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BACKGROUND: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation. METHODS: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics. RESULTS: Of 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6-43.0) versus 38 (interquartile range, 15.9-211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117). CONCLUSIONS: Rezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population.

UNLABELLED: Identifying improved treatments for severe and refractory coccidioidomycosis (Valley fever) is needed. This endemic fungal disease is common in North and South America, and cases have increased substantially over the last 30 years. The current standard of care, oral daily fluconazole, often fails to completely eradicate Coccidioides infection; however, the high cost of identifying new compounds effective in treating Valley fever is a barrier to improving treatment. Therefore, repurposing existing pharmaceutical agents in combination with fluconazole therapy is an attractive option. We screened the Library of Pharmacologically Active Compounds (LOPAC) small molecule library for compounds that inhibited fungal growth in vitro and determined IC50 values for a subset of compounds. Based on these findings, we tested a small subset of these agents to validate the screen, as well as to test the performance of fluconazole in a combination therapy approach, as compared with fluconazole alone, in a murine model. We observed that combination therapy of tamoxifen:fluconazole and sertraline:fluconazole significantly reduced the burden of live fungus in the lung compared with fluconazole alone, and we observed reduced or nonexistent dissemination. These results suggest that tamoxifen and sertraline may be repurposed as adjunctive agents in the treatment of this important fungal disease. IMPORTANCE: Developing new drugs, especially for regional orphan diseases, such as Valley Fever, is a slow and costly endeavor. However, there is a wealth of FDA-approved drugs available for repurposing, offering a more economical and expedited approach to improve treatment. Those existing compounds with antifungal properties can become novel therapies with relative ease: a considerable advantage for patients in need of alternative treatment. Despite the scope of remaining tasks, our comprehensive screening of potential candidates has revealed promising combinations for further exploration. This effort outlines a practical pipeline for Valley fever drug screening and identifies viable drug combinations that could impact patients more rapidly than single drug development pathways.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [-13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [-16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [-0.2%, 40.2%]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

Candida parapsilosis is known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant C. parapsilosis (MDR Cp) isolates were identified in a large Turkish hospital from 2017-2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital. The increasing number of MDR and ECR isolates contradicts the general principle that the severe fitness cost associated with these phenotypes could prevent their dominance in clinical settings. Here, we employed a multidimensional approach to systematically assess the fitness costs of MDR and ECR C. parapsilosis isolates. Whole-genome sequencing revealed a novel MDR genotype infecting two patients in 2022. Despite severe in vitro defects, the levels and tolerances of the biofilms of our ECR and MDR isolates were generally comparable to those of susceptible wild-type isolates. Surprisingly, the MDR and ECR isolates showed major alterations in their cell wall components, and some of the MDR isolates consistently displayed increased tolerance to the fungicidal activities of primary human neutrophils and were more immunoevasive during exposure to primary human macrophages. Our systemic infection mouse model showed that MDR and ECR C. parapsilosis isolates had comparable fungal burden in most organs relative to susceptible isolates. Overall, we observed a notable increase in the genotypic diversity and frequency of MDR isolates and identified MDR and ECR isolates potentially capable of causing persistent outbreaks in the future.

UNLABELLED: Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer β-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae, Sclerotinia sclerotiorum and Monilinia fructicola. Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens.

PurposeTo assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM).MethodsIn this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality.ResultsAmong eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality.ConclusionsPatients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.

There is an ongoing need for antifungal agents to treat humans. Identification of new antifungal agents can be based on screening compounds using whole cell assays. Screening compounds that target a particular molecule is possible in budding yeast wherein sophisticated strain engineering allows for controlled expression of endogenous or heterologous genes. We have considered the yeast Mps1 protein kinase as a reasonable target for antifungal agents because mutant or druggable forms of the protein, upon inactivation, cause rapid loss of cell viability. Furthermore, extensive analysis of the Mps1 in budding yeast has offered potential tactics for identifying inhibitors of its enzymatic activity. One such tactic is based on the finding that overexpression of Mps1 leads to cell cycle arrest via activation of the spindle assembly checkpoint. We have endeavored to adapt this assay to be based on the overexpression of Mps1 orthologs from pathogenic yeast in hopes of having a whole-cell assay system to test the activity of these orthologs. Mps1 orthologous genes from seven pathogenic yeast or other pathogenic fungal species were isolated and expressed in budding yeast. Two orthologs clearly produced phenotypes similar to those produced by the overexpression of budding yeast Mps1, indicating that this system for heterologous Mps1 expression has potential as a platform for identifying prospective antifungal agents.

Pathogenic fungi employ numerous strategies to colonize plants, infect them, reduce crop yield and quality, and cause significant losses in agricultural production. The increasing use of chemical pesticides has led to various ecological and environmental issues, including the emergence of resistant weeds, soil compaction, and water pollution, all negatively impacting agricultural sustainability. Additionally, the extensive development of synthetic fungicides has adverse effects on animal and human health, prompting the exploration of alternative approaches and green strategies for phytopathogen control. Microorganisms living in sponges represent a promising source of novel bioactive secondary metabolites, potentially useful in developing new nematicidal and antimicrobial agents. This study focuses on extracting bioactive compounds from endosymbiotic bacteria associated with the marine sponge Hyrtios erect sp. (collected from NIOF Station, Hurghada, Red Sea, Egypt) using various organic solvents. Bacillus sp. was isolated and identified through 16 S rRNA gene sequencing. The biocidal activity of Bacillus gotheilii MSB1 extracts was screened against plant pathogenic bacteria, fungi, and nematodes. The n-butanol extract showed significant potential as a biological fungicide against Alternaria alternata and Fusarium oxysporum. Both n-hexane and ethyl acetate extracts exhibited negative impacts against the plant pathogenic bacteria Erwinia carotovora and Ralstonia solanacearum, whereas the n-butanol extract had a positive effect. Regarding nematicidal activity, ethyl acetate and n-butanol extracts demonstrated in-vitro activity against the root-knot nematode Meloidogyne incognita, which causes serious vegetable crop diseases, but the n-hexane extract showed no positive effects. The findings suggest that bioactive compounds from endosymbiotic bacteria associated with marine sponges, particularly B. gotheilii MSB1, hold significant potential as alternative biological control agents against plant pathogens. The n-butanol extract, in particular, displayed promising biocidal activities against various plant pathogenic fungi, bacteria, and nematodes. These results support further exploration and development of such bioactive compounds as sustainable, environmentally friendly alternatives to synthetic pesticides and fungicides in agricultural practices. [ABSTRACT FROM AUTHOR]

ABSTRACT Sea turtles face various threats to survival, primarily due to human activities, such as bycatch, vessel strikes, pollution, and climate change. Many of these activities can lead to illness or injuries, increasing the risk of infection. Treating infections appropriately and effectively requires knowledge of antimicrobial properties and their ability to eradicate microbes without harm to the sea turtle. Robust pharmacokinetic studies, therefore, are important for appropriate dosing. Herein, we review the studies detailing the pharmacokinetic properties of antimicrobials in sea turtles conducted to date. [ABSTRACT FROM AUTHOR]

There is clearly a need for novel antifungal agents, not only concerning spectrum, but also oral bioavailability, tolerability, and drug-drug interactions. There is growing concern for antifungal resistance for current available antifungals, mainly driven by environmental fungicide use or long-term exposure to antifungals, in the setting of mould-active prophylaxis or for chronic antifungal infections, such as chronic pulmonary aspergillosis. Moreover, the incidence of breakthrough infections is increasing, because of the introduction of (mould-active) prophylaxis (1-4). There is emergence of difficult to treat invasive fungal infections, such as those caused by Lomentospora prolificans, cryptic species of Aspergillus, Scedosporium and Coccidioides. Olorofim (F901318) is the first-in class of the orotomides, a novel antifungal class targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in the biosynthesis of pyrimidines. Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, including azole- and amphotericin-resistant isolates. It lacks activity against yeasts and the Mucorales species. It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes. [ABSTRACT FROM AUTHOR]

An 11-year-old, 4.8 kg, intact male mixed-breed dog was evaluated for a bite wound that had occurred a day prior to consultation. On examination, the patient exhibited signs of early to-late decompensatory shock, hemothorax, pneumothorax, and rib fractures. Initial shock management and resuscitation were performed. After several days of stabilization, exploratory thoracotomy, thoracic wall reconstruction, culture sampling, and antibiotic susceptibility tests were conducted. Empirical antimicrobial treatments were performed while pending culture results. Despite aggressive antimicrobial therapy, the patient had focal seizures and wound dehiscence, presumably due to the worsening of infection and inflammation. Necrotic tissues adjacent to the dehiscence were debrided, and the wound was opened. A previous analysis of wound and blood cultures identified Candida glabrata , and itraconazole was initiated in accordance with the culture results. Successful treatment was achieved, and the wound was closed. The patient remained healthy after 2 months of monitoring. To the best of our knowledge, this was the first case report of systemic candidiasis in a dog secondary to a bite wound diagnosed via blood culture. Additionally, this case highlights successful treatment with itraconazole. [ABSTRACT FROM AUTHOR]

Propionic acid (PPA), an anti-fungal agent and common food additive, has been shown to induce atypical neurodevelopment in mice, accompanied by gastrointestinal dysfunction potentially resulting from gut dysbiosis. A putative association between dietary PPA exposure and gut dysbiosis is suggested but has not been explored directly. Here, we investigated PPA-associated alteration in gut microbial composition that may result in dysbiosis. Using long-read metagenomic sequencing, gut microbiomes of mice fed an untreated (n=9) or PPA-rich (n=13) diet were sequenced to assess differences in microbial composition and bacterial metabolic pathways. Dietary PPA was associated with an increased abundance of notable taxa, including several species of Bacteroides, Prevotella , and Ruminococcus , whose member species have previously been associated with PPA production. Microbiomes of PPA exposed mice also possessed a greater abundance of pathways related to lipid metabolism and steroid hormone biosynthesis. Our findings demonstrate PPA's effect in altering the gut microbiota and associated metabolic pathways. These observed changes highlight how preservatives listed as safe for consumption may affect gut microbiome composition with implications for one's health. [ABSTRACT FROM AUTHOR]

This review examined the current state of knowledge on the modifications of commercial soft lining materials (SLMs) with a variety of antifungal compounds: (i) polyene antibiotics, including nystatin and amphotericin B, (ii) azole drugs, including fluconazole, itraconazole, clotrimazole, ketoconazole, and miconazole, and (iii) antiseptics, including chlorhexidine salts to give them anti-Candida albicans properties. The effect of such modifications on the SLMs' physical properties, such as drug release, water sorption, surface properties, bond strength, tensile strength, and hardness, was also analyzed. In effect, this study provided a unique compilation of research results obtained for numerous properties of SLM modified with antifungal compounds that differ in their chemical structure and mechanism of antifungal action. These results might also be useful for prosthetic dentistry, where SLMs are used to prevent and treat candidiasis, the most common disease among denture wearers. [ABSTRACT FROM AUTHOR]

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents. [ABSTRACT FROM AUTHOR]

Background Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa , at infection sites. Objectives As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. Methods In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems. Results It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1β expression in lung bronchial epithelial cells. Conclusions There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is used for epilepsy and bipolar disorder. It has near‐complete bioavailability and is primarily metabolized by glucuronosyltransferases and mitochondrial oxidation. This case highlights a 79‐year‐old male with bipolar disorder on VPA therapy that started with flucloxacillin for Staphylococcus aureus bacteraemia and exhibited significantly reduced VPA serum levels. During hospitalization, flucloxacillin treatment correlated with a sharp decline of 75% in VPA total serum levels, a novel drug–drug interaction not previously reported. Nonadherence and absorption issues of VPA were ruled out, confirming flucloxacillin's role in reducing VPA levels. Because free‐fraction serum levels of VPA remained within therapeutic range (5–25 mg/L) and our patient's bipolar disorder remained stable at 1000 mg twice daily, a dose increase was not necessary. Previous reports described cytochrome P450 enzyme induction as the mechanism of flucloxacillin lowering serum levels of immunosuppressants and antimycotics. Because only 10% of VPA is metabolized by cytochrome P450 enzymes, this is not plausible for this case. The proposed mechanism for the VPA–flucloxacillin drug–drug interaction is flucloxacillin as inducer of glucuronosyltransferase enzymes via the pregnane X receptor pathway, accelerating VPA metabolism. Because this case showed that free‐fraction serum levels remained within therapeutic range, it underscores the need for free‐fraction VPA monitoring in bipolar disorder and flucloxacillin therapy. When VPA is used for epilepsy, it is advised to consider alternative antibiotics to avoid this interaction. [ABSTRACT FROM AUTHOR]

Candida albicans is an "opportunistic fungal agent" in cancer patients that can become colonized in both mucosal and deep tissues and cause severe infections. Most evidence has shown that C. albicans can enhance the progress of different cancers by several mechanisms such as generating virulence factors, participation in endogenous production of pro-inflammatory mediators, and stimulating a wide range of immune cells in the host. The main idea of this review is to describe a range of Candida-used mechanisms that are important in candidiasis-associated malignant processes and cancer development, particularly breast cancer. This review intends to provide a detailed discussion on different regulatory mechanisms of C. albicans that undoubtedly help to open new therapeutic horizons of cancer therapy in patients with fungal infection. The current therapeutic approach is not fully effective in immunocompromised and cancer patients, and further studies are required to find new products with effective antifungal properties and minimal side effects to increase the susceptibility of opportunistic fungal infections to conventional antifungal agents. So, in this situation, a special therapy should be considered to control the infection and simultaneously have the most therapeutic index on tumor patients. [ABSTRACT FROM AUTHOR]

In this study we separated the chemical components of cork from Quercus variabilis by various solvent extraction and alcoholysis methods. We identified the content and chemical composition of suberin and dichloromethane extract with gas chromatography-mass spectrometry (GC-MS) and analyzed the antifungal effects of different cork extracts against wood-decaying fungi. The results showed that the main structural component of cork, suberin, averaging 36.34% of the total dry weight, exhibited a pronounced inhibitory effect on wood-decaying fungi, compared to the dichloromethane extract. By the end of the entire culture period, the colony diameter of white rot fungi was 5 mm in the 40 mg/mL suberin treatment group, 19 mm for brown rot fungi, both significantly smaller than the control group (90 mm). Hydroxy fatty acids, free fatty acids, and α,ω-diacids may be the key components contributing to the antifungal activity of suberin. The inhibitory mechanism of suberin components on wood-decaying fungi may involve suppressing the respiratory metabolism of the fungi and increasing the permeability of their cell membranes, thereby limiting their normal life activities. [ABSTRACT FROM AUTHOR]

A series of indole-1,4-disubstituted-1,2,3-triazole conjugates were synthesised by click chemistry. The haemolytic properties and cytoprotective activity of all the newly synthesised indole-triazole conjugates were tested in vitro. In addition, molecular docking was performed in silico for the selected conjugates to determine their antibacterial and antifungal properties. The results indicate that indole-triazole derivatives effectively protect human erythrocytes against free radical-induced haemolysis in a structure-dependent manner and that bis-indole-bis-triazole derivatives with alkyl linkers are excellent cytoprotective agents against oxidative haemolysis. The tested series of indole-1,4-disubstituted-1,2,3-triazole conjugates may have an affinity for the active sites of specific protein domains (PDB IDs: 2Q85 and 5V5Z) according to molecular docking studies. [ABSTRACT FROM AUTHOR]

The escalating incidence of Candida spp. infections among individuals with compromised immune systems is attributed to various factors, including broad-spectrum antibiotic usage, common health issues, and inadequate undergarments, requiring novel preventive measures. While the pathogenic mechanisms of Candida spp. infections remain incompletely understood, their virulence attributes and opportunistic nature challenge host defenses. In response, this research study introduces an innovative nanobiotechnological approach employing L-cysteine to develop nontoxic anti- Candida spp. textile materials. Cotton, an ideal material for women's underwear, was functionalized with L-cysteine through an exhaustion procedure following activation with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical. The results demonstrated increased energy dispersive X-ray peaks corresponding to sulfur atoms in the functionalized cotton fabric, confirming that L-cysteine remained attached to the cotton surface even after washing cycles. Moreover, the cotton containing L-cysteine displayed morphology and mechanical properties similar to the nonfunctionalized cotton, indicating that the incorporation of L-cysteine did not impact the cotton properties. In addition, cotton functionalized with L-cysteine exhibited a significant reduction in yeast growth – 87.04 ± 1.90% for Candida albicans and 65.28 ± 3.03% for Candida parapsilosis – highlighting its potential as a class I medical device, particularly for preventing candidiasis in women's medical underwear. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that changes in the frequency of oral microorganisms may play a key role in the development of Alzheimer's disease (AD). However, no research has been conducted on the oral fungal composition in AD-patients. The present study aimed to investigate the changes in the frequency of oral fungal composition, the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals. Materials and methods: In the present analytical cross-sectional study during 12 months, 76 hospitalized patients with AD were matched with 76 individuals without AD. A sterile serum physiology-moistened cotton-tipped swab was used to sample the mouth area. All swabs were cultured on Sabouraud Chloramphenicol Agar. Fungal identified were confirmed through the PCRsequencing techniques. Enzyme activity index (EAI) for important pathogenic factors including proteinase, esterase and hemolysin was measured using relevant protocols. The susceptibility to 8 antifungal agents (nystatin, voriconazole, itraconazole, fluconazole, posaconazole, amphotericin B, 5-fluorocytosine, and caspofungin) against fungal strains obtained from ADpatients was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A4 for yeasts. Results: The results showed that compared to the non-AD individuals, the prevalence of oral fungal composition in AD group was 1.6 times higher. Candida albicans was the most common fungal species isolated from oral swab samples of AD group (n=53, 80%) and non-AD group (n=28, 40%), and the diversity of the oral fungal composition in AD-patients were lower than non-AD individuals. Among the 3 investigated virulence factors, a statistically significant difference was shown in terms of hemolysin activity level between the two studied groups (p<0.05) and the activity level of esterase and proteinase enzymes did not show a significant difference in the two studied groups (p>0.05). The results showed that almost all of the tested isolates were susceptible to nystatin, the most widely prescribed antifungal to treat superficial infections, and only 1.69 % (2/118) of the Candida isolates were resistant to this antifungal drug. Conclusion: Understanding the changes in the frequency of oral fungal composition the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals makes it possible to better understand the etiology of this disease. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans), a common fungal pathogen, poses a significant threat to immunocompromised individuals, particularly due to the emergence of resistance against echinocandins, a primary class of antifungal agents. Yck2 protein, a key regulator of cell wall integrity and signaling pathways in C. albicans, was targeted to overcome this resistance. A virtual screening was used to identify Yck2 inhibitors from marine bacterial compounds. Further re-docking, molecular dynamics simulations, and various analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, free binding energy calculations, and RG-RMSD-based free energy landscape were conducted to evaluate the efficacy and stability of the identified compounds. Among the compounds screened, CMNPD27166 and CMNPD27283 emerged as the most promising candidates, demonstrating superior binding affinities, enhanced stability, and favorable interaction dynamics with Yck2, surpassing both the control and other compounds in efficacy. In contrast, CMNPD19660 and CMNPD24402, while effective, showed lesser potential. These findings highlight the utility of computational drug discovery techniques in identifying and optimizing potential therapeutic agents and suggest that marine-derived molecules could significantly impact the development of novel antifungal therapies. Further experimental validation of the leading candidates, CMNPD27166 and CMNPD27283, is recommended to confirm their potential as effective antifungal agents against echinocandin-resistant C. albicans infections. [ABSTRACT FROM AUTHOR]

This study demonstrates a novel nanostructured drug delivery system utilizing α‐Fe2O3/CuO/CuFe2O4 ternary nanocomposite for effective drug transport in sick tissues. Centella Asiatica plant extract was employed to synthesize the Fe2O3/CuO/CuFe2O4 nanocomposite via sol‐gel auto combustion technique. The structural and morphological characteristics of the nanocomposite were investigated by XRD, FT‐IR, SEM, EDX, and VSM for magnetic properties. The XRD analysis demonstrates the successful synthesis of Fe2O3/CuO/CuFe2O4 nanocomposite with an average crystallite size of 18.393 nm. The antioxidant and antifungal capabilities of this nanocomposite were assessed for its biological activity. A notable inhibitory zone was observed when tested against the Alternaria spp. and Bipolaris sorokiniana fungi. An IC50 value of 109.88 μg/ml was found in the DPPH test, indicating that the nanocomposite exhibited remarkable antioxidant characteristics. Subsequently, metronidazole was encapsulated with a success rate of 55.53 % at pH 1.2, while at pH 7.4 it gained 57.83 %. The drug release of nanocomposite at pH 1.2 after 330 min was 43.41 % and at pH 7.4 after 300 min it was 52.3 %. The results indicate its potential as an excellent candidate for drug delivery. Furthermore, pH was found to be an effective catalyst in the drug loading and release processes. [ABSTRACT FROM AUTHOR]

In recent years, compounds from the Schiff base group have been intensively studied for their biological activities. Accordingly, a series of Schiff bases were synthesized from substituted aromatic aldehydes (5-chlorosalicylaldehyde) and differently substituted aromatic amines and their antimicrobial activities were evaluated. The molecular identity of compounds was confirmed using various spectroscopic techniques, such as IR and NMR spectroscopy and elemental analysis, and the molecular structure of compound 3k was determined by single-crystal X-ray analysis. The antimicrobial activity of 3a–3k compounds was examined in sixteen microorganisms (five species of bacteria and eleven species of fungi) using the microdilution method. Regarding antibacterial activity, a remarkable MIC value (0.0098 mg mL−1) and, therefore, the best activity was displayed against Proteus mirabilis for 3e, which is even stronger than the most frequently used antibiotic medications. 3f showed the best antifungal activity against Microsporum gypseum, which is stronger than standard antimycotic fluconazole, and is also an important result considering that Microsporum gypseum can cause dermatophytosis in both humans and animals. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionFungal keratitis (FK) is a difficult condition to treat, particularly in underdeveloped nations. The study aimed to compare the in vitro activity of chlorhexidine (CHX) and seven antifungal agents against a collection of fungi recovered from FK patients.Seventy-three fungi were collected from patients with FK included in study. The antifungal agents tested were fluconazole, voriconazole, posaconazole, miconazole, natamycin, amphotericin B, and caspofungin. The concentration range for CHX was 1–1024 μg/mL. Assessments of antifungal susceptibility were conducted using the EUCAST broth microdilution reference method.The findings demonstrated the beneficial in vitro inhibition of filamentous and yeast fungi by CHX. CHX demonstrated efficacy against Fusarium spp., Aspergillus spp., Candida spp., S. apiospermum and dematiceous fungi at concentrations of 4–64, 32–64, 4–32, 8, and 4–16 µg/mL respectively. The median MICs and MIC distributions of CHX showed no significant differences among the evaluated spp. (p > 0.05). The most effective antifungal drug was posaconazole, which was followed by voriconazole, caspofungin, and amphotericin B.In situations where access to a range of antifungal medications and microbiological facilities is limited, CHX should be further investigated as a potential treatment for FK. It might be able to treat the condition as an inexpensive topical treatment. [ABSTRACT FROM AUTHOR]

A series of 2,2′‐(1,4‐phenylene)bis(N‐substituted phenylthiazolidine‐4‐amide) derivatives, denoted as (A3–9), were synthesized, and characterized for their potential applications against prostate cancer cells (PC3), and Candida albicans fungi. These compounds incorporate various substituents on the phenyl ring such as 4‐NO2, 3‐NO2, 4‐COCH3, 4‐H, 4‐OCH3, 4‐OCH2CH3, and 4‐Cl. The chemical structures of these derivatives were confirmed by NMR, FTIR, and mass spectroscopy. Biological assays, utilizing the MTT assay for prostate cancer cells (PC3) and the disk diffusion assay for Candida albicans fungi, were conducted to evaluate the bioactivity of these compounds. The results revealed promising cytotoxic and antifungal activities. Specifically, compounds A3 (IC50=69.74±0.96), A4 (IC50=63.64±0.950), and A9 (IC50=57.14±0.88 μg/mL) exhibited notable potency against PC3 cells, while A7 and A8 exhibited considerable antifungal efficacy against Candida albicans with MIC of 312 μg/mL. Moreover, density functional theory (DFT) simulations were used to study electronic properties and reactivity descriptors such as energy gap (Eg), ionization potential (IP), electron affinity (EA), chemical potential (μ), chemical hardness (η), global softness (σ), electronegativity (χ), and electrophilicity (ω) to gain a better understanding of the Structure‐Activity Relationship (SAR). Molecular docking analysis against DNA Gyrase and EGFR tyrosine kinase enzymes revealed strong binding interactions of the investigated molecules within their active sites, making them valuable candidates for further development as therapeutic agents against prostate cancer and fungal infections. POM analysis indicates the presence of two antifungal pharmacophore sites (O1δ−, O2δ−) and (O3δ−, O4δ−), as well as two antitumor pharmacophore sites (O1δ−, NH1δ+) and (O4δ−, NH2δ+). [ABSTRACT FROM AUTHOR]

Green synthesized silver nanoparticles (AgNPs) have received lots of attention due to being used as potential therapeutic agents. For the first time, this research investigated the biosynthesis of silver nanoparticles using the extract of Daphne mucronata seeds, which are rich in phenolic and polyphenolic substances and evaluated their antibacterial, antifungal, and scavenging activities. The process of nanoparticle (NPs) preparation was confirmed using UV–vis spectroscopy with an absorption peak at a wavelength of 440 nm. Dynamic light scattering (DLS) was used to determine the particles' distribution. Fourier‐transform infrared spectroscopy (FTIR) validated the functional groups contributing to the reduction of Ag+ to Ag. Moreover, X‐ray diffraction analysis (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) approved the crystalline nature and spherical shape of the particles with mean and standard deviation of particle size to be 60.25 and 24.88 nm, respectively. The antibacterial, antifungal, and scolicidal activities of AgNPs were studied using disc diffusion against four standard bacteria species and microdilution methods for four Candida strains. The greatest effect of AgNPs with the highest concentration (80 µg/mL) was observed on Staphylococcus aureus (22.26 mm) and the lowest on Pseudomonas aeruginosa (19.07 mm). In the case of Candida fungus, the highest effect of AgNPs was reported for Candida krusei (7.93 µg/mL) and the lowest for Candida albicans (63.49 µg/mL). Also, these nanoparticles were able to register 100% lethality on the Echinococcus granulosus parasite in 15 min at a concentration (80 µg/mL). Therefore, the production of AgNPs as a renewable and cheap material can be effective after performing all the necessary tests as antibacterial, antifungal and antiparasitic agents with the least side effects in biomedical and pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine. Methods: Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay. Results: Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication. Discussion: This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens. [ABSTRACT FROM AUTHOR]

Background: Usually non-pathogenic in immunocompetent individuals, mucormycosis is an aggressive, angio-invasive fungus. It is a rare, opportunistic infection belonging to the zygomycete family. The second wave of COVID-19 saw the emergence of a more dangerous and a potentially deadly invasive fungal sinusitis evolving in rhino-cerebral mucormycosis thus compounding and complicating the pandemic. Alarming and exponential rise in the number of cases of rhino-cerebral mucormycosis in India versus the rest of the world when the treatment protocols essentially remained the same needs to be probed scientifically along with its prompt management. Here an attempt has been made to explore this in the study of 50 cases of rhino-cerebral mucormycosis. This study aims to explore the cause and extension of the disease along with its treatment and outcome in 50 cases of post COVID rhino-cerebral mucormycosis. Results: This is a retrospective cohort study conducted on 50 patients with post COVID-19 invasive mucormycosis of the paranasal sinuses with extension to surrounding structure visiting Otorhinolaryngology department at Acharya Vinoba Bhave Rural Hospital, Wardha. Among 50 patients, 86% males in 4th to 7th decade with mean age of 51.08 years. Large majority had mild–moderate severity on high-resolution computed tomography thorax with 84% having uncontrolled diabetes and 18% newly diagnosed diabetic cases. Seventy-two percent had history of steroid intake for COVID-19 management. Maxillary sinus was most commonly involved sinus in 94% cases while 32% had commonest extra nasal spread hard palate. Seventy-eight percent of the post operated mucormycosis cases are alive with no recurrence, 8% are alive and had recurrence of the disease while 14% resulted in death. Conclusion: Effective management and control of the infection can be achieved with the use of strong antibiotics, oral or systemic antifungal drugs, extensive surgical excision of diseased tissue, and addressing underlying risk factors can effectively manage and control the infection. This approach results in positive outcomes and reduced morbidity compared to the time prior to the COVID-19 pandemic including cases with extensive disease. [ABSTRACT FROM AUTHOR]

Dermatophyte infections of the skin and nails are frequent, but current antimycotics have several drawbacks. In search of new treatments, we looked into the vast array of herbal active agents. Derived from plants, they are sustainable, agreeable for patients, and may have less side effects than traditional antimycotics. In this study, we assessed 43 herbal agents for their effectiveness against Trichophyton rubrum (T. rubrum), Trichophyton benhamiae (T. benhamiae), Trichophyton tonsurans (T. tonsurans), and Microsporum canis (M. canis), four major human dermatophyte pathogens. The antifungal effect was tested by incorporating the agents into agar plates and measuring the dermatophyte growth after 7 days. Against T. rubrum, 16 out of 43 herbal agents showed total inhibition of dermatophyte growth. 14 out of 43 herbal agents inhibited the growth of T. benhamiae completely. 18 out of 43 herbal agents were effective against T. tonsurans. Against M. canis, 15 out of 43 herbal agents showed total growth inhibition. Twelve herbal agents inhibited the growth of all tested dermatophytes completely. This study demonstrates the high antimycotic potential of herbal therapeutics and identified promising candidates for the topical treatment of dermatomycoses. Substances are highly agreeable and should be tolerated well. Some might even provide new options for the systemic treatment of fungal diseases. [ABSTRACT FROM AUTHOR]

AbstractCandida infections, particularly invasive candidiasis, pose a serious global health threat. Candida albicans is the most prevalent species causing candidiasis, and resistance to key antifungal drugs, such as azoles, echinocandins, polyenes, and fluoropyrimidines, has emerged. This growing multidrug resistance (MDR) complicates treatment options, highlighting the need for novel therapeutic approaches. Antifungal peptides (AFPs) are gaining recognition for their potential as new antifungal agents due to their diverse structures and functions. These natural or recombinant peptides can effectively target fungal virulence and viability, making them promising candidates for future antifungal development. This review examines infections caused by Candida species, the limitations of current antifungal treatments, and the therapeutic potential of AFPs. It emphasizes the importance of identifying novel AFP targets and their production for advancing treatment strategies. By discussing the therapeutic development of AFPs, the review aims to draw researchers’ attention to this promising field. The integration of knowledge about AFPs could pave the way for novel antifungal agents with broad-spectrum activity, reduced toxicity, targeted action, and mechanisms that limit resistance in pathogenic fungi, offering significant advancements in antifungal therapeutics. [ABSTRACT FROM AUTHOR]

Parabens are the most prevalent ingredients in cosmetics and personal care products (PCPs). They are colorless and tasteless and exhibit good stability when combined with other components. Because of these unique physicochemical properties, they are extensively used as antimicrobial and antifungal agents. Their release into the aquatic ecosystem poses potential threats to aquatic organisms, including fish. We conducted an electronic search in PubMed (http://www.ncbi. nlm.nih.gov/pubmed) using the search term parabens and fish and sorted 93 articles consisting of methyl paraben (MTP), ethyl paraben (ETP), propyl paraben (PPP), butyl paraben (BTP), and benzyl paraben (BNP) in several fish species. Furthermore, we confined our search to six fish species (common carp, Cyprinus carpio; fathead minnows, Pimephales promelas; Japanese medaka, Oryzias latipes; rainbow trout, Oncorhynchus mykiss; Nile tilapia, Oreochromis niloticus; and zebrafish, Danio rerio) and four common parabens (MTP, ETP, PPP, and BTP) and sorted 48 articles for review. Our search indicates that among all six fish, zebrafish was the most studied fish and the MTP was the most tested paraben in fish. Moreover, depending on the alkyl chain length and linearity, long-chained parabens were more toxic than the parabens with short chains. Parabens can be considered endocrine disruptors (EDs), targeting estrogen-androgen-thyroid-steroidogenesis (EATS) pathways, blocking the development and growth of gametes, and causing intergenerational toxicity to impact the viability of offspring/larvae. Paraben exposure can also induce behavioral changes and nervous system disorders in fish. Although the USEPA and EU limit the use of parabens in cosmetics and pharmaceuticals, their prolonged persistence in the environment may pose an additional health risk to humans. [ABSTRACT FROM AUTHOR]

In the present study, fluconazole (FLU) showed the highest solubility in clove oil and was selected as the oil phase for the FLU-loaded nanoemulsion (FLU-NE). Among the studied cosurfactants, Labrafac was better than ethanol at providing globules with acceptable sizes and a lower polydispersity index (PDI) when Tween 80 was the surfactant. This optimized FLU-NE was thermodynamically stable. Furthermore, FLU-NE stored at 40 ± 2 °C and 75 ± 5% relative humidity for 6 months demonstrated good stability. The FLU-NE was converted to a FLU-loaded nanoemulsion gel (FLU-NEG) using 2% w/v sodium carboxymethyl cellulose. The FLU-NEG was acceptable in terms of visual appearance and spreadability. Rheological studies revealed pseudoplastic behavior for FLU-NEG. The viscosity of FLU-NEG decreased when the applied rpm was increased. FLU-NEG showed greater drug release than that from a FLU-GEL formulation. Furthermore, the FLU release from FLU-NEG followed the Higuchi model. The results from the in vitro antifungal evaluation of FLU-NEG on Candida albicans ATCC 76615 strain confirmed the increase in the antifungal activity of FLU by clove oil. Significant differences were observed in the zones of inhibition produced by FLU-NEG compared to those produced by the blank nanoemulsion gel (B-NEG), fluconazole suspension (FLU-SUS), and nystatin samples. Thus, the increase in the antifungal activity of FLU using clove oil as the oil phase in its nanoemulsion formulation was quite evident from our results. Therefore, the developed FLU-NEG could be considered a potential candidate for further preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Objective: This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients. Methods: We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data. Results: Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949–0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034–47.636)]. Conclusion: While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population. [ABSTRACT FROM AUTHOR]

Fungi (Neolentinus lepideus, Nl, and Trametes versicolor, Tv) impart wood rot, leading to economic and environmental issues. To overcome this issue, toxic chemicals are commonly employed for wood preservation, impacting the environment and human health. Surface coatings based on antimicrobial chitosan (CS) of high molar mass (145 × 105 Da) were tested as wood preservation agents using an innovative strategy involving ultra-pressurizing CS solutions to deposit organic coatings on wood samples. Before coating deposition, the antifungal activity of CS in diluted acetic acid (AcOOH) solutions was evaluated against the rot fungi models Neolentinus lepideus (Nl) and Trametes versicolor (Tv). CS effectively inhibited fungal growth, particularly in solutions with concentrations equal to or higher than 0.125 mg/mL. Wood samples (Eucalyptus sp. and Pinus sp.) were then coated with CS under ultra-pressurization at 70 bar. The polymeric coating deposition on wood was confirmed through X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM) images, and water contact angle measurements. Infrared spectroscopy (FTIR) spectra of the uncoated and coated samples suggested that CS does not penetrate the bulk of the wood samples due to its high molar mass but penetrates in the surface pores, leading to its impregnation in wood samples. Coated and uncoated wood samples were exposed to fungi (Tv and Nl) for 12 weeks. In vivo testing revealed that Tv and Nl fungi did not grow on wood samples coated with CS, whereas the fungi proliferated on uncoated samples. CS of high molar mass has film-forming properties, leading to a thin hydrophobic film on the wood surface (water contact angle of 118°). This effect is mainly attributed to the high molar mass of CS and the hydrogen bonding interactions established between CS chains and cellulose. This hydrophobic film prevents water interaction, resulting in a stable coating with insignificant leaching of CS after the stability test. The CS coating can offer a sustainable strategy to prevent wood degradation, overcoming the disadvantages of toxic chemicals often used as wood preservative agents. [ABSTRACT FROM AUTHOR]