Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates

2019 ◽  
Vol 14 (17) ◽  
pp. 1477-1488 ◽  
Author(s):  
Lívia G do AV Sá ◽  
Cecília R da Silva ◽  
Rosana de S Campos ◽  
João B de A Neto ◽  
Letícia S Sampaio ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Candida Spp ◽  
Flow Cytometric ◽  
Fluconazole Resistant ◽  
Anticandidal Activity ◽  
Checkerboard Assay ◽  
Resistant Strains ◽  
Radical Generation

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.

scholarly journals Synergistic Antifungal Activity of Chitosan with Fluconazole against Candida albicans, Candida tropicalis, and Fluconazole-Resistant Strains

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5114
Author(s):  
Wei-Hsuan Lo ◽  
Fu-Sheng Deng ◽  
Chih-Jung Chang ◽  
Ching-Hsuan Lin
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Candida Tropicalis ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Combinational Treatment ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

(1) Background: Few antifungal drugs are currently available, and drug-resistant strains have rapidly emerged. Thus, the aim of this study is to evaluate the effectiveness of the antifungal activity from a combinational treatment of chitosan with a clinical antifungal drug on Candida albicans and Candida tropicalis. (2) Methods: Minimum inhibitory concentration (MIC) tests, checkerboard assays, and disc assays were employed to determine the inhibitory effect of chitosan with or without other antifungal drugs on C. albicans and C. tropicalis. (3) Results: Treatment with chitosan in combination with fluconazole showed a great synergistic fungicidal effect against C. albicans and C. tropicalis, but an indifferent effect on antifungal activity when challenged with chitosan-amphotericin B or chitosan-caspofungin simultaneously. Furthermore, the combination of chitosan and fluconazole was effective against drug-resistant strains. (4) Conclusions: These findings provide strong evidence that chitosan in combination with fluconazole is a promising therapy against two Candida species and its drug-resistant strains.

scholarly journals Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Pitchayaphong Keereedach ◽  
Karnjana Hrimpeng ◽  
Khaemaporn Boonbumrung
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Efflux Pump ◽  
Clinical Problem ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
Common Mechanism ◽  
Fluconazole Resistant ◽  
Resistant Strains

Candidiasis caused by the fluconazole-resistant opportunistic pathogen Candida albicans is an intractable clinical problem that threatens immunocompromised or normal individuals. The most common mechanism of fluconazole resistance in C. albicans is the failure of cells to accumulate the drug due to increased expression of the efflux proteins encoded by the CDR1, CDR2, and MDR1 genes. Because the number of current antifungal drugs is limited, it is necessary to develop new therapeutic strategies. This study aimed to evaluate the antifungal activity of Thai Cajuput oil, its synergism with fluconazole, and its effect on efflux-pump gene expression in fluconazole-resistant C. albicans clinical isolates. Thus, we first detected the efflux-pump genes in fourteen resistant strains by PCR. The frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively, and these efflux-pump genes were distributed in three distinct patterns. Subsequently, the antifungal activity of Thai Cajuput oil was assessed by broth macrodilution and its synergism with fluconazole was evaluated by the checkerboard assay. The changes in the expression levels of CDR1, CDR2, and MDR1 after treatment with Thai Cajuput oil were analyzed by qRT-PCR. The MICs and MFCs of Thai Cajuput oil ranged from 0.31 to 1.25 μl/ml and 0.63 to 1.25 μl/ml, respectively, and its activity was defined as fungicidal activity. The MICs of the combination of Thai Cajuput oil and fluconazole were much lower than the MICs of the individual drugs. Interestingly, sub-MICs of Thai Cajuput oil significantly reduced the MDR1 expression level in resistant strains P < 0.05 . Our study suggests that Thai Cajuput oil can be used to create new potential combination therapies to combat the antifungal resistance of C. albicans.

Evaluation of the antifungal activity in vitro of midazolam against fluconazole-resistant Candida spp. isolates

2021 ◽  
Vol 16 (2) ◽  
pp. 71-81
Author(s):  
Maria AV Holanda ◽  
Cecília R da Silva ◽  
João B de A Neto ◽  
Lívia G do AV Sá ◽  
Francisca BSA do Nascimento ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Probable Mechanism ◽  
Cytotoxicity Test ◽  
Broth Microdilution ◽  
Planktonic Cells ◽  
Candida Spp ◽  
Antifungal Potential ◽  
Fluconazole Resistant ◽  
Scanning Electron

Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125–250 μg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 μg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.

scholarly journals Design, Synthesis and Anticandidal Evaluation of Indazole and Pyrazole Derivatives

2021 ◽  
Vol 14 (3) ◽  
pp. 176
Author(s):  
Karen Rodríguez-Villar ◽  
Alicia Hernández-Campos ◽  
Lilián Yépez-Mulia ◽  
Teresita del Rosario Sainz-Espuñes ◽  
Olivia Soria-Arteche ◽  
...  
Keyword(s):  
Bloodstream Infections ◽  
Antifungal Drugs ◽  
Pyrazole Derivatives ◽  
Design Synthesis ◽  
Bioisosteric Replacement ◽  
Current Therapies ◽  
Anticandidal Activity ◽  
Resistant Strains ◽  
A Priority

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against C. albicans, C. glabrata, and C. tropicalis strains. The series of 3-phenyl-1H-indazole moiety (10a–i) demonstrated to have the best broad anticandidal activity. Particularly, compound 10g, with N,N-diethylcarboxamide substituent, was the most active against C. albicans and both miconazole susceptible and resistant C. glabrata species. Therefore, the 3-phenyl-1H-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype.

scholarly journals Antifungal Properties of Crude Extracts, Fractions, and Purified Compounds from Bark ofCuratella americanaL. (Dilleniaceae) againstCandidaSpecies

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Cleyton Eduardo Mendes de Toledo ◽  
Patrícia Regina Santos ◽  
João Carlos Palazzo de Mello ◽  
Benedito Prado Dias Filho ◽  
Celso Vataru Nakamura ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Virulence Factors ◽  
Crude Extract ◽  
Ethyl Acetate Fraction ◽  
Yeast Culture ◽  
Ethnomedicinal Plant ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Preliminary Study ◽  
Curatella Americana

The ethnomedicinal plantCuratella americanaL. (Dilleniaceae) is a common shrub in the Brazilian cerrado, in which crude extract showed antifungal activity in a preliminary study. In this work, the antifungal and cytotoxic properties of the crude extract, fractions, and isolated compounds fromC. americanawere evaluated against the standard yeast strainsCandida albicans,C. tropicalis, andC. parapsilosis, clinical isolates, and fluconazole-resistant strains. The combinatory effects between subfractions and isolated compounds and effects on cell morphology, virulence factors, and exogenous ergosterol were also evaluated. The MIC obtained against theCandidaspecies including fluconazole-resistant strain ranged from 15.3 to 31.3 µg/mL for crude extract, 3.9 to 15.6 µg/mL for ethyl acetate fraction, and 7.8 to 31.3 µg/mL for subfractions. The isolated compounds identified as 4′-O-methyl-catechin, epicatechin-3-O-gallate, and 4′-O-methyl-catechin-3-O-gallate showed lower antifungal activity than the crude extract and fractions (MIC ranging from 31.3 to 125.0 µg/mL). The addition of exogenous ergosterol to yeast culture did not interfere in the antifungal activity of the extract and its fractions. Synergistic antifungal activity was observed between subfractions and isolated compounds. The effects on virulence factors and the different mechanisms of action compared to fluconazole and nystatin suggest that this ethnomedicinal plant may be an effective alternative treatment for candidiasis.

scholarly journals Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

2020 ◽  
Vol 69 (6) ◽  
pp. 830-837
Author(s):  
Raimunda Sâmia Nogueira Brilhante ◽  
José Alexandre Telmos Silva ◽  
Géssica dos Santos Araújo ◽  
Vandbergue Santos Pereira ◽  
Wilker Jose Perez Gotay ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
Species Complex ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Species Activity ◽  
Checkerboard Assay

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

scholarly journals In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

1998 ◽  
Vol 42 (10) ◽  
pp. 2503-2510 ◽  
Author(s):  
Maurizio Del Poeta ◽  
Wiley A. Schell ◽  
Christine C. Dykstra ◽  
Susan K. Jones ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Inhibitory Compounds ◽  
Wide Range ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

Green synthesis and antifungal activity of Al2O3NPs against fluconazole-resistant Candida spp isolated from a tertiary care hospital

RSC Advances ◽  
2016 ◽  
Vol 6 (109) ◽  
pp. 107577-107590 ◽  
Author(s):  
Mohammad Jalal ◽  
Mohammad Azam Ansari ◽  
Arun Kumar Shukla ◽  
Syed G. Ali ◽  
Haris M. Khan ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Green Synthesis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Care Hospital ◽  
Candida Spp ◽  
Fluconazole Resistant

Antifungal activity of ecofriendly and cost effectively prepared Al2O3NPs onCandia alibicans.

scholarly journals Antifungal Activity of Extracts, Fractions, and Constituents from Coccoloba cowellii Leaves

2021 ◽  
Vol 14 (9) ◽  
pp. 917
Author(s):  
Daniel Méndez ◽  
Julio C. Escalona-Arranz ◽  
Enrique Molina Pérez ◽  
Kenn Foubert ◽  
An Matheeussen ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Methanolic Extract ◽  
Preliminary Investigation ◽  
Planktonic Cells ◽  
Candida Spp ◽  
Resazurin Assay ◽  
Bioassay Guided Fractionation ◽  
Trimethyl Ether ◽  
In Vitro Antifungal Activity

Coccoloba cowellii Britton (Polygonaceae, order Caryophyllales) is an endemic and critically endangered plant species that only grows in the municipality of Camagüey, a province of Cuba. A preliminary investigation of its total methanolic extract led to the discovery of promising antifungal activity. In this study, a bioassay-guided fractionation allowed the isolation of quercetin and four methoxyflavonoids: 3-O-methylquercetin, myricetin 3,3′,4′-trimethyl ether, 6-methoxymyricetin 3,4′-dimethyl ether, and 6-methoxymyricetin 3,3′,4′-trimethyl ether. The leaf extract, fractions, and compounds were tested against various fungi and showed strong in vitro antifungal activity against Cryptococcus neoformans and various Candida spp. with no cytotoxicity (CC50 > 64.0 µg/mL) on MRC-5 SV2 cells, determined by a resazurin assay. A Candida albicans SC5314 antibiofilm assay indicated that the antifungal activity of C. cowellii extracts and constituents is mainly targeted to planktonic cells. The total methanolic extract showed higher and broader activity compared with the fractions and mixture of compounds.

scholarly journals Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.

2021 ◽  
Vol 12 ◽  
Author(s):  
Renato Dantas-Medeiros ◽  
Ana Caroline Zanatta ◽  
Luanda Bárbara Ferreira Canário de Souza ◽  
Júlia Morais Fernandes ◽  
Bruno Amorim-Carmo ◽  
...  
Keyword(s):  
Scientific Evidence ◽  
Human Erythrocytes ◽  
Antibiofilm Activity ◽  
Phytochemical Analysis ◽  
Candida Spp ◽  
Vaginal Infections ◽  
Biofilm Inhibition ◽  
Butanol Fraction ◽  
Fluconazole Resistant ◽  
Resistant Strains

Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.

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