Candida Biofilms Research Articles

Synergistic Antifungal Activity of Chito-Oligosaccharides and Commercial Antifungals on Biofilms of Clinical Candida Isolates.

The development of yeast biofilms is a major problem due to their increased antifungal resistance, which leads to persistent infections with severe clinical implications. The high antifungal activity of well-characterized chitosan polymers makes them potential alternatives for treating yeast biofilms. The activity of a chito-oligosaccharide with a depolymerization degree (DPn) of 32 (C32) and a fraction of acetylation (FA) of 0.15 on Candida sp. biofilms was studied. The results showed a concentration-dependent reduction in the number of viable cells present in C. albicans, C. glabrata, and C. guillermondii preformed biofilms in the presence of C32, especially on intermediate and mature biofilms. A significant decrease in the metabolic activity of yeast biofilms treated with C32 was also observed. The antifungals fluconazole (Flu) and miconazole (Mcz) decreased the number of viable cells in preformed early biofilms, but not in the intermediate or mature biofilms. Contrary to Flu or Mcz, C32 also reduced the formation of new biofilms. Interestingly, a synergistic effect on yeast biofilm was observed when C32 and Flu/Mcz were used in combination. C32 has the potential to become an alternative therapeutic agent against Candida biofilms alone or in combination with antifungal drugs and this will reduce the use of antifungals and decrease antifungal resistance.

PFM-001 - Real-time assessment of Candida biofilm formation

PFM-001 - Real-time assessment of Candida biofilm formation

The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections.

Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.

The effectiveness of surface disinfectants and a micellic H2O2 based water disinfectant on Candida auris

BackgroundAs infection control faces new challenges from emerging, multidrug resistant strains of the yeast Candida auris, this study was conducted in order to examine the efficacy of hospital surface disinfectants and a new water disinfectant against C. auris biofilm forms. MethodsWe tested four reference strains of C. auris (NCPF8971, NCPF8977, NCPF8984, DSM21092) and one C. albicans strain (ATCC10231) against disinfectants based on ethanol (ETH), quaternary ammonium (QAC), a combination of glutaraldehyde, quaternary ammonium and surfactant (ALD) and potassium peroxymonosulfate (PP) as well as 3.4% H2O2 and 4.25% H2O2 alone. In addition, a micellic-based formulation containing 17% v/v hydrogene peroxide disinfectant (mH2O2) was tested. The efficacy of the disinfectants was measured in a 96-well plate using tetrazolium salt reduction (XTT) and the log10 reduction assay. ResultsETH and QAC displayed in clinically recommended concentrations more than 5log10 reduction and more than 80% XTT activity reduction for all of the Candida biofilms and planktonic cells. Only biofilms of C. auris NCPF8984 were additionally sensitive to all remaining disinfectants. All tested C. auris biofilms were sensitive to PP disinfectant and showed more than 5log10 reduction. However, the XTT assay showed a reduction of less than 80% for the PP disinfectant, indicating the presence of active but non-culturable cells. The 25% mH2O2 (corresponding to 4.25% H2O2) killed Candida biofilms after 1 minute.

Arginine-phenylalanine and arginine-tryptophan-based surfactants as new biocompatible antifungal agents and their synergistic effect with Amphotericin B against fluconazole-resistant Candida strains

In the past two decades, the increase in microbial resistance to conventional antimicrobials has spurred scientists around the world to search tirelessly for new treatments. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds. In this work, two new cationic amino acid-based surfactants were synthesized and their physicochemical, antifungal and antibiofilm properties evaluated. The surfactants were based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM) and prepared from renewable raw materials using a simple chemical procedure. The critical micelle concentrations of the new surfactants were determined by conductivity and fluorescence. Micellization of LPAM and LTAM took place at 1.05 and 0.54 mM, respectively. Both exhibited good antifungal activity against fluconazole-resistant Candida spp. strains, with a low minimum inhibitory concentration (8.2 μg/mL). Their mechanism of action involves alterations in cell membrane permeability and mitochondrial damage, leading to death by apoptosis. Furthermore, when LPAM and LTAM were applied with Amphotericin B, a significant synergistic effect was observed against all the studied Candida strains. These new cationic surfactants are also able to disperse biofilms of Candida spp. at low concentrations. The results indicate that LPAM and LTAM have potential application to combat the advance of fungal resistance as well as microbial biofilms.

Effectiveness of antimicrobial photodynamic therapy with indocyanine green against the standard and fluconazole-resistant Candida albicans.

Antimicrobial photodynamic therapy (aPDT) is an alternative approach. The current study aimed to investigate the efficacy of aPDT with indocyanine green (ICG) against two Candida albicans (C. albicans) strains. In this in vitro study, the inoculum of standard ATCC 10,231 (S) and fluconazole-resistant (FR) strains were adjusted to the turbidity of a 0.5 McFarland standard. Each strain was allocated into 4 groups: S1 and FR1) control groups, S2 and FR2) ICG-treated groups (1µg/mL), S3 and FR3) laser-irradiated groups (wavelength: 810nm; mode: continuous-wave; output power: 300 mW; spot size: 4.5mm; exposure time: 120s; radiation dose: 228J/cm2), S4 and FR4) ICG-mediated-aPDT groups. After treatments, the number of colony-forming units per milliliter (CFU/mL) was calculated. Using the XTT reduction assay, the effects of each treatment on Candida biofilm formation were evaluated. Data were analyzed using SPSS software version 22. In both strains, the maximum number of CFUs was observed in the control group, followed by ICG-treated, laser-irradiated, and ICG-mediated-aPDT groups. In ATCC 10,231 strain, the XTT assay exhibited significant difference between ICG-mediated-aPDT and control groups (p < 0.0001). However, the ICG, laser, and ICG-mediated-aPDT groups in fluconazole-resistant strain showed significant differences when compared with the control (p < 0.05). The mean Candida CFUs and the XTT assay did not show any significant difference between the ATCC 10,231 and fluconazole-resistant strains with respect to each treatment. Data suggest ICG-mediated-aPDT could diminish Candida CFUs in laboratory; however, further studies are warranted to confirm its efficacy and safety to be applied in clinics.

Effect of Distreptaza Distrept on the specific activity of fluconazole against Candida biofilms

The ability of yeast-like fungi to form biofilms (structurally organized microbial communities) leads to chronicity of the inflammatory process and recurrent course of mycoses. Biofilms formed by the fungus Candida spp. are characterized by increased resistance to most antifungals and effectors of the immune system. Promising antibiotics are enzymes. Their specificity to the structural components of the biofilm can be used to prevent biofilm formation and destruction of the formed biofilm. The article presents the results of studying the sensitivity biofilms formed by Candida fungi to the action of the enzyme drug Distreptaza Distrept, as well as its effect on the specific antifungal activity of fluconazole.Research objective: to evaluate the Distreptaza Distrept impact on the antifungal activity of fluconazole on biofilms of Candida spp.Materials and methods. One-day cultures of C. albicans and C. glabrata were used in the experiments. To study the effect on biofilm formation Distreptaza Distrept, fluconazole solutions and microorganisms were applied simultaneously, when exposed to the formed biofilms for 24 h after application of the fungal inoculum. The experiments were carried out in accordance with conventional methods based on the sorption of gentian violet by biofilm structures with subsequent desorption of the dye in an organic solvent.Results. Experiments have shown that Distreptaza Distrept disrupts the film formation of C. glabrata, the inhibition is 85.6%. The enzyme preparation affects the biofilms formed by yeast-like fungi, biomass of C. glabrata decreases by 43.6%. It was found that Distreptaza Distrept enhances the specific antibiotic action of fluconazole at the stage of film formation against C. albicans by 13.1%, C. glabrata by 70.4%. Biomass of the one-day biofilm formed by C. glabrata is reduced by 80.2% if there was an enzyme drug and fluconazole in the incubation medium.Conclusion. Distreptaza Distrept has antibiotic biofilm activity, increases the specific antifungal effect of fluconazole on biofilms of Candida fungi. The data obtained indicate the feasibility of this drug in recurrent infections caused by yeast-like fungi, including diseases caused by azole-resistant strains of Candida spp.

8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices.

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters.Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity.Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs.Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time-kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation.Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole.Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.

Evaluation of Staphylococcus aureus and Candida albicans biofilms adherence to PEEK and titanium-alloy prosthetic spine devices.

Titanium and polyether-ether-ketone (PEEK) interbody cages are commonly used for spine fusion. Few data are known about bacterial and yeast biofilms formation in these implants. The aim of this study was to compare Staphylococcus aureus and Candida albicans biofilm formation in the surface of two different interbody devices used routinely in spine surgery. Six bodies of proof specimens of PEEK and titanium alloy were used for microbiological tests, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Experimental biofilm was produced with Staphylococcus aureus and Candida albicans, followed by quantitative analysis of planktonic cells and sessile cells. The comparison between the medians of biofilm quantification between the two models was performed using the Mann-Whitney test and considered the statistical difference for a p < 0.05. In the S. aureus model, in both planktonic and sessile cell counts, titanium-alloy samples showed lower values for colony forming units per milliliter (UFC/mL) (p < 0.05). The evaluation through the optic density of planktonic and sessile cells showed lower values in the titanium-alloy samples, however, only statistically significant in planktonic cell count (p < 0.05). The count of planktonic yeast cells in PEEK was similar to titanium-alloy samples, while the count of sessile yeast cells in titanium alloy was lower when compared to PEEK (p < 0.05). Titanium-alloy models were associated with less staphylococcal and Candida biofilm formation when compared with PEEK.

In vitro Inhibition of Biofilm Formation on Silicon Rubber Voice Prosthesis: Α Systematic Review and Meta-Analysis

Introduction: Biofilm formation on voice prostheses is the primary reason for their premature implant dysfunction. Multiple strategies have been proposed over the last decades to achieve inhibition of biofilm formation on these devices. The purpose of this study was to assess the results of the available in vitro biofilm inhibition modalities on silicone rubber voice prostheses. Methods: We conducted a systematic search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases up to February 29, 2020. A total of 33 in vitro laboratory studies investigating the efficacy of different coating methods against Candida, Staphylococcus, Streptococcus, Lactobacilli, and Rothia biofilm growth on silicone rubber medical devices were included. Subgroup analysis linked to the type of prevention modality was carried out, and quality assessment was performed with the use of the modified CONSORT tool. Results: Data from 33 studies were included in qualitative analysis, of which 12 qualified for quantitative analysis. For yeast biofilm formation assessment, there was a statistically significant difference in favor of the intervention group (standardized mean difference [SMD] = −1.20; 95% confidence interval [CI] [−1.73, −0.66]; p < 0.0001). Subgroup analysis showed that combined methods (active and passive surface modification) are the most effective for biofilm inhibition in yeast (SMD = −2.53; 95% CI [−4.02, −1.03]; p = 0.00001). No statistically significant differences between intervention and control groups were shown for bacterial biofilm inhibition (SMD = −0.09; 95% CI [−0.68, 0.46]; p = 0.65), and the results from the subgroup analysis found no notable differences between the surface modification methods. After analyzing data on polymicrobial biofilms, a statistically significant difference in favor of prevention methods in comparison with the control group was detected (SMD = −2.59; 95% CI [−7.48, 2.31]; p = 0.30). Conclusions: The meta-analysis on biofilm inhibition demonstrated significant differences in favor of yeast biofilm inhibition compared to bacteria. A stronger inhibition with the application of passive or combined active and passive surface modification techniques was reported.

Nanocarriers of Miconazole or Fluconazole: Effects on Three-Species Candida Biofilms and Cytotoxic Effects In Vitro.

The contribution of different Candida species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on Candida biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms (Candida albicans/Candida glabrata/Candida tropicalis) were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan—“IONPs-CS”) of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey’s or Fisher LSD’s tests (p < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight Candida biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections.

Electroanalysis of Candida albicans biofilms: A suitable real-time tool for antifungal testing

Candida albicans is a fungal pathogen that accounts for more than a million death annually. Analysis of Candida biofilms and rapid assessment of antifungal therapy is a critical challenge in clinical practice. Current biochemical methods are time-consuming and expensive or require expert interpretation of the results. Hence, there is the need for a rapid anti-fungal and anti-biofilm test. While electroanalysis has been previously adopted to determine antibiotic susceptibility in bacterial biofilms, there are no studies on yeast and fungi. In this work, electroanalysis of C. albicans biofilm and evaluation of anti-biofilm activity of several antifungal compounds using screen-printed carbon electrodes (SPEs) are reported. Results are compared with standard biochemical and microscopic methods. The current output decreases by 47.5%, 73.4%, and 88.5% in biofilms treated with the antifungals fluconazole (Flz), amphotericin B (AmB), and complex Ag3, respectively, indicating the suitability of electrochemical testing for evaluation of antifungal drugs. Chronoamperometry allows measuring antifungal activity on Candida biofilm as early as 10 h after inoculation, which show promises for the development of bioelectrochemical sensors in clinical settings.

Whole slide imaging is a high-throughput method to assess Candida biofilm formation

New strategies that enable fast and accurate visualization of Candida biofilms are necessary to better study their structure and response to antifungals agents. Here, we applied whole slide imaging (WSI) to study biofilm formation of Candida species. Three relevant biofilm-forming Candida species (C. albicans ATCC 10231, C. glabrata ATCC 2001, and C. tropicalis ATCC 750) were cultivated on glass coverslips both in presence and absence of widely used antifungals. Accumulated biofilms were stained with fluorescent markers and scanned in both bright-field and fluorescence modes using a WSI digital scanner. WSI enabled clear assessment of both size and structural features of Candida biofilms. Quantitative analyses readily detected reductions in biofilm-covered surface area upon antifungal exposure. Furthermore, we show that the overall biofilm growth can be adequately assessed across both bright-field and fluorescence modes. At the single-cell level, WSI proved adequate, as morphometric parameters evaluated with WSI did not differ significantly from those obtained with scanning electron microscopy, considered as golden standard at single-cell resolution. Thus, WSI allows for reliable visualization of Candida biofilms enabling both large-scale growth assessment and morphometric characterization of single-cell features, making it an important addition to the available microscopic toolset to image and analyse fungal biofilm growth.

In vitro activity of anidulafungin, caspofungin, fluconazole and amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies

ObjectiveThe aim of the present study was to evaluate the in vitro susceptibility of anidulafungin, caspofungin, fluconazole and conventional amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies. Materials and methodsAntifungal susceptibility for planktonic forms and biofilms of Candida was determined by broth microdilution method as described by Clinical and Laboratory Standards Institute M27 methodology and metabolic XTT-based [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay, respectively. ResultsA total of 75 Candida isolates were evaluated between 2006–2018 yy at the National Research Center for Hematology, Russia, Moscow. Biofilm production was detected in 34 (45.3%) Candida species. Antifungal susceptibility was tested for 27 common species of Candida forming biofilms (8 C.krusei, 7 C.tropicalis, 7 C.albicans, 5 C.parapsilosis).MICs below the susceptibility breakpoints were found for 100% of planktonic forms of Candida species for anidulafungin, 85.2% for caspofungin, and 66.7% for fluconazole. Amphotericin B MIC90 for Candida species were less than or equal to 1 μg/ml. Candida biofilms were susceptible in vitro for both tested echinocandins, but MIC80 of anidulafungin were lower compared to caspofungin. The highest MIC80 against Candida biofilms was found for fluconazole (>1,024 μg/ml for all tested isolates) and for conventional amphotericin B (range 4–16 μg/ml). ConclusionThe majority of Candida isolates grown as planktonic forms were susceptible to anidulafungin, caspofungin, conventional amphotericin B and fluconazole. Anidulafungin displayed higher activity against Candida biofilms than caspofungin. All Candida biofilms were resistant to fluconazole and conventional amphotericin B.

Efficacy of true cinnamon (Cinnamomum verum) leaf essential oil as a therapeutic alternative for Candida biofilm infections.

Objective(s):The essential oil (EO) extracted from Cinnamomum verum leaves has been used as an antimicrobial agent for centuries. But its antifungal and antibiofilm efficacy is still not clearly studied. The objective of this research was to evaluate the in vitro antifungal and antibiofilm efficacy of C. verum leaf EO against C. albicans, C. tropicalis, and C. dubliniensis and the toxicity of EO using an in vitro model.Materials and Methods:The effect of EO vapor was evaluated using a microatmosphere technique. CLSI microdilution assay was employed in determining the Minimum Inhibitory (MIC) and Fungicidal Concentrations (MFC). Killing time was determined using a standard protocol. The effect of EO on established biofilms was quantified and visualized using XTT and Scanning Electron Microscopy (SEM), respectively. Post-exposure intracellular changes were visualized using Transmission Electron Microscopy (TEM). The toxicological assessment was carried out with the Human Keratinocyte cell line. The chemical composition of EO was evaluated using Gas Chromatography-Mass Spectrometry (GC-MS).Results:All test strains were susceptible to cinnamon oil vapor. EO exhibited MIC value 1.0 mg/ml and MFC value 2.0 mg/ml against test strains. The killing time of cinnamon oil was 6 hr. Minimum Biofilm Inhibitory Concentration (MBIC50) for established biofilms was <0.2 mg/ml for all test strains. SEM images exhibited cell wall damages, cellular shrinkages, and decreased hyphal formation of Candida. TEM indicated intracellular vacuolation, granulation, and cell wall damages. Cinnamon leaf oil caused no inhibition of HaCaT cells at any concentration tested. Eugenol was the abundant compound in cinnamon oil.Conclusion:C. verum EO is a potential alternative anti-Candida agent with minimal toxicity on the human host.

Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods.

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.

Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045–0.07 mg/L), Satureja macrosiphon (0.06–8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs.

Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections.

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms.

Antimicrobial Peptides Pom-1 and Pom-2 from Pomacea poeyana Are Active against Candidaauris, C. parapsilosis and C. albicans Biofilms.

Recently two peptides isolated from the Cuban freshwater snail Pomacea poeyana (Pilsbry, 1927) were described to have antimicrobial activity against bacterial pathogens. Here we show considerable activities of Pom-1 and Pom-2 to reduce the viability of C. albicans, C. parapsilosis and the less common species C. auris measured as the decrease of metabolic activity in the resazurin reduction assay for planktonic cells. Although these activities were low, Pom-1 and Pom-2 turned out to be highly potent inhibitors of biofilm formation for the three Candida species tested. Whereas Pom-1 was slightly more active against C. albicans and C. parapsilosis as representatives of the more common Candida species Pom-2 showed no preference and was fully active also against biofilms of the more uncommon species C. auris. Pom-1 and Pom-2 may represent promising lead structures for the development of a classical peptide optimization strategy with the realistic aim to further increase antibiofilm properties and other pharmacologic parameters and to generate finally the first antifungal drug with a pronounced dedication against Candida biofilms.

Aspirin as an Antifungal-Lock Agent in Inhibition of Candidal Biofilm Formation in Surgical Catheters.

BackgroundThe antibiotic lock technique (ALT) has been recommended for the prevention and treatment of catheter-related candidaemia. Biofilms of Candida species are resistant to some of the antifungal agents currently used. Aspirin has been shown to have anti-fungal effect but its effect on candidal biofilm is poorly understood.PurposeThe aim of the current study was to evaluate the anti-biofilm effect of aspirin on Candida biofilms including C. albicans, C. glabrata, C. krusei and C. tropicalis formed on surgical catheters and the concentration and time required to eradicate the biofilms.MethodsBiofilms of Candida species were grown on silicone catheters and incubated in aspirin at different concentrations for 2, 4 and 24 hours. The biofilms remaining were then determined quantitatively by colony-forming unit (CFU) counts and XTT assays.ResultsThe results demonstrated that among the tested Candida species, C. albicans was the most sensitive species towards aspirin. Aspirin at a concentration of 40 mg/mL in 4 hours was effective in eradicating the biofilm. For all the other tested species, they were eradicated by aspirin at a concentration of 40 mg/mL in 24 hours.ConclusionOur results showed that aspirin may be used as an anti-fungal agent in lock therapy in the treatment of catheter-related candidaemia.