exposure to fluconazole (n= 159) or caspofungin (n= 61) on the proportions of the five majorCandidaspecies. For both drugs, preexposure was associated with a decreased prevalence ofCandida albicansin favor of less drug-susceptible species (C. glabrataandC. kruseifor the former andC. parapsilosisand, to a lesser extent,C. glabrataandC. kruseifor the latter;P= 0.001). In the multivariate analysis, the risk of being infected with an isolate with decreased susceptibility to fluconazole was independently associated with an age of ≥15 years (odds ratio [OR] = 2.45; 95% confidence interval [CI] = 1.39 to 4.31;P= 0.002) and with recent exposure to fluconazole (OR = 2.17; 95% CI = 1.51 to 3.13;P< 0.001), while the risk of being infected with an isolate with decreased susceptibility to caspofungin was independently associated with an age <15 years (OR = 2.53; 95% CI = 1.43 to 4.48;P= 0.001) and with recent exposure to caspofungin (OR = 4.79; 95% CI = 2.47 to 9.28;P< 0.001). These findings could influence future recommendations for the management of candidemia.

GROWTH INHIBITORY ACTIVITIES OF THE RHIZOME CRUDE EXTRACT OF Curcuma longa ON THE HUMAN PATHOGENIC FUNGUS Mucor circinelloides

2020 ◽  
Vol 65 (10) ◽  
pp. 82-91
Author(s):  
Phuong Nguyen Anh ◽  
Mai Le Thi Tuyet ◽  
Trung Trieu Anh
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Fungal Infections ◽  
Early Stage ◽  
Curcuma Longa ◽  
Pathogenic Fungus ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Dilution Method

Mucormycosis is an uncommon but life-threatening invasive fungal infection, mostly occurs in immunocompromised patients. Lacking the appropriate antifungal drugs is one of the reasons that lead to difficulties in the management of mucormycosis. Curcuma longa has been used traditionally and widely to treat various diseases, including fungal infections. In the search for novel antifungal compounds from natural resources, we evaluated the effect of rhizome crude extract of C. longa on Mucor circinelloides – a causal agent of mucormycosis. The results of screening, using broth dilution method and agar-well diffusion method, showed that the C. longa extract exhibited promising antifungal activity against the fungus M. circinelloides. In liquid medium, C. longa extract decreased the ability of spore germination and the speed of hyphae formation of M. circinelloides decreased by up to approximately 70% and 90%, respectively. Besides, in a solid medium, the crude extract presented similar activity with amphotericin B (400 μg\mL) in decreasing the growth of M. circinelloides by nearly 77%. Moreover, the extract of C. longa also likely to induce the yeast-like type of growth of the dimorphic M. circinelloides in the early stage. These results suggest the plant could be a potential source for further study on biochemical components and the mechanism of its antifungal activity.

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

2016 ◽  
Vol 7 (1) ◽  
pp. 11
Author(s):  
Sultana Razia ◽  
Shahida Anwar ◽  
Md. Ruhul Amin Miah ◽  
Najmun Nahar ◽  
Ripon Barua
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Test Method ◽  
Susceptibility Test ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Antifungal Susceptibility Test ◽  
Mic Value

<p><strong>Background:</strong> 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.<strong> </strong></p><p><strong>Objective:</strong> The study was undertaken to perform a simple screening drug susceptibility test of T. rnbrum by Semi Solid Agar Antifungal Susceptibility (SAAS) <strong></strong></p><p><strong>Method:</strong> 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. <strong></strong></p><p><strong>Results:</strong> 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 &gt;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 &gt;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. <strong></strong></p><p><strong>Conclusion:</strong> 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.</p>

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