Search Results (91)

We undertook a preliminary clinical study to compare the efficacy of lime essential oil shampoo with a conventional 2% miconazole/chlorhexidine formulation, both in combination with pulse oral itraconazole, in cats with dermatophytosis caused by M. canis. Sixteen affected cats were randomly assigned to receive either lime essential oil shampoo or a 2% miconazole/chlorhexidine formulation. All cats were bathed twice weekly and received itraconazole (5 mg/kg once daily) using a pulse regimen (1 week for every 2 weeks) for 56 days. Clinical assessments, including cytological, direct hair examinations, Wood’s lamp evaluation, total skin lesion score (TLS), and fungal pathogen score (FPS), were performed on days 0, 28, 42, and 56. Hematological and biochemical analyses were conducted on days 0, 28, and 56. By day 56, no significant differences were observed between groups in the cytological, direct hair examination, or Wood’s lamp results. Both groups had significant reductions in TLS and FPS on days 28, 42, and 56 compared to day 0 (p < 0.05). No cutaneous or systemic adverse effects were observed. These findings suggest that lime essential oil shampoo has clinical efficacy comparable to the conventional formulation and may represent a safe natural alternative for the topical management of feline dermatophytosis. Full article

Hemp seeds (Cannabis sativa L.) are a rich source of phenolic compounds with antioxidant and antimicrobial potential. Still, their genotype-dependent variability and ability to enhance antibiotic efficacy remain insufficiently explored. This study compared three Romanian hemp seed cultivars (Lovrin 110, Silvana, and LV 585) extracted by conventional hydroalcoholic extraction (CE) and ultrasound-assisted extraction (UAE) to evaluate their phenolic composition, antimicrobial effects, and synergistic interactions with amoxicillin and miconazole. HPLC identified genotype- and method-dependent differences, with UAE extracts showing substantially higher levels of epicatechin, quercetin, rosmarinic acid, resveratrol, and ferulic acid. These patterns showed stronger antimicrobial inhibition against Gram-positive and Gram-negative bacteria and yeasts, confirmed by MIC, fold-reduction, and percent enhancement assays. The most pronounced synergy occurred in Streptococcus pyogenes, Staphylococcus aureus, Bacillus cereus, and Candida albicans. PCA revealed two dominant phenolic-activity axes: a rosmarinic/resveratrol/ferulic axis associated with potent inhibition in Escherichia coli and C. albicans, and a quercetin-driven axis linked to Gram-positive bacteria. Overall, UAE extracts displayed superior phenolic enrichment and bioactivity, demonstrating that specific phenolic structures—not total phenolic content—govern antimicrobial performance and antibiotic-enhancing potential in hemp seed extracts. Full article

The emergence of drug-resistant Candida species has created an urgent need for non-toxic molecules that inhibit fungal growth, biofilm development, and hyphal formation. In this study, fifty multi-halogenated indole derivatives were screened against ten Candida species, including azole-resistant C. albicans, C. auris, C. glabrata, and C. parapsilosis. Among them, 4,6-dibromoindole and 5-bromo-4-chloroindole exhibited the strongest antifungal and antibiofilm effects, with minimum inhibitory concentration (MIC) values of 10–50 µg/mL, outperforming ketoconazole and comparable to miconazole. Both di-halogenated indoles markedly inhibited cell aggregation, yeast-to-hyphae transition, and induced reactive oxygen species (ROS) accumulation, contributing to fungicidal activity. Microscopic analyses revealed the disruption of hyphal networks and reduced biofilm biomass. They showed moderate cytotoxicity in human hepatocellular carcinoma (HepG2) cells (median lethal dose, LD₅₀ = 35.5 µg/mL and 75.3 µg/mL) and low phytotoxicity in plant assays. The quantitative structure–activity relationship (QSAR) model identified halogen substitution at C4, C5, and C6 positions as optimal for antifungal activity due to enhanced hydrophobic and electron-withdrawing effects. Together, these findings demonstrate that di-halogenated indoles serve as potent, low-toxicity inhibitors of Candida growth, biofilms, and morphogenesis, providing a promising scaffold for next-generation antifungal agents targeting drug-resistant Candida species. Full article

The epidemiology of vulvovaginal candidiasis (VVC) in Ecuador remains poorly reported and outdated. We therefore conducted a 12-month prospective survey to assess the aetiology and antifungal resistance patterns among symptomatic Ecuadorian patients. VVC diagnosis was confirmed by microscopic examination and culture. Isolates were identified by biochemical and molecular methods. In vitro antifungal susceptibilities to amphotericin B, clotrimazole, fluconazole, itraconazole, miconazole, and nystatin were determined by CLSI methods. Among 195 women, 71 VVC episodes were recorded (36.4%), whereof 56 (28.7%) had acute VVC (AVVC) and 15 (7.7%) had recurrent VVC (RVVC). The predominant species was Candida albicans, isolated in pure culture from 45 AVVC (80.3%) and 9 RVVC patients (60%), and in mixed culture from 7 AVVC (12.5%) and 3 RVVC patients (20%). Candida glabrata and Saccharomyces cerevisiae were also isolated in AVVC and RVVC patients, but Candida parapsilosis and Candida famata were only isolated from AVVC. Fluconazole- and miconazole-resistant C. albicans isolates were recovered from 5 (8.9%) and 24 (42.9%) of 56 AVVC patients, respectively, and from 1 (8.3%) and 5 (41.7%) of 12 RVVC patients, respectively. Fluconazole and miconazole resistance is relevant in Ecuador, emphasising the need for targeted antifungal strategies. Full article

The objective of this study was to investigate the adsorption of 11 azoles (tebuconazole, ketoconazole, econazole, miconazole, fluconazole, clotrimazole, climbazole, flutriafol, epoxiconazole, tiabendazole, and imazalil) on natural and waste-derived sorbents such as ceramsite, perlite, pumice, sawdust, coconut fibers, heavy oil fly ash (HOFA), activated carbon, and silica gel. The results of adsorption efficiency for most sorbents varied depending on the azole compounds and their concentration. The highest adsorption for all tested compounds was obtained for activated carbon and heavy oil fly ash, reaching about 100% in both tested concentrations (0.2 mg L⁻¹ and 0.02 mg L⁻¹). The HOFA material was characterized in terms of elemental analysis (CHNS), confirming the elemental contents of 52% C, 0.65% H, 0.4% N, and 2.3% S. The specific surface area of HOFA was 11.2 m² g⁻¹, and scanning electron microscopy (SEM) results showed the spherical yet porous nature of the particles. Furthermore, the calculated adsorption isotherms demonstrated that for most tested azoles, the Dubinin–Radushkevich (D-R) isotherm best fits the data, with R² = 0.93 or more, which is characteristic of porous carbon materials. The results highlight the significant potential of the tested HOFA sorbent for effectively removing azoles, as the tests performed showed that it was possible to remove these compounds with a concentration of up to 0.2 mg L⁻¹ within an hour. This is particularly important because HOFA is an easily accessible waste material. Furthermore, the adsorption of azoles will not increase the cost of HOFA disposal when using the standard procedures currently applied to this waste. Full article

Background/Objectives: Malassezia pachydermatis is a lipophilic yeast frequently associated with otitis externa and dermatological disorders in companion animals. This study aimed to evaluate the antifungal susceptibility of M. pachydermatis isolates from dogs and cats and to investigate the genomic determinants of reduced susceptibility. Methods: Susceptibility testing of 87 clinical isolates was performed using a modified CLSI broth microdilution method in Sabouraud dextrose broth supplemented with 1% Tween 80. The whole genome of ten representative isolates was sequenced and the genetic factors that are involved in drug resistance were investigated. Results: Ketoconazole, itraconazole, and terbinafine exhibited the highest efficacy, while miconazole and clotrimazole showed reduced activity. Whole genome sequencing revealed single nucleotide polymorphisms (SNPs) in genes that play a key role in the ergosterol biosynthesis pathway, particularly in ERG11 and ERG1. While some specific amino acid substitutions (e.g., K446R in ERG11) were found only in isolates with elevated MIC values, no direct correlation with resistance could be unequivocally established. Conclusions: Genomic analyses also uncovered chromosomal mutations and the heterozygosity of certain isolates, suggesting that complex, multifactorial mechanisms may drive the development of drug resistance. These findings highlight the importance of standardized susceptibility testing and further genomic investigations to promote effective antifungal therapy in veterinary medicine. Full article

Complete dentures (CD) are prone to biofilm formation, particularly by Candida species, which may lead to denture stomatitis (DS). As edentulism remains highly prevalent among the global ageing population, denture-related infections represent a significant public health concern. The novelty of this study lies in integrating the clinical severity of DS with the prevalence, microbial load, and antifungal susceptibility profile of Candida spp., providing new insights into the pathogenesis and therapeutic management of this condition. Biofilm from the CD and palate was seeded for prevalence and microbial load. The identification of strains was confirmed molecularly, and susceptibility to micafungin, nystatin, fluconazole, and miconazole was assessed by the broth microdilution method. Prevalence was shown in percentage, microbial load was analyzed using a generalized linear model test, and susceptibility was assessed using Pearson’s Chi-square test (p < 0.05). Candida albicans was the most prevalent regardless of DS. However, a higher microbial load of C. albicans was observed with increased severity of DS (p = 0.038). Except for Candida tropicalis, the microbial load of the CD was higher than that of the palate. C. tropicalis showed resistance to fluconazole with increased severity of DS (p = 0.004). All strains were susceptible to nystatin and miconazole, and three were resistant to micafungin. The findings suggest that the prevalence of Candida spp. is not a determining factor in the variation in DS severity. Nevertheless, patients with severe inflammation harbor an increased load of C. albicans on both sites. Nystatin and miconazole appear to be effective treatments for DS. Full article

Background: Oral candidiasis is a prevalent opportunistic infection, predominantly caused by Candida albicans (CA), though non-albicans Candida (NAC) species are increasing worldwide. This study aimed to characterize the prevalence of Candida species, evaluate antifungal susceptibility, and identify predisposing risk factors in patients with oral mucosal candidiasis. Methods: A retrospective review of 1286 electronic patient medical records (788 women, 498 men) from 2018 to 2022 was conducted at the Department of Periodontal and Oral Mucosa Diseases, Medical University of Silesia. Swabs from the oral cavity were processed to identify Candida strains by mass spectrometry, followed by drug susceptibility testing for amphotericin B, nystatin, flucytosine, econazole, ketoconazole, miconazole, and fluconazole. Relevant local and systemic predisposing factors were recorded and analyzed statistically. Results: Among 958 patients with positive fungal cultures, CA accounted for 66.79% of isolates, while NAC constituted 33.21%. Multi-strain infections were detected in 8.46% of patients. CA showed lower resistance (<10%) to amphotericin B, nystatin, and flucytosine, but up to 30% resistance to azoles. NAC strains demonstrated elevated resistance rates (>40% for most azoles), with C. krusei exhibiting the highest resistance to the previously mentioned antifungal agents. Key risk factors included wearing removable dentures (p = 0.042) and uncontrolled diabetes mellitus (p = 0.0431). Additional factors, including poor oral hygiene, reduced salivary flow, and immunosuppressive conditions, further increased infection risk. Patients presenting with multiple risk factors were more likely to have multi-strain infections and more severe disease courses. Conclusions: This retrospective analysis highlights the growing prevalence of NAC, rising antifungal resistance (particularly to azoles), and the importance of identifying risk factors, especially denture use and poor glycemic control. Enhanced preventive strategies, robust diagnostic approaches, and optimized antifungal regimens are essential to address this evolving clinical challenge. Full article

The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health. Full article

Background/Objectives: We report the antifungal potential of transition metal-free borophosphate glass-loaded hydrogels (BGHs) with different phosphorus/boron molar ratios (P/B = 2, 1, and 0.5) against Candida species. Candida yeasts pose a significant health risk as they can cause infections, systemic diseases, and even potentially fatal complications in immunocompromised individuals. Methods: The antifungal activity of BGH was evaluated against Candida albicans, Candida tropicalis, Candida krusei, and Candida glabrata using kinetic growth analysis, the agar well diffusion method, the minimum inhibitory concentration, the minimum fungicidal concentration, and scanning electron microscopy. Results: All BGH formulations effectively inhibited yeast growth at various concentrations, with results comparable to commercial miconazole gel (CMG). Hydrogels with P/B ratios of 0.5 and 1 produced larger inhibition zones than CMG, except against C. glabrata. However, BGHs with a P/B ratio of 0.5 at 3% and 5% (w/w) demonstrated relevant antifungal activity, especially against C. albicans and C. tropicalis. Conclusions: These findings highlight the promising antifungal potential of borophosphate glass-based hydrogels, particularly those with high boron content. Their efficacy against multiple Candida species suggests they could serve as an alternative to conventional antifungal agents. Full article

Background/Objectives: Nisin A, an antimicrobial peptide produced by Lactococcus lactis, primarily shows antimicrobial activity against Gram-positive bacteria, with efficacy increased when used in combination with an antimicrobial drug. On the other hand, oral candidiasis, caused by Candida, occurs in immunocompromised patients and requires antifungal therapy. However, antifungal drug-resistant Candida strains are increasing worldwide, leading to serious problems. Methods: To examine the effects of nisin A against Candida species, we investigated the combined effects of nisin A and antifungal drugs on the growth and viability of Candida strains. Results: While nisin A alone had no antifungal effect, together with amphotericin (AMPH), it showed synergistic effects towards C. albicans, as well as the non-albican strains C. glabrata, C tropicalis, and C. parapsilosis in checkerboard assay results. Furthermore, nisin A with miconazole (MCZ) or micafungin (MCFG) demonstrated a synergistic or additive effect on those strains. Cell viability assay results showed that nisin A enhanced the fungicidal activity of AMPH against both C. albicans and C. glabrata. Biofilm reduction assays showed that nisin A with AMPH, MCZ, or MCFG inhibited biofilm activity against C. albicans as compared with each antifungal drug alone. Finally, nisin A with AMPH, MCZ, or MCFG resulted in a reduced minimum inhibitory concentration of those antifungal drugs against clinically isolated C. albicans and C. glabrata.Conclusions: When used in combination with nisin A, the antifungal drug dosage can be lowered, thus helping to prevent adverse side effects and the emergence of drug-resistant oral Candida species. Full article

Failure in the proliferation, recruitment, mobilization, and/or differentiation of oligodendrocyte precursor cells (OPCs) impedes remyelination in central nervous system (CNS) demyelinating diseases. Our group has recently achieved the generation of functional oligodendroglia through direct lineage conversion by expressing Sox10, Olig2, and Zfp536 genes in adult rat adipose tissue-derived stromal cells. The present study aimed to determine whether various repurposed drugs or molecules could enhance the myelinating capacities of these induced OPCs (iOPCs). We report that kainate, benztropine, miconazole, clobetasol, and baclofen promote in vitro iOPCs migration, differentiation, and ensheathing abilities through mechanisms similar to those observed in rat neural stem cell-derived OPCs. This research supports the potential use of iOPCs as they provide an alternative and reliable cell source for testing the effects of in vitro promyelinating repurposed drugs and for assessing the molecular and cellular mechanisms involved in therapeutic strategies for demyelinating diseases. Full article

Infections caused by Malassezia (M.) pachydermatis in dogs are mostly treated with azole antifungals. Excessive use of these drugs is usually associated with an increased incidence of resistant isolates, which can be prevented by combining commonly used antifungals with natural bioactive compounds. The present study aimed at testing the effectiveness of a combination of selected azole derivatives showing low antifungal activity against M. pachydermatis isolates, with plant essential oil components displaying the highest efficacy. Among the four azole antifungals tested (itraconazole, posaconazole, clotrimazole, and miconazole), clotrimazole (a mean MIC of 7.62 μg/mL at 72 h and 7.24 μg/mL at 96 h) and miconazole (a mean MIC of 1.71 μg/mL at 72 h and 2.33 μg/mL at 96 h) exhibited the lowest antifungal efficacy. Out of the four plant essential oil components tested (eugenol, terpinene-4-ol, geraniol, and limonene), eugenol (an average MIC of 378.57 μg/mL at 72 h and 1180 μg/mL at 92 h) showed the highest antifungal activity. The checkerboard method was used to assess the interaction of these agents. The fractional inhibitory concentration index (FICI) values for the combination of clotrimazole with eugenol reached 1.43 at 72 h and 0.70 at 96 h and for the combination of miconazole with eugenol, 1.30 at 72 h and 0.45 at 96 h. A higher effect of the combinations was recorded at 96 h, when the combination of clotrimazole with eugenol showed an additive effect in 66.67% of the isolates, and the combination of miconazole and eugenol brought a synergistic effect in 57.14% of the isolates. The obtained results indicate that eugenol is a suitable agent for enhancing the efficacy of poor azoles against M. pachydermatis. Full article

Clinical and mycological data are essential for the optimal management of patients with Candida vaginitis (CV), particularly in cases of (i) azole-resistant C. albicans vaginitis, (ii) recurrent CV, and (iii) CV in pregnant women. The present retrospective single-center study investigated the antifungal activity of six commonly used antifungals against randomly selected vaginal isolates recovered from 68 pregnant women in Adana, Türkiye, including C. albicans, petite C. glabrata, non-petite C. glabrata, and C. krusei, using the disk diffusion method at pH 4 and 7. Furthermore, the antifungal activities of fluconazole and itraconazole were also assessed using the broth microdilution method. For all isolates, the mean inhibition zone diameters were narrower for itraconazole and ketoconazole and larger for miconazole at pH 4 than pH 7 (p < 0.05). For nystatin, zone diameters were wider in C. albicans and petite C. glabrata at pH 4 (p < 0.001 and p < 0.001). Remarkably, clotrimazole was more active at pH 4 than at pH 7, except against non-petite C. glabrata isolates. Based on the broth microdilution results, the resistance rate was higher at pH 4 than at pH 7 in all isolates. Candida glabrata petite isolates exhibited MIC values 2 to 5 times higher than those of the non-petite isolates for both fluconazole and itraconazole. This study highlights the potent activity of topical antifungals (miconazole, nystatin, and clotrimazole) for the treatment of CV in pregnant women and highlights the need to identify petite and non-petite mutants of vaginal C. glabrata isolates to obtain more reliable data and for antifungal susceptibility testing prior to decision-making. The results of the two antifungal susceptibility methods were compared for C. albicans and C. glabrata isolates, and the reliability of the disk diffusion test was discussed. Full article

Although the mitochondrial genome is an attribute of all eukaryotes, some yeast species (called petite-positive) can replicate without mitochondrial DNA (mtDNA). Strains without mtDNA (known as rho⁻ mutants or petite mutants) are respiration-deficient and require fermentable carbon sources (such as glucose) for their metabolism. However, they are compromised in many aspects of fitness and competitiveness. Nevertheless, a few research groups have reported that some petite mutants of Candida glabrata and Saccharomyces cerevisiae manifested higher levels of tolerance to the antifungal fluconazole than their wild-type (WT) counterparts. In this study, we show that elevated tolerance to two or three out of four tested antifungals is a generic feature of at least five petite-positive species of yeasts including C. glabrata (higher tolerance of petites to clotrimazole and miconazole), S. bayanus (tolerance to clotrimazole, fluconazole, and miconazole), S. cerevisiae (tolerance to clotrimazole and fluconazole), S. paradoxus (tolerance to clotrimazole, fluconazole, and miconazole), and S. pastorianus (tolerance to clotrimazole and fluconazole). Comparing the levels of tolerance to the antifungals in WT and petite mutants was based on measuring the diameters of the zones of inhibition (ZOIs) using disc diffusion assays. The mode of inhibition in the majority of WT strains by all antifungals was fungicidal; most of the rho⁻ mutants manifested fungistatic inhibition. We observed partial (not complete) inhibition in WT, with four different types of ZOI patterns that were species- and antifungal-specific. The partial inhibition was characterised by the presence of antifungal-tolerant colonies within ZOI areas. The inability of these colonies selected from ZOIs to grow on glycerol, as a single source of carbon, proved that they were rho⁻ mutants spontaneously generated in the WT populations. The results on the elevated tolerance of petite strains to antifungals are discussed in terms of the prospective positive selection of respiratory-deficient mutants and the various implications of such selection. Full article