Fluconazole (FLU) exhibits extensive polymorphism and hydrate formation, posing challenges for controlling its solid-state properties and pharmaceutical performance. Here, powder X-ray diffraction (PXRD) and thermal analysis (DSC/TGA) were used to elucidate solid-state transformation pathways and assess the pH-dependent equilibrium solubility of this important antifungal drug. A commercial FLU drug substance marketed in Brazil was identified as a mixture of polymorph 5 (FLU-P5) and FLU monohydrate (FLU-MH). Water-assisted mechanochemistry converted this mixture into phase-pure FLU-MH, whereas dehydration of FLU-MH produced FLU-P5 and melting yielded an amorphous solid (FLU-AM). Time-dependent PXRD showed that freshly prepared FLU-AM crystallizes over hours to days into a mixture of FLU-MH and FLU-P5. Equilibrium solubility was measured at 37 °C after 12 and 24 h in five media (water, buffers pH 4.5-7.2, and 0.1 M HCl). No significant differences were observed between 12 and 24 h of shaking, indicating that equilibrium was reached within 12 h. FLU-MH and FLU-P5 showed comparable equilibrium solubilities in water and three buffered media (average solubility of ∼6.5 g L-1), while solubility in 0.1 M HCl increased by ∼3.85-fold. PXRD of residual solids demonstrated complete solvent-mediated conversion of FLU-P5 to FLU-MH during equilibration, explaining the similar solubilities of the two starting solid forms. Therefore, this study advances the understanding of relationships among FLU solid phases, establishes a route to obtain phase-pure monohydrate, and provides PXRD evidence that FLU-MH forms at 37°C in water and across the physiological pH range from the pharmaceutically relevant polymorph FLU-P5, thereby governing drug solubility under physiologically relevant conditions even when another solid form is initially present.

A 5/6/6-fused diterpenoid cordifolia A (1), a 3,4:12,13-diseco- podocarpane diterpenoid cordifolia B (2), three new 5/6/5 tricyclic diterpenoids with a spiro furan lactone core cordifolias C-E (3-5), two cleistantane diterpenoids cordifolias F-G (6-7), and a known podocarpane analogue 12-hydroxy-13-methylpodocarpa-9,11,13-trien-3-one (8) were obtained from the aerial parts of Strophioblachia glandulosa Pax var. cordifolia. Their structures were identified by spectral analysis including 1D, 2D NMR, HRESIMS data, and single-crystal X-ray diffraction, as well as quantum chemistry calculations. Compounds 1-5, 7 and 8 were assessed for their antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida albicans strains. Compounds 1-5 showed no synergistic antifungal effect, while compounds 7 and 8 exhibited significant synergistic activity. Compound 8 was therefore selected for further mechanistic investigation. Further mechanistic studies revealed that compound 8 combined with FLC exerts synergistic antifungal activity by activating the Hog1 signaling pathway to suppress hyphal formation and morphological transformation of resistant C. albicans.

Candidiasis is caused by Candida parapsilosis and Candida tropicalis emerges due to antifungal resistance and limited therapies. We aim to assess the antifungal activity of Hedychium spicatum essential oil (HSEO), followed by computational analyses to identify potential lead phytochemicals, targeting lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis. GC-MS identified 29 phytoconstituents, with τ-cadinol (17.94%) as the major component. Disc diffusion demonstrated concentration-dependent antifungal activity against C. parapsilosis and C. tropicalis, with inhibition zones of 11.00 ± 0.53 and 10.40 ± 0.36 mm, respectively, at 100% (v/v). Homology models of CYP51 exhibited structural reliability based on Ramachandran and validation metrics. Molecular docking identified cis-γ-bisabolene with the lowest binding energies (-7.6 and -7.9 kcal/mol) against haem-free CYP51 models of C. parapsilosis and C. tropicalis, respectively, through hydrophobic interactions. ADMET predictions indicated favorable oral absorption, Lipinski compliance, minimal CYP450 inhibition risk, and no hepatotoxicity or mutagenicity. MD simulations confirmed stable complexes using RMSD, RMSF, Rg, and SASA profiles. MM-PBSA showed favorable binding energies of -6.02 and -8.05 kJ/mol compared to fluconazole (0.98 and 0.66 kJ/mol). DFT showed comparable HOMO-LUMO gaps (6.216 and 6.176 eV) and global hardness (3.108 and 3.088 eV). Overall, HSEO shows promising antifungal potential, with cis-γ-bisabolene as a lead candidate.

Bioactive peptides from plant sources are promising alternatives to conventional antifungal therapies. Here, we report the isolation and partial characterisation of a low-molecular-weight antifungal peptide (∼2.5 kDa) from Curcuma longa rhizomes. Bioactivity-guided purification yielded a fraction with potent activity against Candida albicans (MIC = 0.7 μg/mL). In silico analysis identified candidate peptides, including fragments from curcumin synthase 1, consistent with the observed mass.1³C NMR revealed signals compatible with carbon environments associated with residues such as tryptophan and serine, typical of membrane-active peptides. Strong synergistic interactions were observed with nystatin and fluconazole (FIC indices of 0.11 and 0.30, respectively). Ultrastructural analyses (SEM/TEM) showed cell wall disruption and cytoplasmic disorganisation, supporting a membrane-targeting mechanism. The peptide also inhibited germ-tube formation at 2 x MIC. These findings highlight a promising plant-derived peptide for antifungal combination therapy.

Esophagitis dissecans superficialis (EDS), also known as sloughing esophagitis, is a rare, benign disorder characterized by superficial sloughing of the esophageal mucosa. Its pathogenesis remains incompletely understood, with several underlying conditions and medication exposures described as potential predisposing factors. We present the case of a 41-year-old woman with an extensive surgical history, including subtotal gastrectomy with Roux-en-Y reconstruction, who presented with chronic upper abdominal pain and bloating. Esophagogastroduodenoscopy demonstrated superficial sloughing of the esophageal mucosa consistent with EDS. Subsequent histopathologic examination confirmed the diagnosis and showed no evidence of fungal infection. Because esophageal candidiasis was initially suspected based on the endoscopic appearance, the patient was empirically treated with fluconazole and continued proton pump inhibitor therapy. Repeat endoscopy six months later demonstrated complete resolution of the esophageal abnormalities. This case highlights EDS in a patient with extensively altered foregut anatomy and illustrates its potential to mimic infectious esophagitis. Although a causal relationship between prior gastric reconstruction and EDS cannot be established, recognizing this entity and correlating endoscopic and histopathologic findings are important for accurate diagnosis.

Plant phenolics represent a prospective source of renewable antifungal drugs, yet the molecular mechanisms underlying their activity within the structurally varied phenolic components of natural products like wood vinegar remain ambiguous. Nine phenolic compounds from corncob (Zea mays) and Areca catechu wood vinegars, encompassing the phenol, guaiacol, syringol, and benzenediol categories were examined by in silico methods. Geometries and global reactivity descriptors were derived using density functional theory at the B3LYP-D3BJ/def2-TZVP/CPCM-(water) level, homolytic O-H bond dissociation enthalpies (BDEs) and phenoxyl-radical spin-density distributions were calculated to evaluate and elucidate radical-scavenging capacity, while consensus lipophilicity (log P) was estimated to assess membrane permeability. To establish the reactivity trend on a quantitative and transferable basis, the dataset was expanded to include 12 para-, meta-, and ortho-substituted phenols (totaling 21 compounds), the O-H bond dissociation energy in the para-series exhibits a linear correlation with the Hammett constant σ+ (ρ ≈ +8.3 kcal mol-1, r = 0.987). Computed bond dissociation energies (BDEs) were compared with experimental literature values (phenol, 83.2 vs 86.7 ± 0.7 kcal mol-1), validating a consistent B3LYP deviation that neutralizes in the relative assessments upon which the analysis depends. The initial O-H bond dissociation energies for the nine natural compounds varied between 73.7 and 83.2 kcal mol-1, with phenol exhibiting the lowest reactivity and the two benzenediols demonstrating the highest reactivity. log P and BDE exhibited statistical independence (r = 0.15), establishing two orthogonal axes of structure-activity, however the Hirshfeld oxygen spin population of the phenoxyl radical showed a strong correlation with BDE (r = 0.911), indicating that spin delocalization is the underlying physical cause of the observed reactivity trend. Docking with Candida albicans sterol 14α-demethylase (CYP51, PDB 5TZ1) revealed phenolic affinities ranging from -5.0 to -7.6 kcal mol-1, which are inferior to the clinical azole fluconazole (-8.4 kcal mol-1) and the native inhibitor VT-1161 (-12.2 kcal mol-1), the affinity correlated with log P (r = -0.76) but not with BDE, suggesting that direct inhibition of CYP51 is at best a secondary factor. The diminished second O-H bond dissociation energies of benzenediols facilitate a quinone redox cascade that, when measured against a peroxyl reference bond, categorizes the phenols into radical-terminating monophenols and redox-cycling propagators. The framework offers a structural justification for the antifungal properties of lignin-derived phenolics at the individual component level and emphasizes the unexploited low-BDE/high-log P area as a focus for enhancement.

Community-acquired fungemia in immunocompetent hosts remains exceptionally rare. Kodamaea ohmeri is an emerging opportunistic yeast pathogen increasingly recognised as a cause of invasive fungal infections, particularly among immunocompromised individuals and in healthcare settings. A 33-year-old previously healthy female farmer presented with severe leptospirosis with multiorgan dysfunction. Blood cultures obtained before central venous catheter insertion grew K. ohmeri, identified by the VITEK 2 YST card and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry. Repeat blood cultures also yielded K. ohmeri, confirming true bloodstream infection. The patient had no conventional risk factors. Antifungal susceptibility testing demonstrated high susceptibility to amphotericin B, voriconazole, and caspofungin, whereas fluconazole showed reduced susceptibility. Due to severe hepatic and renal dysfunction, liposomal amphotericin B was preferred, resulting in rapid clinical improvement and clearance of fungemia. Repeat blood cultures showed no growth, and the patient recovered. A review of the literature identified only 14 previously reported cases of community-acquired K. ohmeri fungemia, most of which occurred in patients with identifiable host risk factors or structural disease. This case presents one of the few reports of primary community-acquired K. ohmeri fungemia in an immunocompetent individual and, to our knowledge, shows the first reported association with severe leptospirosis. K. ohmeri should be considered a potential cause of community-acquired fungemia even in immunocompetent hosts. Accurate species identification, repeated blood culture confirmation, and timely antifungal therapy are critical for favourable outcomes. This case expands the clinical spectrum of K. ohmeri infection and suggests that severe leptospirosis may be a possible predisposing condition.

Background: Respiratory tract candidiasis, primarily caused by Candida species, is a prevalent opportunistic fungal infection in individuals with HIV/AIDS. A high HIV viral load is considered a significant risk factor for developing respiratory fungal infection. This study aimed to identify the yeast species isolated from sputum samples of HIV-positive and HIV-negative adults, determine their antifungal susceptibility patterns, and investigate associated risk factors. Methods: A hospital-based comparative cross-sectional study was conducted from March to May 2022. Sputum samples were collected from 190 HIV-positive and 190 HIV-negative participants. Candida and other yeast species were isolated and identified, followed by antifungal sensitivity testing. Results: Of the 190 specimens from each group, 77 (40.53%) from HIV patients and 12 (6.31%) from HIV-negative participants tested positive for yeasts. Candida albicans was the most prevalent species, found in 52 (67.53%) HIV-positive patients and 12 (100%) HIV-negative patients. This was followed by Nakaseomyces glabratus (15.58%), Pichia kudriavzevii (9.09%), Candida tropicalis (6.49%), and Candida parapsilosis (1.29%) in HIV-positive patients. Notably, all 12 isolates from HIV-negative participants demonstrated 100% sensitivity to all ten tested antifungal drugs. In contrast, isolates from HIV patients showed significant resistance to fluconazole and ketoconazole (32.5% each). High viral load (p < 0.001), dermatophyte infection (p < 0.001), and antiretroviral (ARV) regimen (p = 0.030) were significantly associated with respiratory tract fungal infections in HIV patients. Conclusions: Based on this exploratory study, respiratory mycosis is frequent in HIV-positive patients in Cameroon, and identified fungi show increased resistance to azoles. While these results must be interpreted with care due to the sample size relative to the high national HIV prevalence, they suggest that public health education is needed to improve awareness. These preliminary findings prompt a review by health authorities concerning the use of fluconazole for prophylaxis in HIV-positive patients in Cameroon.

Candidozyma auris (Candida auris) candidemia is a serious healthcare-associated infection with substantial mortality and limited treatment options. We retrospectively evaluated adult patients with C. auris candidemia at a tertiary care center between June 2022 and December 2025 to describe clinical management, microbiological outcomes, antifungal susceptibility, and factors associated with 28-day mortality. The descriptive cohort included 108 patients; mortality status was available for 107. Most patients (92.6%) were in intensive care at candidemia onset, and among evaluable patients, 76.1% had prior C. auris colonisation detected. Twenty-eight-day mortality was 41.1% (44/107). Non-survivors were older and had higher Charlson Comorbidity Index, Pitt bacteremia, and Sequential Organ Failure Assessment (SOFA) scores. Central venous catheter removal was more frequent among survivors (72.7% vs 45.0%; P=.012), although removal timing and time to initiation of effective antifungal therapy did not differ significantly between groups. In multivariable analysis, Charlson Comorbidity Index (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.02-1.44) and SOFA score (aOR, 1.16; 95% CI, 1.05-1.27) were independently associated with 28-day mortality. Resistance rates were 95.1% for fluconazole, 31.2% for amphotericin B, and 1.3% for both anidulafungin and micafungin; multidrug resistance rate was 28.6%, and no isolate met the definition of pandrug resistance. Mortality in C. auris candidemia was mainly associated with baseline comorbidity burden and acute organ dysfunction. Local susceptibility surveillance and early recognition of high-risk patients may support treatment and infection-control strategies.