Drug-repurposing strategies have been widely explored to accelerate the development of new treatments for Chagas disease, leveraging compounds with previously established safety profiles. Among these, azole antifungals have attracted attention due to their inhibitory activity against 14-α-lanosterol demethylase (CYP51), an enzyme also present in Trypanosoma cruzi and essential for its ergosterol biosynthesis. Inhibition of this pathway compromises parasite membrane integrity and function and several azoles, including posaconazole, ravuconazole, and miconazole, have demonstrated significant in vitro trypanocidal activity. In this work, we have synthesized new 1,2,3-triazoles as miconazole analogues using eugenol and its analogues as scaffolds. These compounds were initially evaluated against epimastigote forms of T. cruzi and a benzoyl eugenol-derived triazole 16 (IC50 = 37.1 μM) shown trypanocidal potential close to benznidazole (IC50 = 32.3 μM). This compound was further evaluated against trypomastigote and amastigote forms of T. cruzi, displaying IC50 values of 1.4 μM and 2.9 μM, respectively, whereas benznidazole presented IC50 values of 4.09 μM and 3.07 μM, with selectivity indexes of 110 and 53, respectively, considering healthy neonatal rat cardiomyoblast cell line (H9c2 cells). Docking studies suggested CYP51 as a putative molecular target, with compound 16 adopting a binding mode similar to known azole inhibitors. DFT calculations indicated weaker Fe-heme coordination for the 1,2,3-triazole moiety compared to classical azoles, suggesting that inhibition may depend on additional interactions within the binding site. Consistently, the compounds were inactive against Candida species. This finding suggests a degree of selectivity toward the target pathogens evaluated in this study, however additional investigations are required to confirm this selectivity profile. Given the known risk of human CYP inhibition associated with azole derivatives, this observation may be particularly relevant.

Fungal infections pose a significant health burden in Denmark. Increasing global antifungal use and emerging antifungal resistance underscore the need for ongoing characterization of national prescribing trends to inform antifungal stewardship. Danish Health Data Bank Medstat site was accessed to assess total antifungal dispensing in Denmark from 1996 to 2025 across primary care, secondary care (hospitals), and over-the-counter sectors for both topical and systemic antifungals. Over the 30-year period, national antifungal dispensing patterns shifted substantially, with increased dispensing of azole/corticosteroid combination products in primary care (mean annual change of 0.065 g or ml per 1000 inhabitants/day), and persistent predominance of miconazole in secondary care and over-the-counter settings. Systemic prescribing was dominated by oral terbinafine in primary care and fluconazole in secondary care. Oral terbinafine dispensing in primary care was highest in 2009, while fluconazole dispensing peaked in 2013 in secondary care. Following peaks between 2009 and 2013, dispensing of several systemic antifungals subsequently declined, suggesting evolving prescribing patterns over time. Continued increases in azole/corticosteroid dispensing raises concerns regarding antifungal stewardship. Shifts in systemic antifungal dispensing for terbinafine and fluconazole may reflect changes in demographics, disease incidence (e.g., cancer), treatment guidelines, and clinical practice.

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, remains a global health concern, and conventional therapies struggle to maintain effective drug concentrations at the infection site. Miconazole (MIC)-loaded polymeric nanoparticles (MIC-PNPs) were prepared by nanoprecipitation, and Eudragit E 100 concentration, polyvinyl alcohol concentration, and organic-to-aqueous phase ratio were optimized using Design Expert® software. The optimized nanoparticles showed nanometric size, high zeta potential, and excellent entrapment efficiency. Fourier-transform infrared spectroscopy confirmed component compatibility, X-ray diffraction and differential scanning calorimetry indicated conversion of MIC to an amorphous state, and scanning electron microscopy revealed spherical morphology. MIC-PNPs were incorporated into a Carbopol-934 hydrogel (MIC-PNPG), which was characterized for physical properties, drug content, spreadability, mucoadhesive strength, and viscosity. MIC-PNPs and MIC-PNPG released 68% and 58% of MIC, respectively, over 24 h at pH 4.2, following Korsmeyer-Peppas kinetics. MIC-PNPG showed substantial ex vivo mucoadhesive strength. Antifungal assays confirmed superior activity of MIC-PNPs over free MIC, and antibiofilm studies showed concentration-dependent inhibition and degradation of C. albicans biofilms, with MIC-PNPG outperforming MIC-PNPs and free MIC. The hen's egg test-chorioallantoic membrane assay showed significantly lower irritation for nanoparticle-based formulations than the marketed product. Ex vivo studies demonstrated enhanced drug permeation and vaginal tissue retention of MIC-PNPs. In vivo, treatment significantly reduced infection pathogenicity, supported by histopathological findings. These results suggest MIC-PNPs as a promising candidate warranting further clinical investigation for VVC treatment.

Fungal keratitis (FK) is a sight-threatening corneal infection that leads to corneal blindness. Dematiaceous fungal keratitis (DFK) emerged as the predominant cause of FK, followed by Aspergillus spp. and Fusarium spp. This study aimed the prevalence, species distribution, associated clinical features, risk factors, and antifungal susceptibility for keratitis caused by dematiaceous fungi. A prospective study was conducted on suspected FK patients from June 2023 through November 2025 at PGIMER Chandigarh. The corneal samples were processed for routine mycological investigations, including direct microscopy potassium hydroxide (KOH mount) and culture on SDA (Sabouraud's Dextrose agar), further confirmed by DNA sequencing. Antifungal susceptibility testing (AFST) was performed as per the CLSI (Clinical Laboratory and Standards Institute) broth microdilution method (M38-A2) for a panel of nine drugs, including voriconazole, itraconazole, posaconazole, luliconazole, miconazole, ketoconazole, amphotericin-B, natamycin, and terbinafine. Among 1931 suspected FK patients, 452 were confirmed FK where 75 were DFK and prevalence of DFK was calculated 3.88%. Curvularia spp. was found to be most prevalent (n = 39,52%), followed by Alternaria spp. (n = 9, 12%), Colletotrichum spp. (n = 8,10.66%), and Exserohilum spp. (n = 6, 8%) along with eight other rare genera were isolated. Redness, watering, and a decrease in vision were significantly more common in DFK. Amongst the triazoles, voriconazole showed low minimum inhibitory concentration (MIC) range of 0.03-16 µg/ml. AFST also demonstrated low MICs to luliconazole and terbinafine. The present study showed a prevalence of 3.88% DFK in North India with Curvularia spp. as the predominant causative agent. In vitro susceptibility of voriconazole demonstrated better performance against DFK isolates.

Chromatography remains a cornerstone technique in analyzing chiral compounds. The development and selection of chiral stationary phases （CSPs） are central to achieving high-resolution enantiomeric separation. This study presents a novel regeneration and functionalization strategy for the preparation of high-performance superficially porous particle （SPP）-CSP， offering a promising alternative to conventional fully porous particle （FPP）-CSP. First， bonded phases on the surface of spent chromatographic column silica packing materials were removed using ultraviolet light （λ=254 nm） and hydrogen peroxide solution （3%， mass fraction）， thereby obtaining sub-3 μm regenerated SPP. The regenerated SPP were then amino-functionalized. Subsequently， under mild reaction conditions， carbonyldiimidazole-activated （2-hydroxyethyl）-β-cyclodextrin （HE-β-CD） was bonded onto the surface of the amino-functionalized SPP to prepare the SPP-CSP. For comparative evaluation， a CSP based on 3 μm commercial FPPs was prepared. Additionally， a commercial （2-hydroxypropyl）-β-cyclodextrin （Hp-β-CD） chiral column with identical particle size and structure was selected as a reference. This commercial column was used to investigate the selectivity differences among different cyclodextrin derivatives. The enantioseparation and overall chromatographic performance of the CSPs were systematically evaluated under both supercritical fluid chromatography （SFC） and reversed-phase liquid chromatography （RPLC） modes. The evaluation was performed using ten chiral molecular probes： zopiclone， equol， 2-phenylpropionic acid， dobutamine， flutriafol， miconazole， folic acid， catechin， valacyclovir， and chlorphenamine. Results revealed that， under identical chromatographic conditions， the SPP-CSP consistently outperformed the FPP-CSP in terms of enantiomeric resolution， peak sharpness， theoretical plate number， and retention time efficiency. More importantly， the FPP-CSP exhibited a significant loss in resolution when chromatographic conditions were altered to yield equivalent analysis times. In contrast， the SPP-CSP showed only minor adverse effects on resolution when the flow rate was increased to shorten analysis time， highlighting its inherent suitability for ultrafast separations. Moreover， SFC and RPLC modes displayed complementary chiral recognition ranges. Within the overlapping separation scope of both modes， SFC mode achieved higher enantiomeric resolution and superior chromatographic performance. Notably， under RPLC mode， catechin showed high enantiomeric resolution on both CSPs， underscoring system-dependent selectivity differences. Multiple factors-including mobile phase composition （particularly the additive type）， and the stereochemical structure of the analytes-were found to significantly influence enantioseparation outcomes. Under SFC mode， none of the analytes could be eluted when acetonitrile was used as the mobile phase modifier， whereas alcohols effectively enabled elution， with weaker hydrophobicity correlating to stronger elution strength. Among the alcohols tested， methanol offered distinct advantages over isopropanol by maintaining lower backpressure and superior chromatographic performance without compromising resolution. Under RPLC mode， although isopropanol as a mobile phase component provided higher enantiomeric resolution， it resulted in relatively poorer chromatographic performance and higher column pressure drop. Using acetonitrile offered limited flexibility in adjusting elution strength. In both chromatographic modes， the influence trends of mobile phase additives on enantioseparation performance and overall column performance were generally consistent. Mobile phases with acidic additives were more suitable for analyzing acidic analytes such as 2-phenylpropionic acid and folic acid. Mobile phases with ammonium formate were better suited for analyzing basic analytes like chlorphenamine and flutriafol， as well as analytes with pKa values near 7， such as zopiclone. In contrast， NH3 as an additive yielded unsatisfactory results. Compared with the commercial Hp-β-CD chiral column of the same particle size and structure， the SPP-CSP exhibited different selectivity， which varied with the chromatographic mode. Under RPLC mode， the SPP-CSP showed higher resolution for zopiclone， dobutamine， and folic acid. Under SFC mode， it demonstrated higher resolution for equol， folic acid， and valacyclovir. Despite these advances， the study has certain limitations. To enhance compatibility with mass spectrometric detection， normal-phase mode was not investigated. Additives commonly used in chiral compound analysis， such as triethylamine and ammonium trifluoroacetate， were also not employed. Polar organic solvent mode was not investigated either. Additionally， peak symmetry and theoretical plate numbers on the SPP-CSP were generally inferior to those observed on the commercial Hp-β-CD chiral column across both chromatographic modes.

Kerion celsi is a severe inflammatory form of tinea capitis that is uncommon in adults and may mimic bacterial furunculosis, abscess, or cellulitis, resulting in delayed diagnosis and antibiotic-only treatment. We report a 48-year-old woman with a one-month history of a painful, purulent, crusted lesion on the left temporal and retroauricular scalp, localized alopecia, and ipsilateral periorbital edema. She reported close exposure to 10 cats daily and did not improve after treatment for presumed furunculosis. Potassium hydroxide examination demonstrated fungal elements. Fungal culture and lactophenol cotton blue morphology were consistent with Microsporum canis. Histopathology demonstrated dense suppurative follicular and perifollicular inflammation, follicular destruction, and granulomatous inflammation; fungal organisms were not identified on hematoxylin and eosin staining. The patient received oral griseofulvin, topical miconazole, structured wound care, empirical ciprofloxacin for clinically suspected secondary bacterial infection, and adjunctive intramuscular administration of a human umbilical cord-derived mesenchymal stromal cell conditioned-medium secretome preparation. Periorbital edema markedly decreased by day 2. By day 14, lesion dimensions remained approximately 8 × 5 cm, while pain and pruritus had decreased from 6/10 to 0/10 and exudation, pustulation, crusting, erythema, and scalp edema were substantially reduced. This improvement was temporally associated with the combined regimen. Because several interventions were initiated concurrently, the specific contribution of secretome could not be determined. Systemic antifungal therapy remains the cornerstone of treatment, and the safety and efficacy of secretome in active inflammatory dermatophyte infection require further study.