Search Results (372)

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 One Health approach offers an integrative framework to understand infectious threats, environmental factors, antimicrobial resistance (AMR) and how their interactions affect the human–animal–environment interface. This review examines the epidemiology, transmission pathways, and mechanisms of microorganisms of public health importance (bacteria, fungi, parasites, and viruses). It highlights the interconnectedness of ecosystems, where the environment plays a central role in the dissemination of pathogens, driven by climate change, globalization, agricultural intensification, and habitat degradation. AMR is a major concern, driven by the indiscriminate use of pharmaceuticals in human, veterinary, and agricultural settings, horizontal gene transfer through mobile genetic elements, and microbial evolution. The study of different pathogens is of great importance due to their high prevalence in different ecosystems, their virulence, clinical interest, and mortality rates produced. Some of them are ESKAPE bacteria, Candida auris, Plasmodium falciparum, and emerging viruses such as SARS-CoV-2, which present complex transmission dynamics influenced by ecological and health determinants. The review also addresses the effects of climate change on the persistence and geographic spread of pathogens. Successful implementation of the One Health program requires intersectoral policies, integrated surveillance systems, prudent use of antimicrobials and investment in translational science. Coordinating these strategies is essential to limit the spread of pathogens, protect biodiversity, and save global health in the face of the growing threat of infectious diseases. Full article

Background: Infection prevention and control (IPC) in hospitals relies heavily on infection control nurses (ICNs) who manage complex consultations to prevent and control infections. This study evaluated large language models (LLMs) as artificial intelligence (AI) tools to support ICNs in IPC decision-making processes. Our goal is to enhance the efficiency of IPC practices while maintaining the highest standards of safety and accuracy. Methods: A cross-sectional benchmarking study at Queen Mary Hospital, Hong Kong assessed three LLMs—GPT-4.1, DeepSeek V3, and Gemini 2.5 Pro Exp—using 30 clinical infection control scenarios. Each model generated clarifying questions to understand the scenarios before providing IPC recommendations through two prompting methods: an open-ended inquiry and a structured template. Sixteen experts, including senior and junior ICNs and physicians, rated these responses on coherence, conciseness, usefulness and relevance, evidence quality, and actionability (1–10 scale). Quantitative and qualitative analyses assessed AI performance, reliability, and clinical applicability. Results: GPT-4.1 and DeepSeek V3 scored significantly higher on the composite quality scale, with adjusted means (95% CI) of 36.77 (33.98–39.57) and 36.25 (33.45–39.04), respectively, compared with Gemini 2.5 Pro Exp at 33.19 (30.39–35.99) (p < 0.001). GPT-4.1 led in evidence quality, usefulness, and relevance. Gemini 2.5 Pro Exp failed to generate responses in 50% of scenarios under structured prompt conditions. Structured prompting yielded significant improvements, primarily by enhancing evidence quality (p < 0.001). Evaluator background influenced scoring, with doctors rating outputs higher than nurses (38.83 vs. 32.06, p < 0.001). However, a qualitative review revealed critical deficiencies across all models, for example, tuberculosis treatment solely based on a positive acid-fast bacilli (AFB) smear without considering nontuberculous mycobacteria in DeepSeek V3 and providing an impractical and noncommittal response regarding the de-escalation of precautions for Candida auris in Gemini 2.5 Pro Exp. These errors highlight potential safety risks and limited real-world applicability, despite generally positive scores. Conclusions: While GPT-4.1 and DeepSeek V3 deliver useful IPC advice, they are not yet reliable for autonomous use. Critical errors in clinical judgment and practical applicability highlight that LLMs cannot replace the expertise of ICNs. These technologies should serve as adjunct tools to support, rather than automate, clinical decision-making. Full article

Despite the devastating consequences of fungal disease, research struggles to catch up to present needs. This study aims to give a broad perspective on the situation, investigating patterns and distribution of fungal pathogens and monitoring trends of resistance to antifungal drugs, over an 8-year timeframe, at the National Institute of Infectious Diseases “Prof. Dr. Matei Balș” in Bucharest, Romania. Samples were inoculated on Sabouraud or Brilliance Candida Agar media; strains were identified using MALDI-TOF MS; and antifungal sensitivity testing was performed using E-Tests strips, VITEK2 Compact and MICRONAUT-AM automatic systems. Candida albicans, accounting for 42% of the positive samples, was the most common pathogen observed, with only 17% of the isolates being susceptible to all antifungals tested, while it was also predominant and deadly in the ICU. The emerging Candidozyma auris, found in 8% of the candidoses, exhibited a fluconazole resistance rate of 96.3%. Of the Aspergillus fumigatus strains, 35.7% showed resistance to azoles, and 25% to amphotericin B. In the ICU, more than half of A. flavus-, A. fumigatus- or A. niger-related cases culminated in death. Antifungal resistance is not to be treated lightly, as it is still a complex and dynamic threat, with devastating consequences. Full article

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

The emergence of Candida auris as a disheartening fungal pathogen in healthcare settings has prompted urgent re-evaluation of containment and mitigation strategies. This review critically examines the biological persistence, environmental adaptability, and resistance to standard antifungal therapies of the pathogen, particularly regions with limited surveillance infrastructure. Based on regional experiences, such as those in Saudi Arabia and the Middle East in general, the study reveals systemic weaknesses in diagnosis, reporting, and environmental sanitation. Special consideration is paid to the combination of new disinfection technologies, including ultraviolet irradiation systems and hydrogen peroxide vaporisation, with institutional behaviour change strategies. This discussion shows the importance of synchronising technological development with frequent employee contributions and cross-functional planning. It also encourages the international standardisation of diagnostic platforms and the launch of real-time genomic surveillance to reveal evolutionary trends. Finally, the findings justify the shift towards proactive models of infection control that are founded on the resilience of systems and the agility of institutions. This paper is a synthesis of epidemiological patterns, decontamination strategies and behavioural knowledge to contribute to an emerging body of knowledge that can help to fortify healthcare settings against current fungal threats. Full article

Background: Candida auris has emerged as a significant public health threat causing life-threatening systemic infections. Of particular concern is the frequency of multidrug resistance, high transmissibility, and persistence in the environment; thus, there is a need for novel strategies to prevent and treat this infection. We previously generated a “pan-fungal” vaccine candidate, NXT-2, which induces protective immunity against several invasive fungal infections. Methods: In this study, we investigated the efficacy of NXT-2 immunization against systemic C. auris infection in an immunosuppressed murine model and investigated the possible mechanisms by which NXT-2 protection is mediated in vitro. Results: Active immunization afforded significant improvement in survival and reduced morbidity in neutropenic mice challenged intravenously with C. auris compared to controls (48.4% vs. 13.8%). To assess humoral immunity in promoting protection, passive immunization with NXT-2-specific IgG to neutropenic mice prior to the challenge with C. auris resulted in significantly higher survival (42% vs. 0%) and low morbidity compared to controls. Sera from NXT-2-immunized animals inhibited biofilm formation and enhanced opsonophagocytic killing of multiple C. auris clades in vitro. Conclusions: These findings show that immunization with NXT-2 improves survival in C. auris infection and that NXT-2 antibodies promote antifungal activity in vitro and in vivo. These results extend the range of the pan-fungal NXT-2 vaccine to include protection against systemic C. auris-mediated infection and provide a rationale for the development of NXT-2 monoclonal antibodies for the treatment of C. auris infections. Full article

Candida auris has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of C. auris candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in ERG11, E709D in CDR1, A583S in TAC1b, K52N and E1464K in SNQ2, K74E in CIS2, M192I in ERG4, a novel mutation S237T in CRZ1, and variants in GCN5, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in C. auris. These findings underscore the need for further research to understand C. auris resistance pathways and to guide effective clinical management strategies. Full article

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform’s compatibility with clinically approved adjuvants (MPLA and QS-21), modular peptide design, and potential for multi-pathogen applications underscores its translational promise. FM-SNAP exemplifies a next-generation vaccine strategy that is both scalable and adaptable for high-risk immunocompromised populations. Full article

Background/Objectives: Adnexal masses are commonly encountered in the routine practice of gynecologists, and transvaginal ultrasonography is the preferred imaging modality for assessing the masses in size and complexity. There has been a notable lack of focus on comparative studies concerning benign adnexal tumors. This study aimed to define and compare the specific morphological and vascular characteristics of ovarian mature cystic teratomas (MCTs) and endometriomas using transvaginal ultrasound and Doppler analysis. Methods: This retrospective analysis included 93 patients who underwent surgical intervention for benign adnexal masses at the Obstetrics and Gynecology Clinic Narodni Front from 1 January 2020 to 1 January 2022. Morphological parameters included the appearance of tumors, the largest diameter, volume, capsule thickness, and the presence of fluid in the pouch of Douglas. Hemodynamic parameters included the localization and quantity of blood vessels within the mass, Resistance Index (RI), peak systolic velocity (Vmax), and end-diastolic velocity (Vmin) within detectable tumor vessels. Flow was also assessed in the uterine arteries, calculating the AURI (uterine artery RI) on both the tumor and contralateral sides. Results: There were 46 patients with ovarian mature cystic teratomas, as well as 46 patients with endometriomas; 1 patient presented with both tumors. There were significant differences in ultrasonographic morphological appearance between the two groups. MCTs most frequently presented as multilocular solid cysts (51.0%) or unilocular solid cysts with hyperechoic content (20.4%). Conversely, the majority of endometriomas were classified as unilocular cysts with ground-glass echogenicity (45.5%). A significant difference was identified in the RI of intracystic vessels and the RI of the ipsilateral uterine artery (AURI). Endometriomas presented elevated RI values (0.57 vs. 0.54, p = 0.04) and reduced AURI (0.81 vs. 0.83, p = 0.02) compared to teratomas. Conclusions: These findings confirm that specific morphological and Doppler parameters, particularly the RI and AURI, can assist in distinguishing between endometriomas and mature cystic teratomas. This suggests a potential role for Doppler analysis in improving diagnostic precision for common benign adnexal tumors in clinical practice. Full article

Candida species are the primary fungal pathogens of invasive infections associated with high morbidity and mortality. The identification of these microorganisms is critical for therapeutic management and control of hospital infection. Herein, assays targeting the Intergenic Spacer 2 (IGS2) and Internal Transcribed Spacer 1 (ITS1) from the rDNA locus were developed to differentiate Candida species. Based on consensus nucleotide sequences, specific primers and positive controls were designed, and standard PCR and real-time PCR (qPCR) assays were performed. All primers resulted in specific amplification of the molecular targets of each species with no amplifications of the negative template control. Furthermore, the primers were highly specific when tested with a range of fungal DNAs and no cross-reactivity was observed among Candida species. The assays presented a limit of detection (LoD) of 10 copies of positive control per reaction for all specific primers designed. Overall, our results showed that qPCR assays employing primers targeting the regions IGS2 and ITS1 completely differentiated between Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, and Nakazeomyces glabratus, with great accuracy and no amplification of DNA from other fungal species. Full article

This 10-year retrospective observational study (2015–2024) conducted at Al-Amiri Hospital in Kuwait aimed to analyze the epidemiology, species distribution, and key risk factors associated with Candida bloodstream infections. Data were collected on patient demographics and clinical risk factors, and the distribution of Candida species was determined based on isolates recovered from patients with confirmed candidemia. Multivariate logistic regression was performed to identify factors associated with candidemia outcomes. Cases significantly increased from 33 (2015–2016) to 93 (2023–2024), predominantly affecting elderly patients (≥65 years) and intensive care unit (ICU) admissions. A shift in species distribution was observed, with a decline in Candida albicans and a marked increase in Candidozyma auris (formerly Candida auris) and C. parapsilosis. Antifungal susceptibility patterns were species-specific: C. albicans, C. parapsilosis, and C. tropicalis remained highly susceptible to all tested antifungals, while Nakaseomyces glabratus (formerly Candida glabrata) showed fluconazole resistance in 25% of isolates. C. auris exhibited resistance to fluconazole (97%) and variable resistance to echinocandins and voriconazole. Echinocandins retained broad-spectrum activity across most species. Independent risk factors included ICU admission, advanced age, and comorbidities. N. glabratus and C. auris infections were linked to higher mortality. This study highlights the growing candidemia burden in Kuwait, driven by emerging non-albicans Candida (NAC) spp. and related species. Early species identification and susceptibility testing are crucial for effective treatment and improved outcomes, necessitating enhanced infection control and antifungal stewardship. Full article

Candidozyma auris (formerly known as Candida auris) is an emerging multidrug-resistant fungal pathogen that has become increasingly implicated in healthcare-associated infections; however, its involvement in spondylodiscitis is exceedingly rare. We report the case of a 65-year-old Saudi male with multiple comorbidities who presented with altered mental status and was subsequently diagnosed with Candidozyma auris spondylodiscitis and bilateral psoas abscesses. Despite broad-spectrum antifungal therapy and multidisciplinary management, the patient’s condition rapidly deteriorated. This case highlights the significant challenges in diagnosing and managing multidrug-resistant C. auris infections and underscores the need for early suspicion, effective source control, and novel antifungal strategies in high-risk populations. Full article

Candida species commonly secrete aspartic peptidases (Saps), which are virulence factors involved in nutrient acquisition, colonization, tissue invasion, immune evasion and host adaptation. However, the regulation of Sap production remains poorly characterized in emerging, widespread and multidrug-resistant members of the Candida haemulonii clade (C. auris, C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii). This study investigated the influence of temperature, pH and protein substrate on Sap production using bloodstream isolates of the C. haemulonii clade. Sap activity was initially assessed using the enzyme coefficient (Pz) in fungal cells grown on yeast carbon base (YCB) agar supplemented with bovine serum albumin (BSA) to determine optimal conditions for enzymatic production. C. auris and C. duobushaemulonii exhibited the highest Sap activity at 96 h, pH 4.0–5.0, and 37 °C, whereas C. haemulonii and C. haemulonii var. vulnera displayed more variable and isolate-dependent profiles. Sap production was markedly suppressed at pH 6.0. The addition of pepstatin A, an inhibitor of aspartic peptidases, abolished Sap activity and impaired fungal growth in a dose-dependent manner, confirming both the enzymatic identity and its critical role in nitrogen acquisition. Conversely, YCB supplemented with an inorganic nitrogen source (ammonium sulfate) supported fungal growth but did not induce Sap production. To explore substrate specificity, YCB was supplemented with a panel of proteins. Serum albumins (bovine and human) induced the highest Sap production, followed by globulin, gelatin, hemoglobin, collagen and immunoglobulin G, while elastin and mucin elicited the lowest Sap production. Isolate-specific preferences for protein substrates were observed. Finally, fluorometric assays using a Sap-specific fluorogenic peptide substrate confirmed the presence of Sap activity in cell-free supernatants, which was consistently and entirely blocked by pepstatin A. These findings highlight inter- and intraspecies variability in Sap regulation among C. haemulonii clade, stressing the critical roles of substrate availability, pH and temperature in shaping fungal adaptation to host environments. Full article