scholarly journals Biofabricated Silver Nanoparticles Synergistically Activate Amphotericin B Against Mature Biofilm Forms of Candida Albicans

2017 ◽  
Vol 4 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Shivkrupa D. Halbandge ◽  
Supriya P. Mortale ◽  
Sankunny Mohan Karuppayil
Keyword(s):  
Silver Nanoparticles ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Hemolytic Activity ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Fractional Inhibitory Concentration ◽  
Planktonic Growth ◽  
Concentration Indices

Background: Biofilm formation by Candida albicans is a significant clinical challenge. Fungal biofilms are resistant to most of the currently available antifungal agents. Amphotericin-B (AmB) is an antifungal agent used for the treatment of systematic fungal infections but it is well known for its toxicities and side-effects. Novel approaches are needed to treat these infections that can reduce its toxicities. Objectives: Current study aims to evaluate the efficacy of silver nanoparticles (SNPs) alone and in combination with AmB against growth and biofilm formation in C. albicans. Methods: Combinations of SNP-AmB were tested against planktonic growth and biofilm formation in vitro. Micro broth dilution method was used to study planktonic growth and biofilm formation. The fractional inhibitory concentration indices (FICI) were calculated by using a checkerboard format. Biofilm formation was analyzed by using XTT-metabolic assay. Results: MIC of AmB for developing biofilm was lowered by 16 fold in combination with SNPs. The calculated fractional inhibitory concentration indices were 0.1875 suggesting that this interaction is synergistic. Similarly, the mature biofilms were significantly prevented by SNPs-AmB combination. This interaction was synergistic. Furthermore, interaction between SNPs and AmB against planktonic growth was additive. Hemolytic activity assay was carried out on these drugs and combinations. Drug required for inhibition alone as well as in combination did not exhibit hemolytic activity. Conclusion: The combinations with SNPs lead to decreases in the dosage of AmB required for anti-Candida activity. SNPs-AmB combination could be an effective strategy against biofilm formed by C. albicans.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals Multilaboratory Testing of Antifungal Drug Combinations against Candida Species and Aspergillus fumigatus: Utility of 100 Percent Inhibition as the Endpoint

2014 ◽  
Vol 59 (3) ◽  
pp. 1759-1766 ◽  
Author(s):  
Ping Ren ◽  
Ming Luo ◽  
Shao Lin ◽  
Mahmoud A. Ghannoum ◽  
Nancy Isham ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Drug Interactions ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Candida Species ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Content Type ◽  
Drug Antagonism ◽  
Concentration Indices

ABSTRACTFour laboratories tested three isolates ofCandidaspecies and two isolates ofAspergillus fumigatususing 96-well plates containing combinations of amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. The majority of summation fractional inhibitory concentration indices (ΣFICI) based on the Lowe additivity formula suggested indifferent drug interactions (ΣFICI > 0.5 and ≤4.0) and no instance of drug antagonism (ΣFICI > 4.0). The intra- and interlaboratory agreement rates were superior when MIC100readings were used as endpoints (at a 99% confidence interval [CI]).

scholarly journals Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

2014 ◽  
Vol 59 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Kaat De Cremer ◽  
Ellen Lanckacker ◽  
Tanne L. Cools ◽  
Marijke Bax ◽  
Katrijn De Brucker ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Drug Repositioning ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Structural Homologues ◽  
Increased Activity ◽  
Candida Albicans Biofilms ◽  
Concentration Indices

ABSTRACTMucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole againstCandida albicansbiofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affectingC. albicansbiofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treatC. albicansbiofilm-related infections.

scholarly journals Synergy of Nitric Oxide and Azoles againstCandida Species In Vitro

1998 ◽  
Vol 42 (9) ◽  
pp. 2342-2346 ◽  
Author(s):  
Gail E. McElhaney-Feser ◽  
Robert E. Raulli ◽  
Ronald L. Cihlar
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Half Life ◽  
Inhibitory Concentration ◽  
Therapeutic Strategies ◽  
Fractional Inhibitory Concentration ◽  
Concentration Indices

ABSTRACT The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was active against six species of Candida for which the MICs necessary to inhibit 50% growth (MIC50s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. kruseiwere the most susceptible to the compound. In addition to a determination of NO effects alone, the complex was utilized to investigate the synergistic potential of released NO in combination with ketoconazole, fluconazole, and miconazole. Activity was investigated in vitro against representative strains of Candida albicans, C. krusei, C. parapsilosis,C. tropicalis, C. glabrata, and C. dubliniensis. Determination of MIC50, MIC80 and MICs indicated that DETA-NO inhibits all strains tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of DETA-NO with each azole was synergistic against all strains tested as measured by fractional inhibitory concentration indices that ranged from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with similar properties may be useful in the development of new therapeutic strategies for treatment of Candida infections.

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

scholarly journals In vitro activities of Traganum nudatum and Mentha pulegium extracts combined with amphotericin B against Candida albicans in production of hydrolytic enzymes

2020 ◽  
Author(s):  
Ikram Tefiani ◽  
Sidi Mohammed Lahbib Seddiki ◽  
Moustafa Yassine Mahdad
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Culture Media ◽  
Hydrolytic Enzymes ◽  
Normal Flora ◽  
Mentha Pulegium ◽  
Hydrolytic Activities

Background and Purpose: Candida albicans is an important microorganism in the normal flora of a healthy subject; however, it has an expedient pathogenic character that induces hydrolytic virulence. Regarding this, the present study aimed to find an in vitro alternative that could reduce the virulence of this yeast. Materials and Methods: For the purpose of the study, the effect of amphotericin B (AmB) combined with the extract of Traganum nudatum (E1) or Mentha pulegium (E2) was evaluated against the hydrolytic activities of esterase, protease, and phospholipase. This effect was determined by calculating the minimum inhibitory concentration (MIC), used to adjust the extract/AmB mixtures in culture media. Results: The evaluated Pz values, which corresponded to the different enzymatic activities, showed a decrease in the hydrolytic activities of C. albicans strains after the addition of E1/AmB and E2/AmB combinations at descending concentrations (lower than the obtained MICs). Conclusion: Based on the findings, it would be possible to reduce the pathogenesis of this species without destabilizing the balance of the flora.

scholarly journals Activities of Three Quinolones, Alone and in Combination with Extended-Spectrum Cephalosporins or Gentamicin, against Stenotrophomonas maltophilia

1998 ◽  
Vol 42 (8) ◽  
pp. 2002-2005 ◽  
Author(s):  
Melissa A. Visalli ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Active Compound ◽  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Determination Method ◽  
Extended Spectrum ◽  
Time Kill ◽  
Synergy Testing ◽  
Checkerboard Titration ◽  
Concentration Indices

The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains. The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 μg/ml; levofloxacin, 2.0 and 4.0 μg/ml; ciprofloxacin, 4.0 and 16.0 μg/ml; cefoperazone, >128.0 and >128.0 μg/ml; ceftazidime, 32.0 and >128.0 μg/ml; cefpirome, >128.0 and >128.0 μg/ml; and gentamicin, 128.0 and >128.0 μg/ml. Synergistic fractional inhibitory concentration indices (≤0.5) were found for ≥50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains. For 20 strains tested by the checkerboard titration and time-kill methods, synergy (≥100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h. At 12 h, trovafloxacin at 0.004 to 0.5 μg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains. Levofloxacin at 0.03 to 0.5 μg/ml and ciprofloxacin at 0.5 to 2.0 μg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively. Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations.

scholarly journals The The Effects of Cinnamaldehyde (Cinnamon Derivatives) and Nystatin on Candida Albicans and Candida Glabrata

2019 ◽  
Vol 7 (7) ◽  
pp. 1067-1070 ◽  
Author(s):  
Sedigheh Bakhtiari ◽  
Soudeh Jafari ◽  
Jamileh Bigom Taheri ◽  
Tahereh Sadat Jafarzadeh Kashi ◽  
Zahra Namazi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Candida Species ◽  
Candida Glabrata ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Minimum Fungicidal Concentration ◽  
Microdilution Method

BACKGROUND: Candida species are the most common opportunistic fungal infections. Today, cinnamon plants have been considered for anti-Candida properties. AIM: This study aimed to investigate the effectiveness of cinnamaldehyde extract (from cinnamon derivatives) on Candida albicans and Candida glabrata species and comparison with nystatin. MATERIAL AND METHODS: In this study, cinnamaldehyde and nystatin were used. The specimens included Candida albicans and Candida glabrata. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured for each one by the microdilution method. This experiment was repeated three times. RESULTS: Cinnamaldehyde extract at a concentration of 62.5 μl/ml was able to prevent the growth of Candida albicans, at a concentration of 93.7 μl/ml, causing Candida albicans to disappear, at 48.8 μl/ml, to prevent the growth of Candida glabrata, and in the concentration of 62.5 μl/ml, causes the loss of Candida glabrata. In comparison, nystatin at 0.5 μg/ml concentration prevented the growth of Candida albicans, at concentrations of 1 μg/ml causing Candida albicans to be destroyed, at 4 μg/ml concentration to prevent the growth of Candida glabrata, and at a concentration of 8 μg/ml causes the loss of Candida glabrata. The results were the same every three times. CONCLUSIONS: Although cinnamaldehyde extract had an effect on fungal growth in both Candida albicans and Candida glabrata with a fatal effect; the effect on these two species was lower than nystatin.

Effect of antifungals on itraconazole resistant Candida glabrata

2010 ◽  
Vol 5 (3) ◽  
pp. 318-323 ◽  
Author(s):  
Soňa Kucharíková ◽  
Patrick Dijck ◽  
Magdaléna Lisalová ◽  
Helena Bujdáková
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Low Concentrations ◽  
Reduction Assay ◽  
Very High

AbstractIn the last decade, infections caused by Candida glabrata have become more serious, particularly due to its decreased susceptibility to azole derivatives and its ability to form biofilm. Here we studied the resistance profile of 42 C. glabrata clinical isolates to different azoles, amphotericin B and echinocandins. This work was also focused on the ability to form biofilm which plays a role in the development of antifungal resistance. The minimal inhibitory concentration testing to antifungal agents was performed according to the CLSI (Clinical and Laboratory Standards Institute) M27-A3 protocol. Quantification of biofilm was done by XTT reduction assay. All C. glabrata clinical isolates were resistant to itraconazole and sixteen also showed resistance to fluconazole. All isolates remained susceptible to voriconazole. Amphotericin B was efficient in a concentration range of 0.125–1 mg/L. The most effective antifungal agents were micafungin and caspofungin with the MIC100 values of ≤0.0313–0.125 mg/L. Low concentrations of these agents reduced biofilm formation as well. Our results show that resistance of different C. glabrata strains is azole specific and therefore a single azole resistance cannot be assumed to indicate general azole resistance. Echinocandins proved to have very high efficacy against clinical C. glabrata strains including those with ability to form biofilm.

Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

2020 ◽  
Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

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