Effective Antifungal Activity Research Articles

Fabrication of water-resistance and durable antimicrobial adhesion polyurethane coating containing weakly amphiphilic poly(isobornyl acrylate) Side chains

Polyurethane (PU) coatings are the most preferred systems in widespread applications on account of their great variability and fine-tuning of material properties. In this work, we have developed an eco-friendly antimicrobial polyurethane with natural-sourced isobornyl antifoulant side chains. A key development is the preparation of weakly amphiphilic poly(isobornyl acrylate) (PIBA) with terminal dihydroxy by thiol-ene ‘click’ reaction under UV catalysis. Then, the macro-polyol rich in isobornyl group is incorporated as a chain extender to achieve the functionalized polyurethane resin (PIBA-PU). Our study shows that the introduction of PIBA pendant long chains slightly affects the thermal behaviors of the soft and hard segments of PIBA-PU, and significantly improves the water-resistance of polyurethane coating as expected. The antibacterial and antifungal adhesion performances of the coatings are both substantially enhanced at higher content of PIBA. Leather-finishing application further indicates that PIBA-PU coated leather surfaces exhibit effective and long-lasting antifungal activity. The results suggest that functionalizing polyurethane with weakly amphiphilic acrylate long chains offers novel options for green coating design, whereby surface hydrophobicity and antimicrobial performances are both satisfactory and suitable for surface finishing.

Biologically-Active Heterocyclic Molecules with Aggregation-Induced Blue-Shifted Emission and Efficient Luminescence both in Solution and Solid States

Biocompatible materials with aggregation-induced emission (AIE) have potential biological applications in bio-imaging and bioprobes. Although many heterocyclic compounds have bio-applications, strong π-π stacking usually causes aggregation-caused quenching (ACQ) of their luminescence. The design of AIE-active heterocyclic systems is thus highly needed. In this work, new chalcones and their thienopyrimidine derivatives have been synthesized and their molecular structures were affirmed by elemental and spectral analyses. The compounds displayed high thermal stability, and the luminescence of selected chalcones was studied in the solution and solid states at different temperatures. Moreover, density functional theory (DFT) calculations were done to study the molecular geometry of the ground and first excited states and the intermolecular interactions of these compounds. The studied dyes exhibited AIE behavior with two unusual phenomena, where one derivative gave blue-shifted emission after aggregation, and another derivative emitted efficiently both in the solid and solution states to fill the gap between AIE and ACQ materials. The DFT calculations revealed that changing the electronic structure of a terminal group can drastically alter the aggregation mode of the interacting molecules and hence change the optical properties of AIE luminogens. The new compounds may have potential bio-applications as some of them showed effective antibacterial and antifungal activities.

Staphylococcus saprophyticus L-38 produces volatile 3,3-dimethyl-1,2-epoxybutane with strong inhibitory activity againstAspergillus flavus germination and aflatoxin production

Controlling proliferation and aflatoxin production byAspergillus flavus is a pressing challenge for global food safety and security. Marine bacteriumStaphylococcus saprophyticus strain L-38 showed excellent antifungal activity towardA. flavus in vitro andin vivo. In sealed, non-contact confrontation assays, L-38 completely inhibited conidial germination and mycelial growth ofA. flavus through the production of volatile organic compounds (VOCs). Gas chromatography-mass spectrometry identified 3,3-dimethyl-1,2-epoxybutane (3-DE) as the most abundant VOC (32.61% of total peak area, 78% matching). Exposure ofA. flavus cultures to synthetic 3-DE similarly demonstrated strong inhibition of growth. Moreover, culture of L-38 in a sealed chamber with maize or peanuts artificially inoculated withA. flavus, at high water activity, resulted in significant inhibition ofA. flavus germination and aflatoxin biosynthesis. Scanning electron microscopy of these samples revealed severe damage to conidial cells and hyphae compared to samples not exposed to L-38. L-38 also showed broad and effective antifungal activity toward eight other phytopathogenic fungi includingAspergillus niger, Fusarium verticillioides, Fusarium graminearum, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria alternata, Monilinia fructicola, andBotrytis cinerea. This work introducesS. saprophyticus L-38 as a potential biocontrol agent and demonstrates the efficacy of the volatile 3-DE in the control ofA. flavus and other destructive plant pathogens for post-harvest food safety.

A New Epi-neoverrucosane-type Diterpenoid from the Liverwort Pleurozia subinflata in Borneo

New bioactive 13-epi-neoverrucosane diterpenoid, 5β-acetoxy-13-epi-neoverrucosanic acid (1) along with three known secondary metabolites, 13-epi-neoverrucosan-5β-ol (2), chelodane (3) and (E)-β-farnesene (4) were isolated from the MeOH extract of east Malaysia’s liverwort Pleurozia subinflata. The chemical structure of new compound was elucidated by the analyses of its spectroscopic data (FTIR, NMR and HR-ESI-MS). These epi-neoverrucosane-type compounds seem to be notable chemosystematic markers for P. subinflata in Borneo. Compound 3 was widespread in marine sponges however this is the first record for 3 to be found in liverwort. These metabolites were tested for their antifungal potentials against selected fungi from the marine environment. Compound 1 exhibited effective antifungal activity against Lagenidium thermophilum.Graphic

Date palm and saw palmetto seeds functional properties: antioxidant, anti-inflammatory and antimicrobial activities

The agricultural by-products are a significant source of health benefiting bioactive compounds. In this trend, the phenolic and flavonoid contents and functional properties of date palm seeds (DPS) and saw palmetto seeds (SPS) extracts were evaluated in this study. Considerable phenolic and flavonoid contents of 11.8, 7.75 mg GAE/g seed and 3.13, 1.1 mg CE/g seed were detected in DPS ethanol and SPS acetone extracts, respectively. The protocatechuic acid was the major compound in SPS and DPS extracts and represented 1.41 and 1.1 mg/g seed, respectively as well as similar phenolic compounds were detected using HPLC analysis. The DPS and SPS phenolic compounds possessed a strong antioxidant activity with IC50 values of 10.0, 2.2 and 2.0, 0.6 µg GAE/mL, using the DPPH and ABTS assays, respectively. The phenolic compounds of DPS and SPS extracts showed a potent and broad anti-bacterial activity against clinical multiple drug resistance bacterial strains with lower MIC values besides an effective anti-fungal activity against a number of human pathogenic fungal strains. Interestingly, in a model of LPS-induced inflammation in RAW 264.7 cells, DPS and SPS showed efficient anti-inflammatory effects to inhibit the iNOS protein expression and activity (NO release).

Synthesis, Characterization and Antimicrobial Studies of SnO2 Nanoparticles

This study was involved to synthesize and investigate the antimicrobial properties of highly pure nanocrystalline SnO2 by simple chemical method. In the nanorods, SnO2 nanoparticles, with a size of about 74 nm, the SnO2 nanoparticles were maximum antibacterial activity against both bacterial and fungal with the zone of inhibition for Klebsiella pneumoniae, Staphylococcus aures, Salmonella typhi and Ascerpergillus Flavus, Ascerpergillus Niger from 25μg/ml and 100 μg/ml respectively. SnO2 nanoparticles showed good activity against both Gram-negative and Gram-positive bacteria confirming these as future broad spectrum antibacterial a cost effective way and to study its antimicrobial properties. We observed an effective antibacterial and antifungal activity of the SnO2 nanoparticle against bacteria and fungi. The results showed that SnO2 nanoparticles enhanced the good antibacterial activity.

A green deposition method of silver nanoparticles on textiles and their antifungal activity

This study aims to propose a new green method for the deposition of silver nanoparticles (AgNPs) on textiles without the use of chemical compounds as binders. The deposition of AgNPs on textiles was achieved by immersing textiles in silver nitrate solution before adding with a natural reducing agent obtained from the extraction of Mikania micrantha. Plasmonic properties of the synthesized AgNPs were characterized using Ultraviolet-visible (UV–vis) spectroscopy and surface morphology of textiles was identified using the field-emission scanning electron microscopy (FESEM). In addition, energy-dispersive X-ray spectroscopy was also employed for the characterization. Inhibition zone measurement was performed for evaluating the antifungal capability of textiles attached with AgNPs. This study showed that the attachment of AgNPs to several textile types (cotton, cotton-polyester, silk, and fiber) without the use of binders or other chemical compounds had been successfully achieved. Moreover, all textiles attached with AgNP exhibited effective antifungal activity.

The endophytic strain Bacillus velezensis OEE1: An efficient biocontrol agent against Verticillium wilt of olive and a potential plant growth promoting bacteria

The use of antagonists in the biocontrol of soilborne pathogens is a promising approach to manage many diseases. In this context, Bacillus velezensis strain OEE1, isolated from endogenous root tissue of olive trees, showed the most effective antifungal activity under in vitro conditions against V. dahliae with inhibition rate exceeding 92% using the dual culture method to investigate effects of diffusible compounds. This antagonism was also demonstrated with volatile and extracellular compounds where fungus growth was reduced by about 40% and 60% respectively. Gnotobiotic study of axenic in vitro olive plants, artificially inoculated with V. dahliae, using B. velezensis OEE1 cells led to a considerable reduction in Verticillium wilt severity and the disease index effectively decreased for preventive and curative treatments. Vegetative growth showed equally an interesting improvement. These potentialities are provided due to the production of numerous secondary metabolites detected by antibiotic biosynthesis genes amplification. The efficacy of B. velezensis OEE1 to suppress Verticillium wilt of olive tree was evaluated also under field conditions. This experiment revealed that B. velezensis OEE1 significantly decreased final mean disease severity index (FMS), percentage of dead plants (PDP) and area under disease progress curve (AUDPC) and reduced similarly microsclerotia density in the naturally infested soil.

Antifungal Activity of Plant's Essential Oils against Post Harvest Fungal Disease of Apple Fruit

Bioactive natural compounds are developed as alternatives to synthetic fungicides for the control of rot diseases of apple fruit. The antifungal activity of essential oils exudes from five plants, namely, Cinnamomum tamala, Lantana camara, Ageratina adenophora, Citrus limetta and Eucalyptus citriodora were evaluated in vitro against Colletotrichum gloeosporioides, Fusarium oxysporum and Alternaria alternata causing postharvest rot disease in apple fruits. The pathogens were isolated from infected apple fruits collected from local markets of Kathamandu, Nepal. The essential oils were extracted through hydro-distillation process using Clevenger apparatus. The pathogenicity test was confirmed by inoculating pathogen into healthy apple fruit. The assessment of fungi toxicity was carried out by poison food technique using five different concentrations: 2.5μl/ml, 5μl/ml, 10μl/ml, 20μl/ml and 40μl/ml and controls were set to determine percentage inhibition of mycelial growth to test fungi. Among tested five essential oils, Cinnamomum tamala showed most effective antifungal activity against all three pathogens, which inhibited mycelium growth by 100% at 40 μl/ml concentrations. However, Eucalyptus citriodora showed all three pathogens inhibited mycelium growth by 65.87%, 73.17% and 86.91%, respectively at 40 μl/ml concentration.

EVALUATION OF ANTIMICROBIAL ACTIVITY AND PHYTOCHEMICALS ANALYSIS OF WHOLE PLANT EXTRACT OF VINCA ROSEA

Objectives: The aim of this research work was to find out the antibacterial activity and phytochemical analysis of whole plant extracts (shoot, flower, and root) of Vinca rosea.
 Methods: In recent work, phytochemicals were extracted from various parts of the plants using various solvents ethyl acetate (ETOAC), ethanol (ETOH), and dimethyl sulfoxide (DMSO). These phytochemicals contain alkaloids, terpenoids, tannins, flavonoids, aminoacids, saponins, aromatic acids, phenolic compounds, triterpenoids, xantho proteins, PHILOBATININS, carbohydrate, reducing sugar, and proteins; and they were separated by the standard methods. Moreover, antimicrobial activities of methanolic separation were determined by a different species of bacteria and fungi. Agar well-diffusion method was used for the antimicrobial activity, and also analyzed the zone of inhibition.
 Results: The evaluation of phytochemical screening of extracts indicated the existence of alkaloids, terpenoids, tannins, flavonoids, aminoacids, saponins, aromatic acids, phenolic compounds, triterpenoids, xantho proteins, philobatinins, carbohydrate, reducing sugar, and proteins. All the tested bacteria and fungi were controlled efficiently, and the activities of the shoot extracts were better compared to flower and root extracts. ETOH extract of the shoot exhibited highest antifungal activity against Candida albicans, (17.34 mm), followed by Candida krusei (16.12 mm), Aspergillus niger (15.76), Mucor sp. (14.67 mm), and Rhizopus oryzae (13.46 mm), ETOH extract of the shoot exhibited highest antibacterial activity), when compared to flower and root extracts against Staphylococcus aureus (12.77 mm), followed by Pseudomonas aeruginosa (11.67 mm), Salmonella abony (10.23 mm), Escherichia coli (9.65 mm), Micrococcus luteus (8.95 mm. V. rosea shoot extracts highlighted effective antifungal activities compared with flower and root extracts against all the tested bacteria.
 Conclusion: Current studies have shown that the V. rosea plant contains significant antimicrobial activities in the ETOH extracts. The strong antifungal and antibacterial activities of V. rosea are owing to the presence of saponin, tannins, and flavonoids present in.

S-ethyl ethanethiosulfinate, a derivative of allicin, induces metacaspase-dependent apoptosis through ROS generation in Penicillium chrysogenum.

Allicin can be used as fumigant to protect food and cultural relics from fungal contamination because of its strong antifungal activity and the characteristics of high volatility and no residues. However, the obvious disadvantages such as high minimal inhibitory concentration and instability prevent it from wide application. In this study, a stable derivative of allicin, S-ethyl ethanethiosulfinate (ALE), was synthesized. We further explored its antifungal activity and apoptosis-inducing effect, as well as the underlying mechanism. ALE had an excellent capability of inhibiting spore germination and mycelial growth of Penicillium chrysogenum observed by inverted microscope and scanning electron microscopy. XTT colorimetric assay indicated ALE could reduce the cell viability obviously and IC50 was 0.92 μg/ml, only 1/42 of allicin (38.68 μg/ml). DHR 123 ROS Assay Kit, flow cytometry assay and confocal immunofluorescence revealed intercellular ROS generation and metacaspase-dependent apoptosis triggered by ALE, while antioxidant tocopherol could reverse ALE-induced cytotoxicity effect and metacaspase activation. These results indicate that ALE induces metacaspase-dependent apoptosis through ROS generation, thus possesses an effective antifungal activity. This new derivative of allicin might be developed as a high efficient alternative to the conventional fungicides for food storage and cultural relic protection.

Efficacy of essential oils of various aromatic plants in the biocontrol of Fusarium wilt and inducing systemic resistance in chickpea seedlings

This study evaluated the antifungal activity of essential oils (EOs) against Fusarium oxysporum f.sp. ciceris Padwick (FOC) and their effects in inducing systemic resistance in chickpeas. The EOs chemical composition was analysed by GC-MS. Carvacrol, geraniol and 1,8-cineole were the major constituents in thyme, lemongrass and laurel EOs. The latter showed effective antifungal activity against FOC. In vivo tests revealed that thyme and lemongrass EOs were also very effective in reducing the severity in chickpeas and reached an inhibition rate of 99.3 and 88.9%, respectively. Chickpea resistance is mostly attributed to phenolic compounds accumulation. The highest content of polyphenols was obtained with thyme (22.7 to 57.5 mg/g). The studied EOs could be used as promising antifungal agents in preventing the occurrence of Fusarium wilt in chickpeas.

PHYTOCHEMICAL ANALYSIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY IN THE WHOLE PLANT EXTRACTS OF GLORIOSA SUPERBA

Objectives: The aim of this research work was to carry out the phytochemical screening and to evaluate the antibacterial and antifungal activity of the whole plant extract (shoot, flower, and tuber) of the flame lily (Gloriosa superba).
 Materials and Methods: In the current work, phytochemicals were extracted from different parts of the plant using different solvents dimethyl sulfoxide, ethyl acetate, and ethanol (ETOH). These phytochemicals contained alkaloids, flavonoids, terpenoids, tannins, saponins, aromatic acids, phenolic compounds, xanthoproteins, triterpenoids, amino acids, philobatinins, carbohydrate, reducing sugar, and proteins and they were separated using standard methods. Furthermore, antimicrobial activities of methanolic separation were determined using various species of bacteria and fungi. Agar well diffusion method was used for the antimicrobial activity and the zone of the inhibition was analyzed.
 Results: The evaluation of preliminary phytochemical screening of extracts indicated the presence of carbohydrates, reducing sugars, proteins, amino acids, steroids, flavonoids, terpenoids, saponins, alkaloids, tannins, and phlobatannins. Tuber extracts highlighted effective antibacterial and antifungal activities compared with shoot and flower extracts against all the tested bacteria and fungi. ETOH extract of the tuber observed highest antibacterial activity against Staphylococcus aureus (19 mm), followed by Escherichia coli (18 mm), Micrococcus luteus (17 mm), Pseudomonas aeruginosa (17 mm), and Salmonella abony (16 mm) when compared to shoot and flower extracts. G. superba tuber extracts highlighted effective antifungal activities compared with shoot and flower extracts against all the tested fungi. ETOH extract of the tuber observed highest antifungal activity against Rhizopus oryzae (20.17 mm), followed by Mucor Sp. (19.87 mm), Aspergillus niger (18.02), Candida krusei (17.98 mm), and Candida albicans (16.88 mm) as compared to shoot and flower extracts.
 Conclusion: Results of the current studies flame lily ETOH extracts showed that the plant has significant antimicrobial activities. The strong antibacterial and antifungal activities of flame lily are due to the presence of tannins and flavonoids present in.

Synthesis of a novel anti-freezing, non-drying antibacterial hydrogel dressing by one-pot method

As materials for the promotion of wound healing, hydrogel dressings must be usable for a long time or under extreme conditions. Traditional hydrogel dressings are often used for a short time mainly due to water loss at high temperature or water freezing at low temperature. This paper reports a facile approach to synthesize a novel antibacterial hydrogel wound dressing based on polyvinylpyrrolidone acrylamide 1-vinyl-3-butylimidazolium and polyethylene glycol dimethacrylate via one-pot method. This hydrogel has cationic groups in the polymer chains and exhibits effective antibacterial and antifungal activity. Furthermore, this hydrogel has anti-freezing, non-drying, and self-healing properties because of its unique molecular structure. Results of wound closure and histopathological examinations demonstrate that the fabricated hydrogel wound dressing effectively promotes the wound healing process in a full-thickness skin defect model. Therefore, this antibacterial hydrogel may be used as a wound healing dressing, even under extreme conditions.

PHYTOCHEMICAL SCREENING, ANTIMICROBIAL, AND ANTIOXIDANT ACTIVITIES OF ROOT AND LEAF EXTRACTS OF LEUCAS ASPERA

Objective: The present study was designed to evaluate the phytochemical screening, antimicrobial, and antioxidant activities from the roots and leaves of Leucas aspera.
 Methods: The phytochemical screening and Fourier transform infrared (FTIR) analysis of root and leaf extracts were studied using standard methods. The disk diffusion method was performed to analyze the antimicrobial activity of aqueous extract, methanol extract and hexane extract of root and leaf against to selected bacterial and fungal strains. Antibiotics, streptomycin and nystatin were used as standards for bacteria and fungi, respectively. The antioxidant activity of the extracts was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and scavenging of H2O2 free radicals.
 Results: Preliminary phytochemical screening of extracts exhibited the presence of carbohydrates, proteins, amino acids, steroids flavonoids, terpenoids, saponins, alkaloids, tannins, and phlobatannins. Leaf extracts exhibited effective antibacterial and antifungal activities compared with root extracts against all the tested bacteria and fungi. ME of the leaves exhibited highest antibacterial activity against Staphylococcus aureus (12.8±0.31 mm), followed by Bacillus subtilis (11.4±0.3 mm), Escherichia coli (9.8±0.21 mm), and Pseudomonas aeruginosa (7.3±0.29 mm). Leaf extracts of L. aspera showed effective scavenging activity compared with root extracts. ME of the leaves showed maximum scavenging activities of 38.39 and 36.85%, respectively, against DPPH and H2O2 free radicals with half maximal inhibitory concentration values of 136.17 and 142.42 μg/ml.
 Conclusion: Phytochemical analysis and FTIR spectrum revealed that different plant secondary metabolites particularly alkaloids, terpenoids, and flavonoids could be responsible for antimicrobial and antioxidant activities of L. aspera leaf extracts.

Chemical Composition and Antimicrobial Activity of Essential Oil and Various Extracts of Onosma sieheana Hayek Roots

:The present study reports the chemical composition and antimicrobial activity of Onosma sieheana roots. Essential oil (EO) and extracts were isolated from the roots of Onosma sieheana by hydrodistillation and Soxhlet extraction, respectively. Essential oil and methanol extract were further analyzed by using the Gas chromatography-Mass spectrometry (GC/MS) technique. The extraction yields were 6.50, 0.35, and 1.70 with methanol, petroleum ether, ethyl acetate, respectively, and 0.07% for essential oil. Exactly sixty-one compounds were identified in essential oil and twenty-three compounds were identified in methanol extract. The main component of the essential oil was p-cymene (27.32%), whereas the main component of the methanol extract was methyl palmitoleate (15.19%). Although, the essential oil extracted from the roots of Onosma sieheana by the hydrodistillation method, was characterized by a high level of sesquiterpenes, the one extracted from Onosma sieheana roots by the Soxhlet extraction method was characterized by a high level of monoterpenes. Subsequently, these extracts were investigated for their antibacterial activity against two Gram- positive and two Gram-negative strains as well as for their antifungal activity against two yeast strains. As a result of antimicrobial studies, it has been determined that essential oil of Onosma sieheana roots have more effective antifungal activity than antibacterial activity. The antimicrobial effects of the extracts were found to be similar.

In vitro Antifungal Activity of a New Bioproduct Obtained from Grape Seed Proanthocyanidins on Botrytis cinerea Mycelium and Spores

Botrytis cinerea is a necrotrophic fungus that affects over 200 plant species. In vineyards, this pathogen is responsible for one of the most important diseases, commonly known as botrytis bunch rot or grey mould. Keeping infection under control with synthetic fungicides leads to an increased biological resistance of pathogen populations. An alternative way to synthetic products is to obtain natural fungicides by using bioactive compounds of plants. This study focuses on the antifungal properties of a new bioproduct obtained from polymeric proanthocyanidins extracted from grape seeds of ‘Fetească neagră’ variety. The bioproduct in solid state presented a total content of polyphenols of 0.625 mg GAE mg-1, a polyphenolic index of 17.40 and an antioxidant activity of 91.27% scavenged DPPH. The bioproduct with polyphenolic structure showed a moderate effect on the radial growth of fungal mycelium, at EC50 values between 11.23 and 12.15 mg mL-1. Effective antifungal activity was showed in the inhibition of spore germination, where the EC50 values varied from 1.14 to 1.47 mg mL-1. These in vitro results sustain the possibility of including the bioproduct in the category of natural fungicides for biological control against Botrytis cinerea fungus.

Molybdenum disulfide nanosheets loaded with chitosan and silver nanoparticles effective antifungal activities: in vitro and in vivo

A method was developed for the liquid exfoliation of molybdenum disulfide (MoS2) from its bulk materials using ultrasound in aqueous phase with the assistance of chitosan (CS) and silver nanoparticles (Ag NPs) for effective loading of a variety of therapeutic molecules. The characterization results revealed that the as-made chemically-exfoliated MoS2 nanosheets had an average thickness of ∼10 nm. The new material, CS and Ag NPs-modified MoS2 (MoS2-CS-Ag), showed highly effective antifungal activities against Saccharomyces uvarum and Aspergillus niger. The Ag NPs-loaded MoS2 nanosheets achieved outstanding antifungal effect by inhibiting fungal growth both in vitro and in vivo. Notably, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis of spore morphological changes caused by MoS2-CS-Ag treatment reveal that it may directly cause the cell death. The result of the analysis of the application of MoS2-CS-Ag as an antifungal for fruits also demonstrated the MoS2-CS-Ag protective properties against fungi. The excellent film-forming ability of CS has been shown to contribute to the effectiveness of MoS2-CS-Ag in preserving the freshness of fruits, exhibited in four chemical quality sections: Vc, total carbohydrate, weight loss, and titratable acidity in fruit preservation application assay. The present study reports a new and exciting insight in a multi-functional drug carrier for protecting postharvest fruit.

Risk-Adapted Anti-Mould Prophylaxis Improves Supportive Care in Childhood Leukemia Patients

BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematologic disease has traditionally been based on the widespread use of fluconazole. With the awareness of increasing rates of invasive mould infections, new agents have been developed and offered to patients at highest risk.METHODS: We compared the tolerance and outcome of different antifungal prophylaxis in 198 childhood patients treated for acute myeloid and lymphoblastic leukemia in a pediatric cancer center. Until 2011 antifungal prophylaxis with fluconazole was offered to all patients, resulting in 15.2-19.4% of invasive mould infections. As the burden of fungal infections was restricted to high risk patients only (i.e. acute myeloid leukemia, leukemia relapse, high risk acute lymphoblastic leukemia and patients after stem cell transplant) and no infection with candida was registered, antifungal prophylaxis was replaced with liposomal amphotericin and offered to this particular patient group.RESULTS: Liposomal amphotericin was well tolerated; there was no occurrence of infusion-related reaction and/or glomerular-associated nephrotoxicity. The development of vincristine-induced neurotoxicity was significantly reduced, as stool frequency was increased up to 38% in patients treated with liposomal amphotericin (p = 0.024). Importantly, there was a marked shift in the percentage of patients with severe constipation (15.5% versus 4.2%, fluconazole versus liposomal amphotericin respectively, p = 0.010). Notably, with limitation of prophylactic treatment to high risk patients a major group of patients did not receive any antifungal prophylaxis (48.81%) and most importantly, the occurrence of invasive fungal infection was completely prevented (p = 0.021). In comparison, 10 patients in the fluconazole group developed proven invasive pulmonary infections. Of these, 6 patients developed disseminated disease, and 4 patients died. Aspergillus was isolated in 40% and rhizopus in 30% of biopsy specimens.CONCLUSION: Polyene prophylaxis offers effective antifungal activity with improved tolerability compared to older agents. The potential impact of this treatment should be included in current prophylaxis guidelines of antileukemic treatment. DisclosuresNo relevant conflicts of interest to declare.

Novel Approaches for Efficient Antifungal Drug Action.

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.