Search Results (23)

Background: Community-onset fungemia is a clinically significant syndrome frequently linked to recent healthcare exposure and significant morbidity and mortality. Methods: We performed a 21-year, single-centre retrospective cohort of consecutive yeast bloodstream infections diagnosed at the Emergency Department (2004–2024). Clinical/epidemiological data, species identification (MALDI-TOF MS), antifungal susceptibility (CLSI M27; Sensititre YO10), and whole-genome sequencing (WGS) were analyzed. Results: Forty-eight episodes (51 isolates) were included; 56.3% were male, median age 74 years (IQR 63–82). Acquisition was healthcare-associated in 38/48 (79.2%). Sources were unknown (36.7%), abdominal (22.4%), urological (22.4%), catheter-related (14.3%), and 2.1% was attributed to a cardiovascular and a joint focus; 18.8% were polymicrobial. Crude mortality was 20.8% at 7 days (10/48) and 29.2% at 30 days (14/48). Species distribution: Candida albicans 41.2%, Nakaseomyces glabratus 27.5%, Candida parapsilosis 11.8%, Candida tropicalis 11.8%, Pichia kudriavzevii 3.9%, Clavispora lusitaniae 1.9%, and Candida orthopsilosis 1.9%. No isolate was resistant to anidulafungin, micafungin, or amphotericin B; one N. glabratus showed reduced susceptibility to caspofungin. Azole resistance was observed in one C. albicans and one N. glabratus isolate. WGS (44 isolates) confirmed MALDI-TOF identifications and characterized resistance markers. All 12 sequenced N. glabratus carried ERG2 I207V, PDR15/PDH1 E839D, and PDR1 V91I/L98S. Notable cases included one N. glabratus caspofungin-intermediate with FKS2 F659C, N. glabratus fluconazole-resistant with multiple PDR1 substitutions including a unique novel G857V, and C. albicans fluconazole-resistant harbouring alterations in MRR1/MRR2, CDR1, and ERG11. Conclusions: In this 21-year cohort, community-onset fungemia was predominantly healthcare-associated, with C. albicans as the predominant species, followed by N. glabratus. Crude mortality reached 29.2% at 30 days. Echinocandin resistance was not observed; azole resistance was uncommon. WGS provided precise speciation and actionable insight into resistance mechanisms, including a putatively novel PDR1 G857V in N. glabratus. Full article

Invasive candidiasis (IC) is a life-threatening fungal infection predominantly affecting critically ill patients in intensive care units (ICUs). Despite advances in antifungal therapies, IC remains a diagnostic and therapeutic challenge, with a mortality rate exceeding 40%. The current reliance on blood cultures as the diagnostic gold standard is limited by low sensitivity and prolonged turnaround times, often delaying effective treatment. This often leads to the overuse of empirical antifungal therapies, increasing resistance, healthcare costs, and inconsistent outcomes. To address these issues, this paper introduces a five-step diagnostic strategy developed by an expert panel to optimise IC diagnosis and management. The strategy integrates predictive risk scores, biomarkers, and antifungal susceptibility testing to streamline diagnosis, identify high-risk patients, and promote antifungal stewardship. It also addresses barriers such as resource disparities and variability in clinical practices, offering a practical, standardised strategy for ICUs in the UK and Ireland. The clinical utility of this approach is highlighted through two patient cases. One describes the safe discontinuation of antifungal therapy after a negative (1,3)-β-D-glucan (BDG) assay ruled out IC, reducing unnecessary treatment and adverse effects. The other showcases the use of rapid in-house antifungal susceptibility testing to precisely tailor therapy for a patient with Nakaseomyces glabratus, ensuring effective treatment and preventing resistance. This pragmatic five-step guide simplifies and standardises IC diagnosis, aiming to lower mortality, optimise therapies, and promote judicious antifungal use. Full article

(1) Background: Fungal infections of amniotic fluid, especially those caused by Candida spp., are rare but clinically important, as they can be correlated with preterm birth and poor neonatal outcomes. The aim of this study was to assess the antifungal susceptibility of Candida spp. isolated from amniotic fluid using an MIC (minimum inhibitory concentration)-based assay. (2) Methods: Forty consecutive, exploratory Candida isolates were identified from amniotic fluid samples at the “Cuza Vodă” Clinical Hospital of Obstetrics and Gynecology, Iași, and were analyzed successively using Sabouraud agar, the VITEK^® 2 Compact system, and real-time PCR (RT-PCR). (3) Results: C. albicans was the most abundant species (67.5%), followed by Pichia kudriavzevii, Nakaseomyces glabratus, C. parapsilosis, and C. dubliniensis. Fluconazole resistance was observed in two C. albicans isolates, emphasizing the clinical importance of routine antifungal susceptibility testing, and all C. albicans isolates were resistant to micafungin, while amphotericin B remained effective against all isolates. RT-PCR confirmed the presence of C. albicans DNA. (4) Conclusions: The detection of resistant Candida strains highlights the importance of conducting assessments at the species level, which could help clinicians to ensure better antifungal stewardship. Full article

The rise in antifungal resistance among Candida species has prompted the search for alternative therapies, including plant-derived lectins with antimicrobial properties. This study evaluated the antifungal activity of Microgramma vacciniola frond lectin (MvFL) against clinically relevant Candida species and Nakaseomyces glabratus. MvFL exhibited fungistatic activity, with the lowest minimum inhibitory concentrations (MICs) of 0.625 μg/mL for N. glabratus and 1.25 μg/mL for Candida krusei. The minimal fungicidal concentrations (MFC) were not detected, indicating they are above 80 µg/mL. MvFL significantly reduced N. glabratus proliferation, disrupted lysosomal integrity, and affected mitochondrial membrane potential, indicating interference with key cellular processes. MvFL showed minimal activity against biofilm formation, only reducing Candida tropicalis biofilms at a subinhibitory concentration. Combination assays revealed additive or synergistic effects with fluconazole for C. krusei, C. tropicalis, and notably Candida parapsilosis, while antagonism was observed against Candida albicans and N. glabratus. These findings underscore the species-specific nature of lectin-drug interactions and the importance of evaluating such combinations carefully. Overall, MvFL demonstrates significant antifungal potential, particularly as an adjuvant to existing treatments. Its ability to inhibit growth and disrupt cellular function in yeasts supports the development of plant lectins as novel, safer antifungal agents in response to the growing challenge of antifungal resistance. 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

The continuous increase in microbial resistance to therapeutic agents has become one of the greatest challenges to global health. In this context, the present study investigated the bioactivity of 25 chroman-4-one and homoisoflavonoid derivatives—17 of which are novel—against pathogenic microorganisms, including Staphylococcus epidermidis, Pseudomonas aeruginosa, Salmonella enteritidis, Candida albicans, C. tropicalis, Nakaseomyces glabratus (formerly C. glabrata), Aspergillus flavus, and Penicillium citrinum. Antimicrobial assay was performed using the microdilution technique in 96-well microplates to determine the minimum inhibitory concentration (MIC). Thirteen compounds exhibited antimicrobial activity, with compounds 1, 2, and 21 demonstrating greater potency than the positive control, especially against Candida species. Molecular modeling suggested distinct mechanisms of action in Candida albicans: 1 potentially inhibits cysteine synthase, while 2 and 21 possibly target HOG1 kinase and FBA1, key proteins in fungal virulence and survival. Our findings indicated that the addition of alkyl or aryl carbon chains at the hydroxyl group at position 7 reduces antimicrobial activity, whereas the presence of methoxy substituents at the meta position of ring B in homoisoflavonoids enhances bioactivity. These findings highlight key structural features of these compound classes, which may aid in the development of new bioactive agents against pathogenic microorganisms. Full article

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

Public health in a densely populated city is inextricably linked to the state of the urban environment. The microclimate, the condition of water sources and sanitary well-being are just some of the many environmental factors that have a strong influence on people’s health. The presence of urban green spaces and various birds in cities is extremely important, also to create a more favorable psychological atmosphere for the people who live and/or work there. At the same time, it should not be forgotten that the feces of synanthropic birds are a favorable environment for various potentially pathogenic species of microorganisms, including yeasts of the genus Candida. Here, we investigated the culturable, potentially pathogenic ascomycetous yeast microbiome in the fresh and dry feces of five synanthropic birds (Rock Pigeon, European Starling, White Wagtail, Great Tit and House Sparrow). The samples were collected in spring (May 2024). In total, 48 Rock Pigeon, 47 European Starling, 38 White Wagtail, 32 Great Tit and 30 House Sparrow droppings were collected and analyzed. The selective medium Brilliance Candida Agar was used for cultivation. A total of 638 strains were isolated belonging to 9 yeast species (Arxiozyma bovina, Candida albicans, Nakaseomyces glabratus, Clavispora lusitaniae, C. tropicalis, C. parapsilosis, Pichia kudriavzevii, Debaryomyces hansenii and D. fabryi). All detected yeast species were molecularly identified using the ITS rDNA region. The microbiome of potential pathogens in fresh feces proved to be significantly host-dependent. Most pathogenic yeasts (7 species)—A. bovina, C. albicans, N. glabratus, Cl. lusitaniae, C. tropicalis, C. parapsilosis and P. kudriavzevii—were only detected in fresh feces from pigeons. This list contains five out of six ascomycetous species from the list of critical, high and medium-important yeast pathogens published in the World Health Organization fungal list. Of the potentially pathogenic yeasts, two species were observed in the dry droppings of various birds: C. parapsilosis and P. kudriavzevii. No significant differences in the diversity of culturable pathogens in dry droppings were observed between the different hosts. Fresh droppings from synanthropic birds, especially pigeons (and to a lesser extent dry droppings), therefore pose a health risk. In this study, we did not find any feces from synanthropic birds in which potentially pathogenic ascomycetous yeasts were not detected. To maintain the sanitary safety and well-being of citizens, it is very important to regulate the number of synanthropic birds (primarily pigeons), especially in sensitive areas such as playgrounds, hospital territories, etc. Full article

Candidiasis is a major fungal infection worldwide, with invasive forms linked to high morbidity and mortality. The emergence of azole resistance in Candida parapsilosis causing candidemia led us to examine the epidemiology and antifungal susceptibility of Candida species at the University Hospital of Liège between January 2017 and December 2023. A total of 916 isolates from blood or sterile body fluids, tissues, and abscesses were analyzed. Species identification was performed using MALDI-TOF MS and antifungal susceptibility testing via Sensititre YO10 AST was interpreted according to the CLSI guidelines. Candida albicans remained the predominant species (56%), followed by Nakaseomyces glabratus (19%), Candida parapsilosis (8%), and Candida tropicalis (7%). No significant shift toward non-albicans Candida species (NAC) was observed even during the COVID-19 pandemic, supporting the use of narrow-spectrum empirical therapy in selected patients. Fluconazole susceptibility was high in C. albicans (98.8%), whereas N. glabratus and C. tropicalis showed high resistance rates with 10.1% and 16.9%, respectively. C. parapsilosis showed stable fluconazole susceptibility across the study period. Echinocandins demonstrated excellent activity (95.6–100%), and amphotericin B was effective against nearly all isolates. This seven-year surveillance at the University Hospital of Liège confirms that while C. albicans remains the predominant and highly susceptible species, rising azole resistance in non-albicans Candida—particularly N. glabratus and C. tropicalis—highlights the critical need for ongoing local epidemiological monitoring to guide effective and targeted antifungal therapy. Full article

Nakaseomyces glabratus is an opportunistic fungal pathogen that primarily affects immunocompromised individuals. Unlike other Candida species, N. glabratus exhibits nondimorphic blastoconidial morphology and a haploid genome. It is a leading cause of both superficial (oral, esophageal, vaginal, or urinary) and systemic candidiasis. In this study, we evaluated 47 clinical isolates from Central Bulgaria (Plovdiv) and 1 wild strain isolated from the gut of the beetle Oxythyrea funesta (Coleoptera: Cetoniinae) collected in Sofia, Bulgaria. Growth was observed across a pH range of 3 to 9. The strains were assessed for the production of lipases, esterases, and proteases—enzymes associated with pathogenicity—and their relationship to virulence. Biofilm formation and exopolysaccharide production were also measured, with all strains showing similar profiles. No competitive inhibition of N. glabratus was observed against C. parapsilosis. All isolates exhibited resistance to micafungin, while resistance to both micafungin and anidulafungin was observed in 21 isolates (44%). These findings provide insight into the biochemical characteristics of N. glabratus populations from Southeast Europe, contributing to a better understanding of strain behavior under controlled laboratory conditions and addressing the gap in data on this species in the region. Full article

With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels. Full article

Coinfection rates of candidiasis in patients affected by COVID-19 had a significantly increase during the sanitary contingency. The objective of this scoping review is to analyze the available scientific evidence around the coinfection of invasive candidiasis in hospitalized patients with severe COVID-19 disease. Online databases such as PubMed, EBSCO, SciFinder, Scopus, and SciELO were used to analyze the different scientific studies published from January 2020 to December 2022, selecting 48 publications that reported comorbidity between invasive candidiasis and COVID-19 as a study variable. Based on the PRISMA-ScR extension for scoping reviews, we identified more than half of the publications (57%) as observational, descriptive, and analytic studies, while 43% were systematic reviews. Overall, up to 169,468 adult patients admitted to the intensive care unit were examined. Coinfection was due mainly to Candida albicans (75%), but some more species were reported such as Meyerozyma parapsilosis (formerly Candida parapsilosis); Meyerozyma guilliermondii (formerly Candida guilliermondii); Nakaseomyces glabratus (formerly Candida glabrata); Candida tropicalis; Candida dubliniensis; Clavispora lusitaniae (formerly Candida lusitaniae); and Pichia kudriavzevii (formerly Candida krusei). We concluded that patients infected by SARS-CoV-2 had a higher incidence of fungal coinfections, thus increasing the mortality rate, disease severity, and length of hospital stay in the intensive care unit. Full article

Nakaseomyces glabratus is a medically important fungal pathogen responsible for various opportunistic, life-threatening, and fatal infections, mainly among immunodepressed patients worldwide. Herein, genotypes identified in Central Poland by multilocus sequence typing (MLST) are presented. Along with the genotyping, drug susceptibility was performed. The research was conducted on 30 non-redundant clinical strains, and 15 distinct sequence types (STs) were identified, including three novel STs: ST212, ST213, and ST214. The most prevalent sequence types were ST3, ST6, and ST10. Antifungal susceptibility testing revealed varied resistance rates to azoles, with fluconazole susceptibility at 16.7% and high susceptibility to amphotericin B. No correlation between ST and antifungals MIC were found. The study findings highlight the genetic diversity of N. glabratus in Central Poland and the role of surveillance and research to elucidate antifungals resistance and molecular epidemiology of N. glabratus. Full article

The rising antifungal resistance in Nakaseomyces glabratus, especially to azole drugs like fluconazole, itraconazole, and voriconazole, presents a significant clinical challenge. Plant-derived compounds with synergistic antifungal effects offer a promising solution. Fruitless wolfberry bud tea, rich in flavonoids from a Lycium barbarum L. hybrid, shows potential but is underexplored in antifungal therapies. This study assessed FWE’s antifungal efficacy alone and with azoles against resistant N. glabratus isolates, exploring mechanisms like efflux pump inhibition and gene expression changes. A total of 52 clinical isolates were tested. Fruitless wolfberry bud tea was methanol-extracted (FWE) and lyophilized. Antifungal susceptibility was evaluated using broth microdilution, and synergistic effects were analyzed with checkerboard assays. Growth inhibition, rhodamine 6G efflux, and qRT-PCR for resistance-related genes were conducted. FWE demonstrated inhibitory activity with MICs ranging from 16 to 32 μg/mL. When combined with ITR or VRC, synergistic or additive effects were observed, reducing MICs by 2–8-fold. FWE + VRC exhibited synergy (FICI ≤ 0.5) in 50% of isolates, while FWE + ITR showed synergy in 37.5%. Efflux pump activity, measured by rhodamine 6G, significantly decreased in combination groups (11.4–14.6%) compared to monotherapy (17.3–17.5%). qRT-PCR indicated downregulation of CgCDR1, CgERG11, and CgPDR1 in FWE-treated Cg 1 isolate, with greater suppression in combination groups. FWE might boost the bacteriostatic impact of azole antifungal drugs by blocking efflux pumps and altering the expression of resistance genes. This study identifies FWE as a potent adjuvant to overcome cross-resistance, supporting its inclusion in antifungal strategies. Further research to identify bioactive compounds in FWE and in vivo validation is necessary for clinical application. Full article

The Candida species cell wall plays a pivotal role as a structural and functional barrier against external aggressors and as an intermediary in host–pathogen interactions. Candida species exhibit unique adaptations in their cell wall composition, with varying proportions of chitin, mannans, and β-glucans influenced by the environmental conditions and the morphological states. These components not only maintain cellular viability under osmotic, thermal, and chemical stress, but also serve as the key targets for novel antifungal strategies. MAPK signaling pathways, like the cell wall integrity pathway and the high-osmolarity glycerol pathway, play a crucial role in responding to cell wall stressors. Due to the rise of antifungal resistance and its clinical challenges, there is a need to identify new antifungal targets. This review discusses the recent advances in understanding the mechanisms underlying cell wall integrity, their impact on antifungal resistance and virulence, and their potential as therapeutic targets of C. albicans, N. glabratus, and C. auris. Full article