Alkaloids solenopsins from fire ants display in vitro and in vivo activity against the yeast Candida auris.

The urgency surrounding Candida auris as a public health threat is highlighted by both the Center for Disease Control (CDC) and World Health Organization (WHO) that categorized this species as a priority fungal pathogen. Given the current limitations of antifungal therapy for C. auris, particularly due to its multiple resistance to the current antifungals, the identification of new drugs is of paramount importance. Some alkaloids abundant in the venom of the red invasive fire ant (Solenopsis invicta), known as solenopsins, have garnered attention as potent inhibitors of bacterial biofilms, and there are no studies demonstrating such effects against fungal pathogens. Thus, we herein investigated the antibiotic efficacy of solenopsin alkaloids against C. auris biofilms and planktonic cells. Both natural and synthetic solenopsins inhibited the growth of C. auris strains from different clades, including fluconazole and amphotericin B-resistant isolates. Such alkaloids also inhibited matrix deposition and altered cellular metabolic activity of C. auris in biofilm conditions. Mechanistically, the alkaloids compromised membrane integrity as measured by propidium iodide uptake in exposed planktonic cells. Additionally, combining the alkaloids with AMB yielded an additive antifungal effect, even against AMB-resistant strains. Finally, both extracted solenopsins and the synthetic analogues demonstrated protective effect in vivo against C. auris infection in the invertebrate model Galleria mellonella. These findings underscore the potent antifungal activities of solenopsins against C. auris and suggest their inclusion in future drug development. Furthermore, exploring derivatives of solenopsins could reveal novel compounds with therapeutic promise.

Analogs of the anti-malaria drug mefloquine have broad-spectrum antifungal activity and are efficacious in a model of disseminated Candida auris infection.

Only three classes of antifungal drugs are currently in clinical use. Here, we report that derivatives of the malarial drug mefloquine have broad-spectrum antifungal activity including difficult-to-treat molds and endemic fungi. Pharmacokinetic and efficacy studies of NSC-4377 indicate that it penetrates the central nervous system and is active against Candida auris in vivo. These data strongly support the further development of mefloquine analogs as a potentially new class of antifungal molecules.

Absence of measurable quantities of Candida auris and Cryptococcus spp. in the gut microbiota of Ghanaian individuals with and without HIV infection as confirmed by applying multiple real-time PCR assays.

Introduction. Fungal infections are relevant health risks for individuals with acquired immunodeficiency in the resource-limited tropics, but available surveillance data are scarce. For Candida auris and Cryptococcus spp., the evolution from environmental reservoirs to human pathogens causing life-threatening diseases is currently discussed as a public health concern in the context of climate change and limited treatment options.Gap statement. Uncovering the gastrointestinal tract as an epidemiological niche of fungi emerging from the environment into individuals for whom fungal infections are not diagnosed.Aim. To contribute to data on the local epidemiology of C. auris and Cryptococcus spp. in Western African Ghana by analysing gastrointestinal samples of Ghanaian individuals.Methodology. Four real-time PCR assays targeting C. auris and five real-time PCR assays targeting Cryptococcus spp. were applied with stool samples of 875 non-age-stratified Ghanaian HIV patients and 30 Ghanaian control individuals without known HIV infection. Also, 664 samples from Ghanaian children under 2 years of age were investigated. The true abundance of the target micro-organism was considered as unlikely in the case of one or fewer positive signals, likely in the case of two to three positive signals and highly likely in the case of four or more positive signals per sample in the real-time PCR assays.Results. The combined application of sensitive, target-specific real-time PCR assays indicates that neither C. auris, Cryptococcus neoformans complex nor Cryptococcus gattii complex were part of the gut microbiota of Ghanaian individuals with or without HIV infection.Conclusion. Despite the significant disease burden from these pathogens in immunosuppressed Ghanaian individuals, detection from gastrointestinal samples was unlikely, which should be taken into account when discussing screening strategies for these fungi of public health concern. In contrast, the detection of these fungi from such samples should not routinely be considered as commensal colonization flora.

Recent increase in Candida auris frequency in the SENTRY surveillance program: antifungal activity and genotypic characterization.

We observed an increase in the frequency of Candida auris among invasive candidiasis isolates in the 2022 SENTRY Antifungal Surveillance Program compared to prior years: ≤0.1% before 2018, 0.4%-0.6% from 2018 to 2021, and 1.6% in 2022. C. auris isolates were collected in seven countries, but 28 (35.9%) isolates were recovered in the USA (five states; more common in New York, Texas, and New Jersey) and 26 (33.3%) in Panama. Greece and Turkey had 12 and 9 isolates, respectively. Overall, 82.1% of the isolates were resistant to fluconazole; 17.9% were resistant to amphotericin B; and 1.3% were resistant to caspofungin, anidulafungin, or micafungin (Centers for Disease Control and Prevention tentative resistance breakpoints). Rezafungin inhibited 96.2% of the isolates (Clinical and Laboratory Standards Institute susceptibility breakpoint). Pandrug resistance was not observed, but 17.9% of the isolates were resistant to fluconazole and amphotericin B. South Asian (Clade I) isolates were most common (n = 40, 51.3%); of these, 97.5% were resistant to fluconazole and 30.0% were resistant to amphotericin B. Thirty (38.5%) isolates belonged to the South American region (Clade IV), and 56.7% of those were resistant to fluconazole and 6.7% to amphotericin B. Seven isolates belonged to the South African Clade III and one to East Asian Clade II. Erg11 (Y132F, K143R, and F126L) and MRR1 (N647T) alterations were detected. One isolate that was resistant to all echinocandins carried an FKS R1354G alteration. Two isolates displayed elevated rezafungin minimum inhibitory concentration (MIC) values but low MIC values against other echinocandins and no FKS alterations. As C. auris is spreading globally, monitoring this species is prudent.

Amphotericin B and micafungin duo-loaded nanoemulsion as a potential strategy against Candida auris biofilms.

Candida auris is a multidrug-resistant yeast that has seen a worrying increase during the COVID-19 pandemic. Give7/n this, new therapeutic options, such as controlled-release nanomaterials, may be promising in combating the infection. Therefore, this study aimed to develop amphotericin B (AmB) and micafungin (MICA)-loaded nanoemulsions (NEMA) and evaluated against biofilms of C. auris. Nanoemulsions (NEs) were characterized and determined minimum inhibitory concentration MIC90, checkerboard and anti-biofilm. NEMA presented a size of 53.7 and 81.4 nm for DLS and NTA, respectively, with good stability and spherical morphology. MICAmB incorporated efficiency was 88.4 and 99.3%, respectively. The release results show that AmB and MICA obtained a release of 100 and 63.4%, respectively. MICAmB and NEMA showed MIC90 values of 0.015 and 0.031 ug/mL, respectively and synergism. NEMA showed greater metabolic inhibition and morphological changes in mature biofilms. This drugs combination and co-encapsulation proved to be a promising therapy against C. auris biofilms.

Early Introductions of Candida auris Detected by Wastewater Surveillance, Utah, USA, 2022-2023.

Candida auris is considered a nosocomial pathogen of high concern and is currently spreading across the United States. Infection control measures for C. auris focus mainly on healthcare facilities, yet transmission levels may already be significant in the community before outbreaks are detected in healthcare settings. Wastewater-based epidemiology (culture, quantitative PCR, and whole-genome sequencing) can potentially gauge pathogen transmission in the general population and lead to early detection of C. auris before it is detected in clinical cases. To learn more about the sensitivity and limitations of wastewater-based surveillance, we used wastewater-based methods to detect C. auris in a southern Utah jurisdiction with no known clinical cases before and after the documented transfer of colonized patients from bordering Nevada. Our study illustrates the potential of wastewater-based surveillance for being sufficiently sensitive to detect C. auris transmission during the early stages of introduction into a community.

Evaluation of an automated far ultraviolet-C light technology for decontamination of surfaces and aerosolized viruses in bathrooms.

BACKGROUND: Aerosols generated during toilet flushing are a potential source for transmission of viral and bacterial pathogens in bathrooms. However, manual decontamination of bathrooms after each use is not feasible. METHODS: We tested the efficacy of a wall-mounted far ultraviolet-C (UV-C) light technology that only delivers far UV-C when people are not present for decontamination of surfaces and aerosolized viral particles in an unoccupied hospital bathroom. A quantitative disk carrier test method was used to test efficacy against organisms on steel disk carriers placed in 9 sites in the bathroom with an exposure time of 45 min and 2 h; Clostridioides difficile spores were also exposed for 24 h. Efficacy against aerosolized bacteriophage MS2 was tested with a 45-minute exposure. RESULTS: The far UV-C technology reduced methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Candida auris, and bacteriophage MS2 on steel disk carriers by ≥ 1.2 log10 (range, 1.2 to 4.2 log10) at all test sites after 2 h of exposure. The technology reduced C. difficile spores by < 1 log10 after 2 h exposure, but 4 of 9 test locations had ≥ 2 log10 reductions after 24 h exposure. Aerosolized bacteriophage MS2 was reduced by 4 log10 plaque-forming units in 45 min. CONCLUSIONS: The far UV-C light technology could potentially be useful for automated decontamination of air and surfaces in bathrooms in healthcare and community settings.

Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris.

Candida auris has emerged as a significant healthcare-associated pathogen due to its multidrug-resistant nature. Ongoing constraints in the discovery and provision of new antifungals create an urgent imperative to design effective remedies to this pressing global blight. Herein, we screened a chemical library and identified aryl-carbohydrazide analogs with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 [N'-(2,6-dichlorophenyl)-5-nitro-furan-2-carbohydrazide] exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a Δ(9) fatty acid desaturase, is the likely target of SPB00525. An analog of the latter, HTS06170 [N'-(2,6-dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide], had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate the survival of Galleria mellonella larvae used as systemic candidiasis model. These data suggest that inhibiting fungal Δ(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.

Baicalein induces apoptosis by targeting ribosomes in Candida auris.

The emergence of the "super fungus" Candida auris poses a significant threat to human health, given its multidrug resistance and high mortality rates. Therefore, developing a new antifungal strategy is necessary. Our previous research showed that Baicalein (BE), a key bioactive compound from the dried root of the perennial herb Scutellaria baicalensis Georgi, has strong fungistatic properties against C. auris. Nevertheless, the antifungal activity of BE against C. auris and its mechanism of action requires further investigation. In this study, we explored how BE affects this fungus using various techniques, including scanning electron microscopy (SEM), Annexin V-FITC apoptosis detection, CaspACE FITC-VAD-FMK In Situ Marker, reactive oxygen species (ROS) assay, singlet oxygen sensor green (SOSG) fluorescent probe, enhanced mitochondrial membrane potential (MMP) assay with JC-1, DAPI staining, TUNEL assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our findings revealed that BE induced several apoptotic features, including phosphatidylserine (PS) externalization, metacaspase activation, nuclear condensation and DNA fragmentation. BE also increased intracellular ROS levels and altered mitochondrial functions. Additionally, transcriptomic analysis and RT-qPCR validation indicated that BE may induce apoptosis in C. auris by affecting ribosome-related pathways, suggesting that ribosomes could be new targets for antifungal agents, in addition to cell walls, membranes, and DNA. This study emphasizes the antifungal activity and mechanism of BE against C. auris, offering a promising treatment strategy for C. auris infection.

In Vivo Efficacy of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in a Neutropenic Mouse Bloodstream Infection Model.

OBJECTIVES: Rezafungin is the first new drug approved to treat candidaemia and invasive candidiasis in more than 10 years. However, data are scant on the in vivo efficacy of rezafungin and the other three approved echinocandins against different Candida auris clades. METHODS: This study involved 10 isolates representing 4 C. auris clades: South Asian (n = 2), East Asian (n = 2), South African (n = 2), and South American (n = 4, including 2 environmental isolates). In the lethality experiment and fungal tissue burden experiment (kidney, heart, and brain), cyclophosphamide-treated BALB/c male mice were intravenously infected (107 and 8 × 106 colony-forming units [CFU]/mouse, respectively). A 20 mg/kg dose of rezafungin was administered on days 1, 3, and 6. Alternatively, beginning 24 h post-infection, mice received 3 mg/kg of caspofungin, 5 mg/kg of micafungin, or 5 mg/kg of anidulafungin once daily for 6 days. RESULTS: Regardless of isolate and clade, all echinocandin regimens improved survival after 21 days (p = 0.0041 to p < 0.0001). All echinocandins frequently produced >3-log mean CFU/g decreases in the fungal kidney and heart burdens, although some of these decreases were not statistically significant. Rezafungin, regardless of clade, produced 3-5 and 2-4 log CFU/g decreases in the kidney and heart burdens, respectively. Echinocandins did not inhibit fungal growth in the brain. Histopathological examination performed on day 7 showed no fungal cells in the heart and kidneys of rezafungin-treated mice and to a lesser extent, caspofungin-treated mice, regardless of the clinical isolate. All echinocandin-treated mice showed medium and/or large foci of fungal cells in their cerebrum or cerebellum. CONCLUSIONS: Regardless of the C. auris clade, rezafungin activity in vivo was comparable to or improved over that of the three previously approved echinocandins.

Evaluation of Etest and MICRONAUT-AM Assay for Antifungal Susceptibility Testing of Candida auris: Underestimation of Fluconazole Resistance by MICRONAUT-AM and Overestimation of Amphotericin B Resistance by Etest.

Multidrug-resistant Candida auris has recently caused major outbreaks in healthcare facilities. Rapid and accurate antifungal susceptibility testing (AST) of C. auris is crucial for proper management of invasive infections. The Commercial Sensititre Yeast One and Vitek 2 methods underestimate or overestimate the resistance of C. auris to fluconazole and amphotericin B (AMB). This study evaluated the AST results of C. auris against fluconazole and AMB by gradient-MIC-strip (Etest) and broth microdilution-based MICRONAUT-AM-EUCAST (MCN-AM) assays. Clinical C. auris isolates (n = 121) identified by phenotypic and molecular methods were tested. Essential agreement (EA, ±1 two-fold dilution) between the two methods and categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints were determined. Fluconazole resistance-associated mutations were detected by PCR-sequencing of ERG11. All isolates identified as C. auris belonged to South Asian clade I and contained the ERG11 Y132F or K143R mutation. The Etest-MCN-AM EA was poor (33%) for fluconazole and moderate (76%) for AMB. The CA for fluconazole was higher (94.2%, 7 discrepancies) than for AMB (91.7%, 10 discrepancies). Discrepancies were reduced when an MCN-AM upper-limit value of 4 µg/mL for fluconazole-susceptible C. auris and an Etest upper-limit value of 8 µg/mL for the wild type for AMB were used. Our data show that resistance to fluconazole was underestimated by MCN-AM, while resistance to AMB was overestimated by Etest when using the CDC's tentative resistance breakpoints of ≥32 µg/mL for fluconazole and ≥2 µg/mL for AMB. Method-specific resistance breakpoints should be devised for accurate AST of clinical C. auris isolates for proper patient management.

Assessment of LAMPAuris for Rapid Detection of Candida auris in Clinical Specimens.

Candida auris is a pathogenic yeast frequently exhibiting multidrug resistance and thus warrants special attention. The prompt detection and proper identification of this organism are needed to prevent its spread in healthcare facilities. The authors of this paper had previously developed LAMPAuris, a loop-mediated isothermal amplification assay, for the specific detection of C. auris. LAMPAuris is evaluated in this report for its ability to identify C. auris from five clades and to detect it from clinical specimens. A total of 103 skin swab samples were tested in comparison with a culture-based method and C. auris-specific SYBR green qPCR. The results show that the LAMPAuris assay had specificities ranging from 97 to 100% and sensitivities ranging from 66 to 86%. The lower sensitivity could be attributed to DNA degradation caused by the prolonged storage of the samples. In conclusion, LAMPAuris proved to be a rapid and reliable method for identifying C. auris and for detecting it in clinical specimens. Fresh specimens should ensure better yield and higher sensitivities.

Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.

INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.

Complete genome assembly of Candida auris representative strains of three geographical clades.

The complete genome assembly of Candida auris strains B11103, B11221, and B11244 is reported in this manuscript. These strains represent the three geographical clades, namely, South Asian (Clade I), South African (Clade III), and South American (Clade IV).

Fungal photoinactivation doses for UV radiation and visible light-a data collection.

Nearly two million people die each year from fungal infections. Additionally, fungal crop infections jeopardize the global food supply. The use of 254 nm UVC radiation from mercury vapor lamps is a disinfection technique known to be effective against all microorganisms, and there are surveys of published UVC sensitivities. However, these mainly focus on bacteria and viruses. Therefore, a corresponding overview for fungi will be provided here, including far-UVC, UVB, UVA, and visible light, in addition to the conventional 254 nm UVC inactivation. The available literature was searched for photoinactivation data for fungi in the above-mentioned spectral ranges. To standardize the presentation, the mean log-reduction doses were retrieved and sorted by fungal species, spectral range, wavelength, and medium, among others. Additionally, the median log-reduction dose was determined for fungi in transparent liquid media. Approximately 400 evaluable individual data sets from publications over the last 100 years were compiled. Most studies were performed with 254 nm radiation from mercury vapor lamps on Aspergillus niger, Candida albicans, and Saccharomyces cerevisiae. However, the data found were highly scattered, which could be due to the experimental conditions. Even though the number of individual data sets seems large, many important fungi have not been extensively studied so far. For example, UV irradiation data does not yet exist for half of the fungal species classified as "high priority" or "medium priority" by the World Health Organization (WHO). In addition, researchers should measure the transmission of their fungal suspensions at the irradiation wavelength to avoid the undesirable effects of either absorption or scattering on irradiation results.

Antibiofilm activity of truncated Staphylococcus aureus phenol soluble modulin α2 (SaΔ1Δ2PSMα2) against Candida auris in vitro and in an animal model of catheter-associated infection.

Candida auris has emerged as a major multidrug-resistant nosocomial pathogen. The organism exhibits a persistent colonising phenotype, and causes recalcitrant infections often strongly linked to biofilm formation. Alternate strategies are urgently needed to combat this yeast and its biofilm-associated phenotype. This work aimed to evaluate the efficacy of select staphylococcal phenol soluble modulins (PSMs), namely, a truncated version of Staphylococcus aureus PSMα2 shortened by two amino acids at the N-terminal (SaΔ1Δ2PSMα2) and Staphylococcus epidermidis PSMδ against C. auris in vitro and in vivo. The antifungal and antibiofilm activity was tested by broth microdilution and XTT dye reduction assay. Combination effect with antifungal drugs was determined by fractional inhibitory concentration test. The efficacy of combination therapy using SaΔ1Δ2PSMα2 with amphotericin B or caspofungin was evaluated in murine model of C. auris catheter-associated infection. Based on antifungal activity, antibiofilm activity and cytotoxicity data, SaΔ1Δ2PSMα2 exhibited promising activity against C. auris biofilms. Nearly 50 % inhibition in biofilm formation was noted with 0.5-2 µM of the peptide against multiple clinical and C. auris colonizing isolates. It was synergistic with amphotericin B (ΣFIC = 0.281) and caspofungin (ΣFIC = 0.047) in vitro, and improved the activity of voriconazole in voriconazole-resistant C. auris. Combination therapy using amphotericin B or caspofungin (1 µg/ml) with SaΔ1Δ2PSMα2 resulted in 99.5 % reduction in C. auris biofilm in murine model, even when the peptide was used at a concentration that was neither fungicidal nor antibiofilm (0.125 µM; ≈0.26 µg/ml). The study provides insight into the potential utility of SaΔ1Δ2PSMα2-antifungal drug combination against C. auris biofilm-associated infections.

Identifying Candida auris transmission in a hospital outbreak investigation using whole-genome sequencing and SNP phylogenetic analysis.

Candida auris poses a global public health challenge, causing multiple outbreaks within healthcare facilities. Despite advancements in strain typing for various infectious diseases, a consensus on the genetic relatedness threshold for identifying C. auris transmission in local hospital outbreaks remains elusive. We investigated genetic variations within our local isolate collection using whole-genome-based single nucleotide polymorphism (SNP) phylogenetic analysis. A total of 74 C. auris isolates were subjected to whole-genome sequencing (WGS) and SNP phylogenetic analysis via the QIAGEN CLC Genomics Workbench. Isolates included known related strains from the same patient, strains from different hospitals, strains from our hospital patients with no epidemiological link, and 19 patient isolates from a recent C. auris outbreak. All but three isolates were identified to be Clade IV. By examining the genetic diversities of C. auris within patients and between patients, we identified a SNP variation range of 0-13 for identifying related isolates. During an outbreak investigation, utilizing this range, maximum likelihood phylogenetic analysis revealed two distinct clusters that aligned with the epidemiological links. Determining a SNP variation range to delineate genetic relatedness among isolates is crucial for the application of WGS and SNP phylogenetic analysis in identifying C. auris transmission during hospital outbreak investigations. The use of WGS SNP phylogenetic analysis via the CLC Genomics Workbench has emerged as a valuable method for typing C. auris in clinical microbiology laboratories.

Genetic microevolution of clinical Candida auris with reduced Amphotericin B sensitivity in China.

The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the "super fungus", C. auris.

Candida auris: A focused review for emergency clinicians.

INTRODUCTION: Candida auris is an emerging pathogen and human health threat. However, diagnosis and treatment of fungal infection due to C. auris are challenging. OBJECTIVE: This narrative review provides a focused overview of C. auris for the emergency clinician. DISCUSSION: C. auris was first identified in 2009 and is currently present on all continents except Antarctica. C. auris possesses multiple genetic factors resulting in antimicrobial resistance, increased virulence and survival within the host, and environmental adaptation. It is readily transmitted from person to person and from the environment to a person, resulting in colonization. Infection may develop days to months following colonization, most commonly in those with immunocompromised state, significant comorbidities or other underlying conditions, healthcare exposure, and recent antimicrobial therapy. Candidemia, device infection (e.g., central venous catheter), soft tissue or wound infection, burn infection, osteomyelitis, myocarditis, meningitis, and urinary tract infection have been associated with C. auris. Samples should be obtained from the suspected site of infection for microbiological culture. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with reference databases to differentiate C. auris from other species is optimal for diagnosis, though other molecular testing methods are available. Treatment is challenging due to antifungal resistance, with over 90% resistant to fluconazole. Echinocandins are most commonly used as the first line therapy. Prevention of colonization and infection are vital and include screening in high-risk populations and strict adherence to infection prevention practices with contact precautions and hand hygiene, as well as appropriate decontamination of patient areas. CONCLUSION: An understanding of C. auris can assist emergency clinicians in the care of infected or colonized patients.

Candida auris: Understanding the dynamics of C. auris infection versus colonization.

Candida auris is a pathogen of growing public health concern worldwide. However, risk factors contributing to C. auris infection in patients colonized with C. auris remain unclear. Understanding these risk factors is crucial to prevent colonization-to-infection transition and devise effective preventive strategies. This study aimed to investigate risk factors associated with C. auris infection compared to colonization. The study included 97 patients who acquired laboratory-confirmed C. auris in either matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry or VITEK 2 system from October 2019 to June 2023. Baseline demographics and known risk factors associated with C. auris infection were collected from electronic medical records. The infection group had C. auris from a sterile site or non-sterile site with evidence of infection. The colonization group was followed up for a median of 30 days for any signs of infection. Associations between relevant variables and C. auris infection were assessed using multivariable logistic regression. The infection group (n = 31) was more likely to be bedbound, with longer hospital stays and more arterial catheters. Chronic kidney disease (odds ratio [OR] 45.070), carriage of multidrug-resistant organisms (OR 64.612), and vasopressor use for > 20 days (OR 68.994) were associated with C. auris infection, after adjusting for sex, age, and prior colonization with C. auris. Chronic kidney disease, carriage of multidrug-resistant organisms, and prolonged vasopressor use emerged as significant risk factors for C. auris infection compared to colonization. They could be used to predict C. auris infection early in patients colonized with C. auris.

Identifying risk factors for Candida auris infection should be an essential component of care in patients colonized with C. auris. Chronic kidney disease, carriage of multidrug-resistant organisms, and prolonged vasopressor use emerged as significant risk factors for C. auris infection.