Candida auris-a systematic review to inform the world health organization fungal priority pathogens list.

The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.

Influence of Major Polyphenols on the Anti-Candida Activity of Eugenia uniflora Leaves: Isolation, LC-ESI-HRMS/MS Characterization and In Vitro Evaluation.

The content of chemical constituents in Eugenia uniflora leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of E. uniflora. In addition, the anti-Candida activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex® LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS2) and subjected to the microdilution method in 96-well plates against strains of C. albicans, C. auris, and C. glabrata. Myricitrin (93.89%; w/w; m/z 463.0876), gallic acid (99.9%; w/w; m/z 169.0142), and ellagic acid (94.2%; w/w; m/z 300.9988) were recovered. The polyphenolic fraction (62.67% (w/w) myricitrin) and the ellagic fraction (67.86% (w/w) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 µg/mL), suggesting an association between the majority constituents and the antifungal response of E. uniflora derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.

Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species.

Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.

Synergistic and potential antifungal properties of tailored, one pot multicomponent monoterpenes co-delivered with fluconazole encapsulated nanostructure lipid carrier.

Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.

A novel diterpenic derivative produced by Streptomyces chrestomyceticus ADP4 is a potent inhibitor of biofilm and virulence factors in Candida albicans and C. auris.

AIM: Isolation, identification, structural and functional characterization of potent anti-Candida compound with specific antagonistic activities against significant human pathogens, Candida albicans and C. auris. METHODS AND RESULTS: The compound (55B3) was purified from the metabolites produced by Streptomyces chrestomyceticus ADP4 by employing column chromatography. The structure of 55B3 was determined from the analyses of spectral data that included LCMS, nuclear magnetic resonance, FTIR, and UV spectroscopies. It was identified as a novel derivative of diterpenic aromatic acid, 3-(dictyotin-11'-oate-15'α, 19'ß-olide)-4-(dictyotin-11'-oate-15″α, 19″ß-olide)-protocatechoic acid. The compound displayed potent antifungal and anti-biofilm activities against C. albicans ATCC 10231 (Minimum Inhibitory Concentration, MIC90:14.94 ± 0.17 µgmL-1 and MBIC90: 16.03 ± 1.1 µgmL-1) and against C. auris CBS 12372 (MIC90: 21.75 ± 1.5 µgmL-1 and Minimum Biofilm Inhibitory Concentration, MBIC90: 18.38 ± 1.78 µgmL-1). Further, pronounced inhibition of important virulence attributes of Candida spp., e.g. yeast-to-hyphae transition, secretory aspartyl proteinase and phospholipase B by 55B3 was noted at subinhibitory concentrations. A plausible mechanism of anti-Candida action of the compound appeared to be the inhibition of ergosterol biosynthesis, which was inhibited by 64 ± 3% at the MIC90 value. The non-cytotoxic attribute of the compound was noted in the liver cell line (HepG2 cells). CONCLUSION: The present work led to the discovery of a novel diterpenic derivative produced by S. chrestomyceticus ADP4. The compound displayed potent anti-Candida activity, particularly against the two most significant human pathogens, C. albicans and C. auris, which underlined its significance as a potential drug candidate for infections involving these pathogens.

Emergence of the novel sixth Candida auris Clade VI in Bangladesh.

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.

Candida parapsilosis candidemia in children admitted to a tertiary hospital in Turkey: clinical features and antifungal susceptibility.

In recent years, the incidence and drug resistance of Candida parapsilosis have increased. Our study aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. Two hundred pediatric patients with C. parapsilosis candidemia were included in the study between 1 January 2010 and 1 August 2023. Clinical samples were evaluated on a BACTEC-FX-40 automatic blood culture device (Becton Dickinson, USA). Yeast isolates were identified to the species level via identification cards (YST) using the VITEK 2 Compact (bioMeriéux, France) system. Antifungal susceptibility was performed using antifungal cell cards (AST-YST01). Approval for the study was received from the "University Faculty of Medicine" Hospital Clinical Research Ethics Committee. Non-catheter candidemia was detected in 127 (63.5%) patients, and catheter-related candidemia was detected in 73 (36.5%) patients. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care unit stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy. We think that our study can provide important information about the clinical profiles, distributions, susceptibility profiles, and control of antifungal resistance of C. parapsilosis isolates. IMPORTANCE: It has been observed that the frequency and antifungal resistance of Candida parapsilosis have increased recently. In our study, we aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy.

Systematic Review of Candidemia in Brazil: Unlocking Historical Trends and Challenges in Conducting Surveys in Middle-Income Countries.

INTRODUCTION: Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts. METHODS: We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia. RESULTS: Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered. CONCLUSION: Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.

An Alarming Rise of Candidemia Caused by Non-Albicans Candida Species in Intensive Care Unit in Mymensingh, Bangladesh.

In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.

The Light-activated Effect of Natural Anthraquinone Parietin against Candida auris and Other Fungal Priority Pathogens.

Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions (λ = 428 nm, H = 30 J/cm2, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for C. tropicalis and Cryptococcus neoformans, c = 0.313 mg/L (1.10 µM) for C. auris, c = 0.625 mg/L (2.20 µM) for C. glabrata, and c = 1.250 mg/L (4.40 µM) for C. albicans. Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all Candida species tested (including C. auris) and Cryptococcus neoformans, covering three of the four critical threats on the WHO's most recent fungal priority list.

Syzygium aromaticum essential oil and its major constituents: Assessment of activity against Candida spp. and toxicity.

Syzigium aromaticum essential oil (EO), eugenol, and ß-caryophyllene were evaluated regarding antifungal, antibiofilm, and in vitro toxicity. Additionally, in vivo toxicity of EO was observed. Anti-Candida activity was assessed through broth microdilution assay for all compounds. Time-kill assay (0, 1, 10, 30 min, 1, 2, and 4 h) was used to determine the influence of EO and eugenol on Candida Growth kinetics. Thereafter, both compounds were evaluated regarding their capacity to act on a biofilm formation and on mature biofilm, based on CFU/ml/g of dry weight. Cell Titer Blue Viability Assay was used for in vitro cytotoxicity, using oral epithelial cells (TR146) and human monocytes (THP-1). Lastly, Galleria mellonella model defined the EO in vivo acute toxicity. All compounds, except ß-cariofilene (MIC > 8000 µg/ml), presented antifungal activity against Candida strains (MIC 500-1000 µg/ml). The growth kinetics of Candida was affected by the EO (5xMIC 30 min onward; 10xMIC 10 min onward) and eugenol (5xMIC 10 min onward; 10xMIC 1 min onward). Fungal viability was also affected by 5xMIC and 10xMIC of both compounds during biofilm formation and upon mature biofilms. LD50 was defined for TR146 and THP1 cells at, respectively, 59.37 and 79.54 µg/ml for the EO and 55.35 and 84.16 µg/ml for eugenol. No sign of toxicity was seen in vivo up to 10mg/ml (20 x MIC) for the EO. S. aromaticum and eugenol presented antifungal and antibiofilm activity, with action on cell growth kinetics. In vivo acute toxicity showed a safe parameter for the EO up to 10 mg/ml.

Clinical and epidemiological aspects of Candida yeast infections and rational use of antifungals.

Aim: The objective of this study was to evaluate the clinical and epidemiological aspects of Candida infections. Methods: The study relied on the analysis of electronic medical records. Results: Among 183 patients with positive fungal infections, 57 were from the community and 126 from hospitals. Females predominated in both groups (82.4% in the community, 54.7% in hospitals). Non-albicans Candida spp. accounted for 62.8% of cases. Antifungal therapy was prescribed for 67 patients, with a 55.6% mortality rate. Conclusion: The increasing prevalence of non-albicans Candida species highlights the need for better candidiasis monitoring and control, especially concerning antifungal use amidst rising antimicrobial resistance, particularly in empirical therapy scenarios.

Fungal infections, particularly those caused by a group of yeasts called Candida, are a major concern. This study looks at clinical laboratory and medical records. We found that certain species of Candida not previously associated with human disease are common. We also noted the inappropriate use of antifungal medication, highlighting the need for healthcare workers to carefully diagnose patients and make appropriate decisions when treating fungal infections.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

BACKGROUND: Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. METHODS: A two-phase surveillance project was conducted in Beijing, China, involving 37 centres across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. FINDINGS: We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared with the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. CONCLUSIONS: Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

Paranazzamides A and B, new cyclic dipeptides containing a C7-prenylated tryptophan, produced by pathogenic reptile fungi Paranannizziopsis sp. UH-21.

Two new cyclic dipeptides, paranazzamides A (1) and B (2) containing a C7-prenylated tryptophan, were isolated from a culture broth of snake fungal disease-isolate Paranannizziopsis sp. UH-21. This is the first report on the new secondary metabolites from Paranannizziopsis sp. The planar structures of 1 and 2 were elucidated using various spectroscopic techniques including MS and 1D/2D NMR. The absolute configuration of 1 was assigned by comparison with the synthesized compound. Compounds 1 and 2 exhibited no antifungal activity, no antibacterial activity, and no cytotoxic activity even at a concentration of 128 µg ml-1, whereas 1 and 2 exhibited amphotericin B potentiating activity against Candida auris in combination treatment.

Understanding the mechanism of action of protease inhibitors in controlling the growth of the Candida Genus: potential candidates for development of new antifungal molecules.

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.

Lactoferrin as a potential therapeutic for the treatment of Candida-associated denture stomatitis.

BACKGROUND: The use of prostheses in the oral cavity creates favorable conditions for Candida colonization, which may subsequently lead to Candida-associated denture stomatitis (CADS). Due to its many contributing factors and frequent relapses, CADS is difficult to manage. Given the rise in drug resistance among fungal species, it is critical to develop new therapeutic approaches, reduce the required dosage of medications, and minimize the toxicity and side effects of therapy. HIGHLIGHT: Salivary lactoferrin, a multifunctional glycoprotein, is thought to be the first line of defense against microbial invasion of mucosal surfaces. CONCLUSION: Current research emphasizes the capability of lactoferrin and its derivatives to eliminate a broad spectrum of Candida species. It may be an appealing option for use in monotherapy or in combination with common medications for oral stomatitis treatment. This review provides an overview of the current understanding of lactoferrin's anti-fungal effects in oral candidiasis.

Treatment of vaginitis caused by non-albicans Candida species.

INTRODUCTION: In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections. AREAS COVERED: In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients. EXPERT OPINION: We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England.

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.

Phytolacca tetramera berries extracts and its main constituents as potentiators of antifungal drugs against Candida spp.

BACKGROUND: Extensive antifungal drug use has enhanced fungal resistance, resulting in persistent mycoses. Combining antifungal plant extracts/compounds with these drugs offers good alternatives to increase the activity of both partners, minimize side effects, and overcome drug resistance. In our previous study, Phytolacca tetramera berries extracts demonstrated activity against Candida spp., correlating with the amount of the main constituent phytolaccoside B and its genin, phytolaccagenin. The extracts and phytolaccagenin altered the fungal plasma membrane by binding to ergosterol, whereas phytolaccoside B increased chitin synthase activity. However, the presence of triterpenoid saponins in Phytolacca spp. has been linked to acute toxicity in humans. PURPOSE: This study aimed to evaluate combinations of P. tetramera berries extracts, phytolaccoside B and phytolaccagenin, together with commercial antifungals [amphotericin B, fluconazole, itraconazole, posaconazole, and caspofungin] against Candida albicans and Candida glabrata, to find synergistic effects with multi-target actions, in which the doses of both partners are reduced, and therefore their toxicity. Additionally, we intended to explore their anti-virulence capacity, thereby hindering the development of drug-resistant strains. METHODS: The effects of these combinations were evaluated using both the checkerboard and isobologram methods. Fractional Inhibitory Concentration Index and Dose Reduction Index were calculated to interpret the combination results. To confirm the multi-target effect, studies on mechanisms of action of synergistic mixtures were performed using ergosterol-binding and quantification assays. The ability to inhibit Candida virulence factors, including biofilm formation and eradication from inert surfaces, was also evaluated. Quantification of active markers was performed using a validated UHPLC-ESI-MS method. RESULTS: Eight synergistic combinations of P. tetramera extracts or phytolaccagenin (but not phytolaccoside B) with itraconazole or posaconazole were obtained against C. albicans, including a resistant strain. These mixtures acted by binding to ergosterol, decreasing its whole content, and inhibiting Candida biofilm formation in 96-well microplates and feeding tubes in vitro, but were unable to eradicate preformed biofilms. CONCLUSIONS: This study demonstrated the synergistic and anti-virulence effects of P. tetramera berries extracts and phytolaccagenin with antifungal drugs against Candida spp., providing novel treatment avenues for fungal infections with reduced doses of both natural products and commercial antifungals, thereby mitigating potential human toxicity concerns.

Candida auris from the Egyptian cobra: Role of snakes as potential reservoirs.

Candida auris represents one of the most urgent threats to public health, although its ecology remains largely unknown. Because amphibians and reptiles may present favorable conditions for C. auris colonization, cloacal and blood samples (n = 68), from several snake species, were cultured and molecularly screened for C. auris using molecular amplification of glycosylphosphatidylinositol protein-encoding genes and ribosomal internal transcribed spacer sequencing. Candida auris was isolated from the cloacal swab of one Egyptian cobra (Naja haje legionis) and molecularly identified in its cloaca and blood. The isolation of C. auris from wild animals is herein reported for the first time, thus suggesting the role that these animals could play as reservoirs of this emerging pathogen. The occurrence of C. auris in blood requires further investigation, although the presence of cationic antimicrobial peptides in the plasma of reptiles could play a role in reducing the vitality of the fungus.

Candida auris represents one of the most urgent threats to public health. In this study, we reported for the first time the isolation of C. auris from snake thus suggesting the role of these animals as reservoirs of this emerging pathogen.