Search Results (451)

Background/Objectives: Antifungal resistance among filamentous fungi is an increasing global concern with significant implications for clinical management. Herein, we propose a study aiming to investigate in vitro susceptibility patterns and epidemiology of filamentous fungi in Southern Italy, focusing on MIC distributions and resistance trends. Methods: We reported susceptibility results from Aspergillus spp., Fusarium spp., and Scedosporium/Lomentospora spp. clinical isolates, which underwent azoles, echinocandins, and amphotericin B in vitro testing. Results: Aspergillus fumigatus was the most frequently isolated species, showing an alarming increase in reduced susceptibility to amphotericin B (9.1%). The highest MIC ranges for this antifungal drug emerged in the case of A. fumigatus (1–4 mg/L) and A. terreus (2–8 mg/L), while A. flavus (0.5–4 mg/L) and A. niger (0.25–4 mg/L) showed lower values. As regarding azoles, all the Aspergillus spp. strains exhibited variable MIC values, reporting a 0.06–16 mg/L MIC range for itraconazole, 0.125–1 mg/L for voriconazole, and 0.03–1 mg/L for posaconazole. Fusarium solani exhibited high MICs for azoles (8 mg/L) and amphotericin B (2–4 mg/L), while F. oxysporum and F. proliferatum showed lower MICs (0.25–2 mg/L for amphotericin B and a MIC range of 0.5–8 mg/L for posaconazole). Lomentospora prolificans and Scedosporium apiospermum demonstrated multidrug resistance across all tested antifungals, reporting MIC ranges of 4–8 mg/L for amphotericin B, 0.25–16 mg/L for posaconazole, 0.25–8 mg/L for voriconazole, and 0.125–8 for itraconazole. Conclusions: Our data highlight the critical emergence of reduced antifungal susceptibility among filamentous fungi in Southern Italy, underlining the importance of epidemiological surveillance, precise species identification, and optimized susceptibility testing in the case of mould etiology for invasive fungal infections. Full article

Bovine mastitis is a major bioeconomic and animal health challenge in dairy systems and is traditionally managed with intensive antibiotic therapy, contributing to antimicrobial resistance (AMR). This study explored the therapeutic potential of essential oils (EOs) from two native species of the Valdivian temperate rainforest, Laureliopsis philippiana (Tepa; LP_EO) and Drimys winteri (Canelo; DW_EO), against priority mastitis pathogens. Gas Chromatography–Mass Spectrometry (GC–MS) was used to characterize EO composition, and in vitro antibacterial and antifungal activities were evaluated against clinical isolates of Staphylococcus aureus, Streptococcus uberis and the azole-resistant yeast Pichia kudriavzevii by disk diffusion and broth microdilution assays. Both EOs were dominated by monoterpenes; LP_EO was richer in oxygenated monoterpenes (eucalyptol, terpinen-4-ol), whereas DW_EO showed a pinene-rich profile (β-pinene, α-pinene). DW_EO produced significantly larger inhibition zones than LP_EO against S. aureus and P. kudriavzevii and exhibited lower MIC₅₀/MIC₉₀ values for S. aureus, S. uberis and P. kudriavzevii. Notably, DW_EO showed a higher inhibitory activity against P. kudriavzevii with a MIC₉₀ of 4 mg/mL. These findings support DW_EO as a high-potential dual-action phytotherapeutic candidate for developing formulations and complementary tools within sustainable bovine udder health and antimicrobial stewardship frameworks. Full article

Among Candida species, several are major opportunistic fungal pathogens capable of causing a wide spectrum of infections, ranging from superficial mucosal conditions to severe systemic diseases. Their success as human pathogens is largely due to their ability to rapidly adapt to diverse host environments and develop resistance to antifungal agents. Experimental evolution provides a powerful framework for understanding these adaptive processes by observing evolutionary change in real-time. Although most studies rely on in vitro systems and a limited set of Candida species, there is strong evidence that genome plasticity, including aneuploidy, loss of heterozygosity, and copy number variation, plays a central role in driving rapid adaptation. Experimental evolution has also been applied to study the dynamics of antifungal resistance, particularly to azoles, although relatively fewer studies have explored resistance to echinocandins and polyenes. This review summarizes current knowledge on experimental evolution in pathogenic Candida species, with a focus on genome plasticity, adaptation to host-imposed stress, and particularly on the emergence of antifungal resistance. It also identifies critical research gaps, including the need for broader species coverage, investigation of underexplored antifungal classes, and evaluation of combined therapies. A deeper understanding of these dynamics is essential to improve antifungal strategies and counter the growing threat of drug-resistant Candida spp. infections. Full article

Head and neck cancer (HNC) patients frequently experience alterations in the oral environment following radiotherapy, including xerostomia and impaired mucosal integrity, which may favour fungal overgrowth. This study aimed to characterise oral Candida colonisation in radiotherapy-treated HNC patients and compare it with that of healthy individuals. Unstimulated saliva samples from 61 HNC patients and 100 controls were cultured on chromogenic agar, and isolates were identified using API 20C AUX or MALDI-TOF. Salivary flow was measured to quantify xerostomia. A representative subset of isolates (10 per group) underwent antifungal susceptibility testing by disk diffusion according to CLSI/EUCAST criteria. Candida colonisation was significantly higher in HNC patients than in controls (64.6% vs. 20%, p < 0.001), with greater species diversity and increased detection of non-albicans yeasts, including C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. All HNC patients exhibited reduced salivary flow. Azole resistance was more frequent among HNC isolates (26%) than among controls (10%), whereas all isolates remained susceptible to amphotericin B and nystatin. These findings indicate that radiotherapy-associated xerostomia substantially alters the oral mycobiota and underscore the importance of routine species-level identification and antifungal susceptibility testing in HNC patients to guide clinical decision-making. Full article

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC₅₀ values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC₅₀ of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens. Full article

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora infestans, Botrytis cinerea, and Fusarium oxysporum. Compound 3b exhibited exceptional antifungal activity against R. solani, with an EC₅₀ of 2.10 mg/L. Moreover, it substantially inhibited sclerotia germination (81.5% at 9 mg/L) and formation (79.3% at 9 mg/L), surpassing octhilinone. The protective effect on detached rice leaves and rice seedlings was found to be 43.4% and 85.2% at 100 mg/L, respectively, and 64.4% and 89.4% at 200 mg/L. These findings suggest that benzothiazole and benzoxazole selenones represent promising lead compounds for sustainable plant disease management. Full article

Aspergillus fumigatus, a saprophytic fungus, causes aspergillosis, primarily affecting the immunocompromised. The efficacy of triazole antifungals is compromised by resistance that has developed both clinically and environmentally. Widespread agricultural use of similar triazole fungicides selects for resistant genotypes, leading to potential food contamination and compromising treatment. This study assessed the presence of azole-resistant A. fumigatus in minimally processed food items commonly consumed in Brazil. A total of 25 commercial samples, including black pepper, yerba mate, and green coffee beans, were collected from different regions. Forty-two A. fumigatus isolates were recovered and screened for susceptibility to agricultural and clinical triazoles by determining EC₅₀ values for tebuconazole (0.04–0.7 µg/mL), itraconazole (0.06–0.5 µg/mL), and voriconazole (0.07–0.15 µg/mL). Sequence analysis of the CYP51A gene revealed the presence of M172V mutation, none of which are associated with resistance. Microsatellite genotyping indicated high genotypic diversity and genetic relatedness among isolates from different food sources. Although no azole-resistant phenotypes were identified, the consistent recovery of A. fumigatus from products not directly exposed to azole fungicides highlights the need for continued surveillance. Agricultural environments remain critical hotspots for the emergence and dissemination of resistance, reinforcing the importance of integrated One Health strategies in antifungal resistance monitoring. Full article

Subcutaneous mycoses are a heterogeneous group of chronic fungal infections, usually acquired through traumatic inoculation of environmental fungi and particularly severe in immunocompromised and critically ill patients. These infections involve pathogens with marked morphological and physiopathological diversity, resulting in significant diagnostic and therapeutic challenges. Conventional treatment relies on systemic antifungals such as amphotericin B, itraconazole, and other azoles; however, these therapies are often limited by poor tissue penetration, adverse effects, and prolonged treatment regimens, especially in vulnerable patient populations. In this context, nanodrugs have emerged as promising alternatives by improving solubility, stability, bioavailability, and targeted delivery to infection sites. This review conducted a comprehensive literature search in PubMed, SciELO, ScienceDirect, Web of Science, and Scopus, identifying 31 eligible studies that developed and evaluated antifungal nanosystems using in vitro, ex vivo, and/or in vivo models. Quantitative outcomes included minimum inhibitory concentration (MIC), colony-forming units (CFU), inhibition halo diameter, and survival assays. Overall, the evidence indicates that several nanosystems may overcome key pharmacological limitations of conventional antifungals and enhance therapeutic outcomes. Nevertheless, important translational challenges remain, including toxicity, long-term safety, scalability, and regulatory approval, which must be addressed before clinical implementation. Full article

The rising global incidence of Candida parapsilosis infections is increasingly complicated by antifungal resistance, resulting in frequent therapeutic failure. This study investigated the potential of the natural compound catechin to enhance the efficacy of fluconazole through synergistic interaction. We evaluated the susceptibility of C. parapsilosis clinical isolates and a reference strain to combinations of catechin and fluconazole using standardized microbiological assays and molecular techniques. In vivo efficacy was assessed using the Galleria mellonella infection model. Mechanistic studies included the measurement of intracellular reactive oxygen species (ROS) production and plasma membrane permeability. Catechin alone caused growth retardation in all strains. However, the combination of catechin and fluconazole resulted in complete growth inhibition of the reference strain and significant growth reduction in azole-resistant clinical isolates. While the combination slightly increased intracellular ROS production, no significant changes in plasma membrane permeability or membrane potential were observed. Notably, catechin induced the expression of the resistance-associated genes CpTAC1 and CpCDR1B in resistant isolates. In vivo experiments demonstrated that catechin significantly reduced mortality in G. mellonella larvae infected with C. parapsilosis. These findings suggest that catechin is a promising candidate for developing synergistic antifungal therapies against resistant Candida species. Full article

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

This study evaluated the in vitro interaction of 5-fluorouridine (5-FUrd) with antifungal drugs and examined the role of efflux pumps in 5-FUrd resistance. Eleven reference Candida strains and twenty-three clinical C. albicans isolates from gynecological patients were tested. The antifungal activity of 5-FUrd alone and in combination with amphotericin B, fluconazole, voriconazole, caspofungin, and flucytosine was assessed using the checkerboard microdilution method. Efflux pump activity was evaluated using two inhibitors: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and verapamil. 5-FUrd exhibited antifungal activity against both the reference and clinical Candida strains, with MIC values ranging from 0.1 µg/mL to 409.6 µg/mL. The checkerboard assays revealed primarily no interactions in the reference Candida strains, whereas the reference C. albicans and clinical C. albicans isolates showed notable synergy between 5-FUrd and fluconazole, voriconazole, or caspofungin. The efflux pump inhibitors reduced the MICs of 5-FUrd in the resistant strains of C. lusitaniae, C. kefyr, and particularly C. krusei, suggesting efflux-mediated resistance mechanisms. This study highlights the potential of 5-FUrd, alone or combined with azoles or caspofungin, as an adjunct therapy against Candida infections. It also suggests that reduced susceptibility may be linked to efflux pump activity in certain strains. Full article

In the context of evolving antifungal resistance and increasing reports of clinical outbreaks of non-albicans Candida spp. invasive infections, the rapid detection of resistant patterns is of the utmost importance. Currently, an azole-resistant Candida parapsilosis clinical outbreak is ongoing at Pisa University Hospital. Resistant isolates bear both Y132F and S862C amino acid substitutions. Based on the data and isolates retrieved during the clinical outbreak, mass spectrometry was used to investigate the differences between fluconazole-resistant and -susceptible clinical strains directly from yeast colonies isolated from agar culture media. A total of 39 isolates, 16 susceptible and 23 resistant, were included. Spectra were processed following a standardized pipeline. Several supervised machine learning classifiers such as Random Forest, Light Gradient Boosting Machine, and Support Vector Machine, with and without principal component analysis were implemented to discriminate resistant from susceptible isolates. Support Vector Machine with principal component analysis showed the highest sensitivity in detecting fluconazole resistance (100%). Despite these promising results, external prospective validation of the algorithm with a higher number of clinical isolates retrieved from multiple clinical centers is required. Full article

Coccidioides immitis and C. posadasii are the causative agents of coccidioidomycosis (CM) or Valley Fever, endemic to the alkaline deserts of North and South America. Clinical treatment of CM is predominantly limited to the triazole and polyene drug classes. There are limited therapeutic options for the treatment of CM, most commonly requiring prolonged courses of therapy with established antifungal agents such as azoles and Amphotericin B, which often lead to toxicity and drug resistance. Clearly, there is a need to develop novel and better antifungal drugs against CM. This review examines both repurposed and recently discovered compounds in various stages of development for the treatment of CM. Full article

Amphotericin: B (AmpB)-resistant Candida (C.) species, such as C. parapsilosis, are among the most common causes of invasive fungal infections, posing significant challenges in hospital settings. Although AmpB is considered the first-line treatment owing to its broad-spectrum fungicidal activity, its use is hampered by severe side effects and the emergence of acquired resistance, particularly in C. parapsilosis, which exhibits reduced susceptibility to polyene, azole, and echinocandin-based antifungal drugs. Here, we present findings on photodynamic therapy (PDT) that targets the opportunistic fungal pathogens C. parapsilosis and C. albicans via the use of photosensitizers from the iodocyanine and newly developed iodinated Methylene blue families. These compounds contain heavy iodine atoms that increase the production of reactive oxygen species (ROS), the agents responsible for oxidative cellular damage, via the heavy-atom effect, which promotes intersystem crossing (ISC) and triplet-state formation. A strong antifungal effect was observed against AmpB-resistant C. parapsilosis, indicating a correlation between the quantum yield of ROS generation and the photosensitizing efficacy under near-infrared (NIR) light irradiation. The combination of efficient cellular uptake and enhanced ROS generation positions iodinated photosensitizers as promising candidates for the treatment of drug-resistant Candida strains. Full article

Background: In Saudi Arabia, rising multi-drug-resistant (MDR) fungal infections from broad-spectrum antifungal overuse highlight the urgent need for epidemiological and susceptibility research. Methods: This cross-sectional study analyzed fungal isolates from 55 patients with positive blood cultures in a Riyadh tertiary hospital, with identification and antifungal susceptibility tested via the VITEK-2 compact system. Results: Candida albicans and non-albicans Candida (NAC) were isolated from 11 and 38 patients, respectively. In the NAC group, C. glabrata and C. parapsilosis spp. were predominant. C. glabrata exhibited the highest resistance to antifungals. Increased rates of resistance were shown by fluconazole and itraconazole, whereas voriconazole was the most effective azole with the lowest resistance. No evidence of resistance was found against non-azole antifungals. A single case of triple resistance to ketoconazole, fluconazole, and itraconazole was observed in C. parapsilosis. A single isolate of C. albicans was resistant to all tested azoles. A rare instance of coinfection with C. glabrata and C. albicans was identified in a single male patient with a dual-resistance pattern against posaconazole and itraconazole. Conclusions: The high prevalence of NAC, including tolerant isolates of C. parapsilosis and C. glabrata, along with multi-azole-resistant C. albicans and unique coinfection scenarios, urgently requires robust antifungal resistance surveillance. Full article