Treatment Of Fungal Infections Research Articles

In vitro assessment of the immobilized mannanase enzyme against infection-causing Candida.

Background: Developing an effective treatment for fungal infections is among contemporary medicine's challenges. In this study we aimed to eradicate mannan in pathogenic Candidae's cell walls using a nontoxic method, mannanase. Materials & Methods: We investigated the in vitro antifungal activities of mannanase immobilized on zinc oxide nanoparticles (ZnONps) and reduced graphene oxide nanoparticles (RGONps), as well as therapeutics against Candidae. Mannanase was purified from Bacillus invictae (activity: 5.15EU/ml;range: 60-80%) and then immobilized it to ZnO and RGO to enhance its effectiveness. Results: Mannanase immobilized on ZnONps had the highest activity, with a value of 4.97EU/ml, more effective than amphotericin-B. However, it could not reach the inhibition rates of other antifungals. Conclusion: Mannanase immobilized on ZnONps could be an effective fungicide for Candida biocontrol.

Photothermal/Photoacoustic Therapy Combined with Metal-Based Nanomaterials for the Treatment of Microbial Infections.

The increased spread and persistence of bacterial drug-resistant phenotypes remains a public health concern and has contributed significantly to the challenge of combating antibiotic resistance. Nanotechnology is considered an encouraging strategy in the fight against antibiotic-resistant bacterial infections; this new strategy should improve therapeutic efficacy and minimize side effects. Evidence has shown that various nanomaterials with antibacterial performance, such as metal-based nanoparticles (i.e., silver, gold, copper, and zinc oxide) have intrinsic antibacterial properties. These antibacterial agents, such as those made of metal oxides, carbon nanomaterials, and polymers, have been used not only to improve antibacterial efficacy but also to reduce bacterial drug resistance due to their interaction with bacteria and their photophysical properties. These nanostructures have been used as effective agents for photothermal therapy (PTT) and photodynamic therapy (PDT) to kill bacteria locally by heating or the controlled production of reactive oxygen species. Additionally, PTT or PDT therapies have also been combined with photoacoustic (PA) imaging to simultaneously improve treatment efficacy, safety, and accuracy. In this present review, we present, on the one hand, a summary of research highlighting the use of PTT-sensitive metallic nanomaterials for the treatment of bacterial and fungal infections, and, on the other hand, an overview of studies showing the PA-mediated theranostic functionality of metal-based nanomaterials.

A review on Luliconazole for the treatment of fungal infections: an evidence

A review on Luliconazole for the treatment of fungal infections: an evidence

Graphene Scaffolds: A Striking Approach to Combat Dermatophytosis.

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes.

Exponential Rise of Fungal Infection Reported in Rajkot Civil Hospital in Covid Pandemic Era: A Retrospective Study.

Mucormycosis is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes. Mucormycosis is an aggressive, life-threatening infection requiring prompt diagnosis and early treatment. Wide spread use of steroid and higher antibiotics may cause immune irregulation in post covid patients. A hallmark of mucormycosis infection is the presence of extensive angioinvasion with resultant vessel thrombosis and tissue necrosis. We reported exponential rising cases of fungal infection in covid pandemic era. Here we published epidemiological data of 773 fungal infected cases operated in ENT department of PDU Medical college, Rajkot in 2021. We have documented patients demographic data with comorbidity, paranasal sinuses with orbital, palatal and cerebral involvement, evaluation method, surgical and post surgical management protocol which we followed in our institute to treat all cases. We got promising result in terms of survival and less morbidity. Early presentation, less comorbidity, proper evaluation and immediate debridement with systemic antifungal coverage for adequate duration proved to be mainstay treatment of fungal infection in covid pandemic era.

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity.

Luliconazole (LZ) is a good candidate for the treatment of fungal infection topically but has limitations, i.e., poor solubility and poor permeability to skin. Due to these limitations, multiple administrations for a long time are required to treat the inflection. The aim of the present study was to develop the invasomes (IVS) gel of LZ to improve the topical antifungal activity. The IVS was prepared by the thin-film hydration method and optimized by Box-Bhekhen design software. The optimized LZIVS (LZIVSopt) has 139.1 ± 4.32 nm of vesicle size, 88.21 ± 0.82% of entrapment efficiency, 0.301 ± 0.012 of PDI, and 19.5 mV (negative) of zeta potential. Scanning microscopy showed a spherical shape of the vesicle. FTIR spectra showed there is no interaction between the drug and lipid. Thermogram showed that the LZ is encapsulated into the LZIVS matrix. LZIVSopt gel (LZIVSopt-G3) exhibited optimum viscosity (6493 ± 27 cps) and significant spreadability (7.2 g·cm/s). LZIVSopt-G3 showed 2.47-fold higher permeation than pure LZ-gel. LZIVSopt-G3 did not show any edema or swelling in the skin, revealing that the developed formulation is non-irritant. LZIVSopt-G3 exhibited significant inhibition of the fungus infection (C. albicans) in the infected rats. The finding concluded that IVS gel is a good carrier and an attractive approach for the enhancement of topical delivery of LZ to treat the fungal infection.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000ng/mL and 3000-4999ng/mL (80% vs. 58.8%; P=0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000ng/mL should be considered.

Efficacy and influencing factor analysis of Voriconazole in the treatment of invasive fungal infections

Current study aims to explore the correlation between the administered dose and efficacy of voriconazole in the treatment of invasive fungal infection (IFI). The correlation between different doses of Voriconazole and plasma concentrations as well as clinical efficacy was counted. Consequently, 40 strains of pathogenic micro-organisms were isoninelated and cultured from etiological samples. A total of 66 patients with steady-state trough serum concentrations ranging from 1.0 to 5.5 μg/mL were measured, with a compliance rate of 79.5%. Chi-square test showed that there was a significant correlation between Voriconazole steady-state serum trough concentration and treatment efficacy. In addition, the result of Pearson test showed that steady-state trough serum concentration of Voriconazole was significantly positively correlated with the administered dose (γ = 0.866, P < 0.001). On conclusion, Voriconazole is effective in treatment of IFI, and there is a significant dose-plasma concentration correlation with efficacy.

Efficacy of garlic and cinnamon as an alternative to chemotherapeutic agents in controlling Saprolegnia infection in Nile tilapia

The objective of this study was to minimize the utilization of chemotherapeutic agents in the treatment of fungal infections in fish, as these agents can adversely impact human and animal health as well as the environment. Nile Tilapia was utilized in this study to assess the efficacy of incorporating garlic and cinnamon into their diet, aiming to enhance their immune systems and provide protection against Saprolegnia, a fungal pathogen that causes substantial economic losses in the fish farming industry. The findings indicated that the inclusion of garlic and cinnamon to the fish's diet enhanced their immune response and various blood parameters. Specifically, group 4, treated with 1.5% garlic, demonstrated superior outcomes compared to group 5, which received 2% garlic treatment. Additionally, group 6, subjected to 8.5% cinnamon treatment, exhibited superior hematological parameters when compared to group 7, which received 10% cinnamon treatment. Moreover, group 6 displayed the highest phagocytic activity in comparison to the remaining groups. In conclusion, garlic and cinnamon can serve as valuable immunostimulants for managing fungal infections in fish. Their inclusion in the diet enhances the immune response, consequently bolstering the fish's resistance to fungal infections.

Formulation and Development of Hyaluronic Acid based Gel with Ketoconazole-Loaded Nanostructured Lipid Carriers in Fungal Infection.

Ketoconazole is an imidazole ring containing antifungal agent used in the treatment of systemic fungal infections. It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane. The purpose of this work is to construct skin targeting ketoconazole nanostructured lipid carriers (NLCs) loaded hyaluronic acid (HA) modified gel to minimize side effects and provide a controlled release. The NLCs were prepared using emulsion sonication method and their optimized batches were characterized for X-ray diffraction, scanning electron microscopy and fourier transform infrared spectroscopy study. These batches were then incorporated into HA containing gel for convenient application. The final formulation was compared with the marketed formulation for studying its antifungal activity and drug diffusion. Ketoconazole NLCs loaded hyaluronic acid formulation was successfully developed with desirable formulation parameters by using 23 Factorial design. In vitro release study of developed formulation showed prolonged drug release (up to 5 hrs) while ex vivo drug diffusion study on human cadaver skin showed better drug diffusion as compared with marketed formulation. Moreover, the release study and diffusion study results reflected the improvement of antifungal activity of the developed formulation against Candida albicans. The work suggests that ketoconazole NLCs loaded HA modified gel provides prolonged release. The formulation also has good drug diffusion and antifungal activity and thus can act as a promising carrier for topical delivery of ketoconazole.

In silico and in vitro analysis of the mechanisms of action of nitroxoline against some medically important opportunistic fungi.

The increasing resistance to antifungal agents associated with toxicity and interactions turns therapeutic management of fungal infections difficult. This scenario emphasizes the importance of drug repositioning, such as nitroxoline - a urinary antibacterial agent that has shown potential antifungal activity. The aims of this study were to discover the possible therapeutic targets of nitroxoline using an in silico approach, and to determine the in vitro antifungal activity of the drug against the fungal cell wall and cytoplasmic membrane. We explored the biological activity of nitroxoline using PASS, SwissTargetPrediction and Cortellis Drug Discovery Intelligence web tools. After confirmation, the molecule was designed and optimized in HyperChem software. GOLD 2020.1 software was used to predict the interactions between the drug and the target proteins. In vitro investigation evaluated the effect of nitroxoline on the fungal cell wall through sorbitol protection assay. Ergosterol binding assay was carried out to assess the effect of the drug on the cytoplasmic membrane. In silico investigation revealed biological activity with alkane 1-monooxygenase and methionine aminopeptidase enzymes, showing nine and five interactions in the molecular docking, respectively. In vitro results exhibited no effect on the fungal cell wall or cytoplasmic membrane. Finally, nitroxoline has potential as an antifungal agent due to the interaction with alkane 1-monooxygenase and methionine aminopeptidase enzymes, which are not the main human therapeutic targets. These results have potentially revealed a new biological target for the treatment of fungal infections. We also consider that further studies are required to confirm the biological activity of nitroxoline on fungal cells, mainly the confirmation of the alkB gene.

Biological Activity of Biosynthesized Silver Nanoaggregates Prepared from the Aqueous Extract of Cymbopogon citratus against Candida spp.

Cymbopogon citratus is commonly used in folk medicine for the treatment of nervous and gastrointestinal disturbances and other medical issues because of its potent antioxidant capacity. The current study evaluated the anti-candida effects of silver nanoparticles (AgNPs) synthesized from an aqueous extract of C. citratus against different Candida spp. The aqueous extract was prepared from the fresh leaves of C. citratus. The silver nanoparticles (AgNPs) were prepared and validated by UV spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), and zeta size analysis. C. albicans, C. krusei, C. parapsilosis, C. tropicalis, C. famata, C. rhodotorula, and C. glabrata were used in the antifungal assay. Microscopical imaging were used to investigate the different morphological changes induced by treatment. FTIR spectrum confirmed the existence of various functional groups of biomolecules capping the nanoparticles. The average particle size of synthesized AgNPs was 100.6 nm by zeta-sizer and 0.012 to 0.059 mm by TEM. In the antifungal assay, AgNPs aggregates induced significant inhibition of the growth of all species (p < 0.05) compared to the control and the biofilm maturation in C. famata and C. albicans. These considerable antifungal activities might lead to the development of appropriate alternative remedy for the treatment of fungal infections.

Recent progression in nanocarrier based techniques to address fungal infections and patent status in drug development process.

Fungal infections are becoming one of the most common diseases in recent years, especially when it comes about dealing skin infections. Different drugs are available commercially with antifungal activity for topical application and are effective for treatment of mild to moderate fungal infections. However they lack dermal bioavailability due to their poor penetrability, and less retention at the site thereby resulting in poor efficacy. The remaining systemic treatment options available so far may cause adverse drug effects and many other complications. In recent years nano carrier based formulations promised to overcome the limitations of the conventional topical dosage forms. Lipid based nano carriers and their importance for potential use in delivery of antifungal agents for the treatment of superficial fungal infections have been well discussed in this review article. It comprises of different nano lipid systems involved in treatment of topical fungal infections, effect of different polymers on their size, stability, and their mechanistic action behind skin penetration and dermal retention of drug into deeper epidermal layers is also highlighted to depict recent efforts of researchers in this context. Further, the addressing of the disease by novel drug delivery systems for the efficacious treatment, status of clinical trials, novel commercial formulations available for use in dermal drug delivery and patents claimed/granted in the respective field have been discussed in detail.

Concentration, Life Stage, Feeding, Density, Flow, and Strain Effects on Formalin Sensitivity in Rainbow Trout (Oncorhynchus mykiss).

Formalin is one of the most widely used and effective chemotherapeutic compounds for treatment of fungal infections and external parasites of fish eggs and fish. However, exposure to formalin can cause mortality in eggs and fingerlings, dependent upon the concentration used and the rearing conditions in which fish are treated. Additionally, strains within a species can exhibit differential susceptibility to formalin. Four experiments were conducted to evaluate the differential sensitivity to formalin of four rainbow trout (Oncorhynchus mykiss) strains in both the egg and fingerling life stages. Eggs were exposed to concentrations of 1667, 2000, and 5000 ppm formalin, and sensitivity differed among the strains when formalin concentration exceeded 2000 ppm. Exposure to higher formalin concentrations (i.e., 5000 ppm) as eggs did not increase mortality when fish were re-exposed to concentrations of 0, 167, 250, or 500 ppm formalin at 77 mm total length (TL). Fish size affected formalin sensitivity, with larger fish (128 mm TL) exhibiting higher rates of mortality than fish ≤ 77 mm TL when exposed to 250 ppm formalin. The effects of crowding, feeding, flow, and density on the formalin sensitivity of 77 mm TL fish were also investigated. Mortality increased in fish crowded away from the inflow to prevent contact with formalin as it entered the tank, potentially the result of an increase in density index within the crowded tanks. Feeding fish on the day they were treated caused mortality to increase by 5.4 to 8.8% in fish exposed to 167 and 250 ppm formalin, respectively, and mortality differed by strain. Reducing flows by half resulted in doubled to quadrupled mortality, and increased densities resulted in increased mortality in some strains but not others. Hatchery managers should consider what effect rearing conditions and formalin concentrations might have on the strain of fish being treated, prior to large-scale treatment.

N-(((1S,5R)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)-3-dodecan/tetradecanamido-N,N-dimethylpropan-1-aminium Bromide

The syntheses of the title compounds were performed using lauric and myristic acids. The compounds obtained were characterized using 1H-, 13C-NMR and 2D 1H-1H COSY, 1H-13C HSQC NMR, IR, and high-resolution mass spectrometry. Both compounds exhibited bactericidal activity on S. aureus comparable to that of a reference drug (miramistin). Compound 10, with lauric acid fragment, had a 16-fold higher activity on P. aeruginosa compared to compound 11, which in turn contains myristic acid fragment (with minimum inhibitory concentrations of 32 and 512 μg/mL, respectively). Compound 11 exhibited a pronounced activity against all types of fungi (higher than the activity of miramistin), while the activity of compound 10 was considerably lower. Thus, compound 11 can serve as a promising antimicrobial agent for the treatment of various fungal and staphylococcal infections, while compound 10 is of interest to treat P. aeruginosa-associated infections.

Vesicular drug delivery systems for the fungal infections’ treatment through topical application-a systemic review

In this systemic review, we tried to explore and summarize the Vesicular Drug Delivery Systems (VDDSs) which can exclusively used for topical applications in the treatment of fungal infections. The specific algorithm is developed for this systemic review, exclusion criteria for the review were set and results were excluded which were meets the exclusion criteria. To build a review, Google Scholar® and PubMed® are two databases that are targeted so that we can collect the number of freely available full-text articles and can minimize the risk of bias (unavailability of full-text articles, for this study). By adopting the algorithm, searched articles were studied thoroughly and we found that thirteen types of VDDS were used by the researchers to treat skin infections caused by fungi in the last five years. From this current systemic review, we found a numbers of VDDSs are available for skin fungal infection, but all are not suitable for topical applications because of some drawbacks associated with some VDDS such as instability (Emulsomes), high cost of manufacturing (Sphingosomes), low transfer efficiency (Aquasomes), etc. As per the data analysed, we can say that; Liposomes, Ethosomes, Niosomes, Bilosomes, Cubosomes, and Ufasomes are the choices of researchers as VDDS in the therapy of different fungal diseases. Upcoming researchers can focus on these VDDSs in the treatment of infections spread on the skin by the fungi.

Can BioSAXS detect ultrastructural changes of antifungal compounds in Candida albicans?-an exploratory study.

The opportunistic yeast Candida albicans is the most common cause of candidiasis. With only four classes of antifungal drugs on the market, resistance is becoming a problem in the treatment of fungal infections, especially in immunocompromised patients. The development of novel antifungal drugs with different modes of action is urgent. In 2016, we developed a groundbreaking new medium-throughput method to distinguish the effects of antibacterial agents. Using small-angle X-ray scattering for biological samples (BioSAXS), it is now possible to screen hundreds of new antibacterial compounds and select those with the highest probability for a novel mode of action. However, yeast (eukaryotic) cells are highly structured compared to bacteria. The fundamental question to answer was if the ultrastructural changes induced by the action of an antifungal drug can be detected even when most structures in the cell stay unchanged. In this exploratory work, BioSAXS was used to measure the ultrastructural changes of C. albicans that were directly or indirectly induced by antifungal compounds. For this, the well-characterized antifungal drug Flucytosine was used. BioSAXS measurements were performed on the synchrotron P12 BioSAXS beamline, EMBL (DESY, Hamburg) on treated and untreated yeast C. albicans. BioSAXS curves were analysed using principal component analysis (PCA). The PCA showed that Flucytosine-treated and untreated yeast were separated. Based on that success further measurements were performed on five antifungal peptides {1. Cecropin A-melittin hybrid [CA (1-7) M (2-9)], KWKLFKKIGAVLKVL; 2. Lasioglossin LL-III, VNWKKILGKIIKVVK; 3. Mastoparan M, INLKAIAALAKKLL; 4. Bmkn2, FIGAIARLLSKIFGKR; and 5. optP7, KRRVRWIIW}. The ultrastructural changes of C. albicans indicate that the peptides may have different modes of action compared to Flucytosine as well as to each other, except for the Cecropin A-melittin hybrid [CA (1-7) M (2-9)] and optP7, showing very similar effects on C. albicans. This very first study demonstrates that BioSAXS shows promise to be used for antifungal drug development. However, this first study has limitations and further experiments are necessary to establish this application.

The emerging role of extracellular vesicles in fungi: a double-edged sword.

Fungi are eukaryotic microorganisms found in nature, which can invade the human body and cause tissue damage, inflammatory reactions, organ dysfunctions, and diseases. These diseases can severely damage the patient's body systems and functions, leading to a range of clinical symptoms that can be life-threatening. As the incidence of invasive fungal infections has progressively increased in the recent years, a wealth of evidence has confirmed the "double-edged sword" role of fungal extracellular vesicles (EVs) in intercellular communication and pathogen-host interactions. Fungal EVs act as mediators of cellular communication, affecting fungal-host cell interactions, delivering virulence factors, and promoting infection. Fungal EVs can also have an induced protective effect, affecting fungal growth and stimulating adaptive immune responses. By integrating recent studies, we discuss the role of EVs in fungi, providing strong theoretical support for the early prevention and treatment of invasive fungal infections. Finally, we highlight the feasibility of using fungal EVs as drug carriers and in vaccine development.

Reduced Survival and Resistance of Rhodotorula mucilaginosa Following Inhibition of Pigment Production by Naftifine.

Pigments produced by micro-organisms could contribute to their pathogenesis and resistance. The investigation into the red pigment of R. mucilaginosa and its ability to survive and resist has not yet been explored. This study aimed to investigate the survival and resistance of the R. mucilaginosa CQMU1 strain following inhibition of pigment production by naftifine and its underlying mechanism. The red-pigmented Rhodotorula mucilaginosa CQMU1 yeast was isolated from an infected toenail of a patient with onychomycosis. Cultivation of R. mucilaginosa in liquid and solid medium showed the effect of naftifine after treatment. Then, analysis of phagocytosis and tolerance to heat or chemicals of R. mucilaginosa was used to evaluate the survival and resistance of yeast to different treatments. Naftifine reversibly inhibited the pigmentation of R. mucilaginosa CQMU1 in solid and liquid media. Depigmented R. mucilaginosa CQMU1 showed increased susceptibility toward murine macrophage cells RAW264.7 and reduced resistance toward different types of chemicals, such as 1.5-M NaCl and 0.5% Congo red. Inhibition of pigment production by naftifine affected the survival and growth of R. mucilaginosa and its resistance to heat and certain chemicals. The results obtained could further elucidate the target of new mycosis treatment.

Antifungal Activities of Cassia angustifolia Leaf Ethanolic Extract against Various Candida Spp.

Indian senna (Cassia angustifolia) is a perennial shrub belonging to the family Fabaceae. Indian senna contains flavonoids, pinnitolos (polyols), acidic polysaccharides, and mineral substances. It also contains two types of glucosides known as sennosides A and B and other compounds, including myricyl alcohol, anthraquinone derivatives, galactose, arabinose, rhamnose, galacturonic acid, chrysophanic acid, salicylic acid, resin, and mannitol. The antifungal activity of the extract was assessed against fungal strains, including Candida albicans (ATCC10231), Candida parapsilosis, and Candida auris. The result showed that the leaf extract of Cassia angustofolia exhibits significant antifungal activity against all tested fungal strains. After the result, Indian Senna which could be used to develop new drugs for the treatment of resistant fungal infections. Further research and optimum preservation, and flavonoids extraction methods is needed, particularly in the developing world, where senna leaf and flower harvest processing methods are more traditional.