Candida Auris Infection Research Articles

Mortality and Associated Risk Factors in Patients With Candida auris: Insights From a Tertiary Care Hospital in Bahrain.

Introduction Candida auris poses a significant healthcare challenge due to its high mortality rates, difficulties in identification, and resistance to antifungal treatment. This study aims to identify risk factors associated with 30-day mortality in patients with either invasive Candida auris infection or colonization. Methods We conducted a prospective study at Salmaniya Medical Complex, a tertiary care hospital in Bahrain, from September 2023 to February 2024. The study included 59 patients infected or colonized by Candida auris. Data were systematically collected from patient records, including demographics, clinical characteristics, and outcomes. Risk factors for 30-day mortality were analyzed using both univariate and multivariate statistical methods. Results Among the 59 patients studied, the mean age was 63.9 years, and the cohort was predominantly male (74.6%). Key findings include a high prevalence of multiple indwelling catheters (44.2%) and recent intubation (42.4%). Candida auris was most frequently isolated from the groin (33.9%) and urine (25.4%), with a notable presence in the axillary regions (23.7%). The mortality rate was 44.1%. Univariate and multivariate analyses revealed that age (≥65 years), multiple indwelling catheters, ICU admission for over 24 hours, and recent intubation were significant risk factors for mortality while chronic kidney disease did not retain its significance in the multivariate model. Conclusion The study underscores the critical need for focused infection control and strong antimicrobial stewardship to address the high mortality associated with Candida auris infections. Emphasizing the importance of early detection and a multidisciplinary approach, these strategies are essential for managing and mitigating the impact of Candida auris in healthcare settings.

Analogues 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 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.

Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris

Introduction: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). Interpretation: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodeling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

Candida auris Screening of High-Risk Patients: A Descriptive Comparison of 2 Strategies.

Background: Candida auris infection is associated with high morbidity and mortality. C. auris can persist in the healthcare environment and is associated with outbreaks. We compare screening strategies for C. auris in two high-risk patient populations. Methods: Our center is a tertiary, 865-bed hospital. In the context of known regional outbreaks of C. auris in post-acute care (PAC) facilities, we experienced extended clusters of apparent C. auris acquisition across several hospital units. Hospital acquisition was defined as new C. auris in clinical cultures in patients with no known history of C. auris colonization/infection. We performed point prevalence surveys (PPS) on affected units weekly until all tests were negative for two consecutive weeks. We also initiated admission screening for C. auris for patients admitted from PAC. All screening swabs were collected per CDC’s procedure. Tests were performed either by RT-PCR or Chromagar C. auris media, depending on availability. We compared the overall positivity rates of exposure PPS versus PAC admission screenings using Z-test for two proportions with statistical significance set at p < 0 .05 Results: From 2/2023-12/2023, a total of 533 tests on 367 unique patients were processed during PPS; 512 tests were negative and 21 were positive (3.9% positivity rate). Three additional samples were either unable to be processed or indeterminate. There were 68 patients who had repeat testing weekly for ≥2 weeks. Most remained negative, but 5 tested positive after variable amounts of negative-week intervals: 3 patients at week 2, 1 patient at week 4 and 1 patient at week 5. From 8/2023 to 12/2023, a total of 89 patients admitted from 35 different PAC facilities underwent admission screening for C. auris. Only three patients were positive (3.4%), each from a different facility. The difference in the positivity rates between PPS and PAC was not statistically significant (Z-score 0.25, p = 0.79). Discussion: Our C. auris screening strategies found similar positivity rates for patients admitted to the hospital from PACs compared to targeted PPS in the setting of apparent hospital acquisition events. These strategies may be considered as complementary. Facilities experiencing apparent acquisition events should consider screening high-risk admissions to identify and isolate colonized patients, particularly if standard infection prevention practices are being performed with high fidelity.

A simple and sensitive test for Candida auris colonization, surveillance, and infection control suitable for near patient use.

This study has the potential to offer a better solution to healthcare providers at hospitals and long-term care facilities in their ongoing efforts for effective and timely control of Candida auris infection and hence quicker response for any potential future outbreaks.

Fluphenazine is Effective Against Candida auris Infection

Fluphenazine is Effective Against Candida auris Infection

Spectrum of infection and outcomes in individuals with Candida auris infection in Qatar.

We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar. We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality. Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17). Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD.

Effect of Conformational Variability on the Drug Resistance of Candida auris ERG11p and FKS1.

Candida auris infection has been recognized as an urgent threat to antifungal drug resistance, and the Eagle effect of C. auris FKS1 (1,3-β-d-glucan synthase) wild-type isolates has also been noted. The Eagle effect, namely, where higher concentrations of antifungals reduce fungicidal activity relative to lower concentrations, is a confounding factor of apparent antifungal resistance, but the detailed mechanism remains unclear. Here, we present the conformational variability of mutation sites for ERG11p (lanosterol 14α-demethylase) and FKS1 from deep neural network-based prediction along with the reported X-ray crystallographic and cryo-electron microscopy (cryo-EM) structures of antifungals. The sequence variability maps provide valuable insights into the inconsistent correlation between azole resistance and the mysterious Eagle effect with the dispersion of minimal inhibitory concentration (MIC) for echinocandin resistance. The conformational variability prediction supports the hypothesis that mutations K143R of clade I, VF125AL of clade III, and Y132F of clade IV for C. auris ERG11p make the corresponding site variable and that an increased population of invisible variable conformations potentially contributes to triazole resistance. In contrast, the predicted rigid conformation by the S639F mutation of hot spot region 1 (HS1) for FKS1 suggests that caspofungin (CAS) is involved in an uncompetitive inhibition, and a decreased population of the CAS-bound state of FKS1 with Rho1 leads to drug resistance. The predicted variable HS1 region for FKS1 WT isolates and the rigid one for FKS1 S639F mutants support the in vivo drug response and the in vitro MIC dispersion. A plausible mechanism of the Eagle effect is hereby proposed, namely, that a high concentration of CAS with a high membrane affinity reduces the population of the CAS-bound state of FKS1 with Rho1, as well as accompanying events such as aggregation or association depending on the conformational variability of HS1.

Clinical characteristics and risk factors for mortality in Candida auris infections

AbstractBackgroundCandida auris infections pose a threat to public health, necessitating increased awareness in China. This study aimed to analyze the strains of C. auris, assess the infection status, and investigate clinical characteristics and risk factors for mortality.MethodsA retrospective analysis was conducted on 18 patients with Candida auris infection. We focused on evaluating basic characteristics, strain sources, and antibacterial susceptibility test results. Statistical methods were used to determine clinical features and identify risk factors for death.ResultsThe strain type, composition ratio, and specimen source of C. auris were not associated with mortality. Neither the infection index nor the length of hospitalization showed an association with the prognosis. However, significant risk factors for mortality included cerebral infarction, cardiac disease, renal dysfunction, hypoproteinemia, and anemia (all p &lt; 0.05).ConclusionsCerebral infarction, cardiac disease, renal dysfunction, hypoproteinemia, and anemia are significant risk factors for death in C. auris infections. These findings indicate the importance of recognizing and addressing these factors in the clinical management of C. auris infection.

Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris Infection in a Mice Model.

The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.

Candida auris Infection, a Rapidly Emerging Threat in the Neonatal Intensive Care Units: A Systematic Review.

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.

The First Report of Candida Auris Infection in Vietnam.

Further research on Candida auris infections is warranted, focusing on newly observed clinical features present in all cases in this report, including hypoalbuminaemia and corticosteroid use during hospitalisation.While Candida auris remains susceptible to commonly used antifungal drugs, one case of resistance to amphotericin B has been documented, possibly due to prior exposure to this antifungal agent.

Pathobiology of Candida auris infection analyzed by multiplexed imaging and single cell analysis.

Fungal organisms contribute to significant human morbidity and mortality and Candida auris (C. auris) infections are of utmost concern due to multi-drug resistant strains and persistence in critical care and hospital settings. Pathogenesis and pathology of C. auris is still poorly understood and in this study, we demonstrate how the use of multiplex immunofluorescent imaging (MxIF) and single-cell analysis can contribute to a deeper understanding of fungal infections within organs. We used two different neutrophil depletion murine models (treated with either 1A8-an anti-Ly6G antibody, or RB6-8C5-an anti-Ly6G/Ly6C antibody; both 1A8 and RB6-8C5 antibodies have been shown to deplete neutrophils) and compared to wildtype, non-neutropenic mice. Following pathologist assessment, fixed samples underwent MxIF imaging using a C. albicans antibody (shown to be cross-reactive to C. auris) and immune cell biomarkers-CD3 (T cells), CD68 (macrophages), B220 (B cells), CD45 (monocytes), and Ly6G (neutrophils) to quantify organ specific immune niches. MxIF analysis highlighted the heterogenous distribution of C. auris infection within heart, kidney, and brain 7 days post-infection. Size and number of fungal abscesses was greatest in the heart and lowest in brain. Infected mice had an increased count of CD3+, CD68+, B220+, and CD45+ immune cells, concentrated around C. auris abscesses. CD68+ cells were predominant in wildtype (non-neutropenic mice) and CD3+/CD45+ cells were predominant in neutropenic mice, with B cells being the least abundant. These findings suggest a Th2 driven immune response in neutropenic C. auris infection mice models. This study demonstrates the value of MxIF to broaden understanding of C. auris pathobiology, and mechanistic understanding of fungal infections.

Characteristics and Mitigation Measures of Candidaauris Infection: Descriptive Analysis from a Quaternary Care Hospital in Saudi Arabia, 2021–2022

ObjectiveTo analyze the characteristics of C. auris cases, and to describe the interventions applied for improving the diagnosis and controlling the transmission.MethodMedical records of C. auris cases reported between January 2021 until June 2022 at King Saud Medical City (KSMC), Riyadh, Kingdom of Saudi Arabia have been reviewed. We analyzed the demographic and clinical characteristics of the cases to illustrate the possible contributing factors with C. auris infection. A multidisciplinary committee has been formulated to investigate the potential source of the outbreak among clusters of cases in the intensive care units (ICU). A bundle of mitigation measures has been applied which was successful to contain the outbreak.ResultsDuring the study period, a total of 129 cases of C. auris were identified, their mean age is 47 ± 22.3 SD, and 72.1% are males. 57% of cases were colonized, all of them were identified through active screening. A number of comorbidities were present including 27.9% were having hypertension, 27.1% with diabetes, 22.5% with COVID-19 and 20.2% with respiratory diseases. The average length of stay before reported positive was 36.23 days. 78.3% of those patients were in the critical care unit, 73.6% with vascular catheter, 88% with urinary catheters and 66.7% with mechanical ventilation. The vast majority of patients were using multiple antibiotics (86%). As per the univariate logistic model, risk factors significantly associated with mortality were (Age, Trauma RTA, ICU, Vascular Access, Foley Catheters, Mechanical Ventilation, Tracheostomy and Endotracheal Tubes) with p values (0.0038, 0.0159, 0.0108, 0.0122, 0.0071, <.0001, 0.0148 and 0.0107), respectively. Multivariate logistic regression showed that having a Foley Catheter was the only statistically significant factor associated with mortality.ConclusionThis retrospective analysis highlights the main characteristics associated with C. auris-infected patients. In addition, it highlights the effectiveness of the bundle of mitigation strategies applied to limit the spread of C. auris in healthcare facilities.

The Impact of COVID-19 on the Epidemiology and Outcomes of Candidemia: A Retrospective Study from a Tertiary Care Center in Lebanon.

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19-associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4%, respectively). The mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported candidemia mortality rate observed in studies involving ICU patients. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs. 78.1%; p = 0.76). Performing ophthalmic examination (p = 0.002), CVC removal during the 48 h following the candidemia (p = 0.008) and speciation (p = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species such as C. auris.

Emergence of Candida auris infection: A review

Emergence of Candida auris infection: A review

Discovery of a new chemical scaffold for the treatment of superbug Candida auris infections

ABSTRACT Candida auris has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound A1 showed potent in vitro and in vivo efficacy against Candida auris infection. Mechanism investigation revealed that compound A1 blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound A1 represents a promising lead compound to combat drug-resistant candidiasis.

The Emergence and Persistence of Candida auris in Western New York With No Epidemiologic Links: A Failure of Stewardship?

Reports of Candida auris infection in patients without epidemiologic links to prior outbreaks are scarce. We describe the genomic epidemiology of such a case in Western New York. Before emergence, the patient received >60 days of excess antibiotics. Candida auris was recovered on near-patient surfaces after enhanced terminal cleanings.

Synthesis of oligosaccharides to identify an immunologically active epitope against Candida auris infection.

Candida auris (C. auris) is an emerging multidrug-resistant fungal pathogen that represents a significant public health challenge as it can spread rapidly and result in high mortality rates. The mannans on the C. auris cell surface are potent immunogens and attractive targets for developing a glycoconjugate vaccine. We synthesized the oligosaccharides resembling cell surface mannans of C. auris and printed them onto microarray slides that were used to screen plasma from mice infected with C. auris. IgM antibodies in mouse plasma recognize the β-1,2 linkage present in C. auris surface mannans. Disaccharide 19 emerged from glycan array screening as a lead for developing a vaccine against C. auris, as the majority of patient plasma samples showed antibodies against this glycan. The synthetic oligosaccharides can be used for the early detection of C. auris infections.

First Candida auris Infection Case from İzmir: Polymicrobial Diabetic Foot Infection Resulting in Amputation

First Candida auris Infection Case from İzmir: Polymicrobial Diabetic Foot Infection Resulting in Amputation