Auris Candidemia Research Articles

Prevalence and Outcomes of Candida auris Infections in a Tertiary Hospital in the United Arab Emirates (UAE).

Background Candida auris (C. auris) is an emerging serious threat to healthcare settings, with an average mortality of 45% in cases of bloodstream infections. This study aimed to determine the prevalence of C. auris in a single center in the UAEduring the year 2022 and understand risk factors related to poor outcomes. Methods This retrospective cohort chart review at Al-Qassimi Hospital encompassed all confirmed Candida infections, including C. auris, from January to December 2022. The study involved male and female patients aged 13 years and older, using comprehensive data extracted from the hospital's electronic healthcare records. The analysis included clinical, laboratory, and epidemiological data. Adhering to the 2011 Declaration of Helsinki and Good Pharmacoepidemiology Practices, the study received Institutional Review Board approval, with informed consent waived due to its retrospective design. Data were summarized using appropriate statistical methods, including the unpaired t-test, Mann-Whitney U test, Chi-square test, and Fisher exact test. A significance level of 95% (p<0.05) was maintained throughout the statistical analyses. Results Of the 75 confirmed Candidainfections, 53 (70.7%) were C. auris-positive cases.About 23 (43.4%) of the C. auris group were above 65 years old. Most cases of C. auris group were hospital-acquired (49, 92.5%). The highest number of positive cases were found in urine samples. The demographic and clinical profiles of the C. auris and non-auris groups candidemia were largely similar, except for differences in antifungal use history and ICU requirements. Notably, the C. auris group had a significantly lower history of antifungal use and a lower ICU requirement compared to the non-auris group. The study also highlighted the higher mortality rate associated with candidemia. While mortality was higher in the non-auris group, the difference was not statistically significant. Conclusions The findings of the study suggest that while C. auris poses a serious threat, particularly in hospital settings; the clinical and demographic factors influencing its spread and impact are complex and warrant further investigation. Understanding these factors is crucial for developing effective strategies to prevent and manage C. auris infections, particularly in vulnerable patient populations.

Two outbreaks and sporadic occurrences of Candida auris from one hospital in China: an epidemiological, genomic retrospective study.

To investigate the clinical relevance, origin, transmission, and resistance of Candida auris (C. auris) isolates from two outbreaks and sporadic occurrences from one hospital in China. A total of 135 C. auris isolates were collected. Clinical characteristics were obtained and antifungal susceptibility testing (AFST) was performed using the method of broth microdilution. Phylogenetic tree, WGS analysis, and single nucleotide polymorphisms (SNPs) were used to determine the origin, transmission, and resistance mechanisms. A total of 31 patients (91.2%, 31/34) received invasive medical procedures and 13 patients (38.2%, 13/34) had antifungal agents before C. auris infection/colonization, except one patient whose clinical information was missing. Only 4 cases of C. auris candidemia were observed. 18 patients died, 13 patients recovered, and the outcomes of 3 patients were not available. A total of 35 C. auris isolates, which were successfully cultivated and the first isolated or harbored specific drug-resistant phenotype from each patient, were selected to be sequenced and further analyzed. C. auris isolates presented low genetic variability and belonged to clade I, possibly originating from BJ004-H7 in Beijing. All 35 isolates were resistant to Fluconazole (FCZ) and amphotericin B (AMB), and 3 isolates were resistant to caspofungin (CAS). Mutations in ERG11 and FKS1 were linked to reduced azole and echinocandin susceptibility, respectively. Two outbreaks of highly clonal, multidrug-resistant C. auris isolates within the medical facility were reported. The intensive performance of disinfection measures helped block in-hospital transmission. Understanding the epidemiology, drug resistance and management of C. auris will be helpful for implementing effective infection control and treatment strategies.

Comparative efficacies of the three echinocandins for Candida auris candidemia: real world evidence from a tertiary centre in India.

Though echinocandins are the first line of therapy for C. auris candidemia, there is little clinical data to guide the choice of therapy within this class. This was the first study to compare the three echinocandins in terms of efficacy and outcomes for C. auris candidemia. This was a retrospective analysis of 82 episodes of candidemia caused by C. auris comparing outcomes across the three echinocandins. Majority patients in our study were treated with micafungin. Susceptibility rates were the lowest for caspofungin (35.36% resistance), with no resistance reported for the other two echinocandins. When a susceptible echinocandin was chosen, caspofungin resistance was not a factor significantly associated with mortality. Also, when a susceptible echinocandin was used for therapy, the choice within the class did not affect clinical cure, microbiological cure, or mortality (P>0.05 for all). Failure to achieve microbiological cure (P=0.018) and receipt of immune-modulatory therapy (P=0.01) were significantly associated with increased mortality. Significant cost variation was noted among the echinocandins. Considering the significant cost variation, comparable efficacies can be reassuring for the prescribing physician.

First report of Candida auris in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia

ABSTRACT Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.

Risk factors, antifungal susceptibility, complications, and outcome of Candida auris bloodstream infection in a tertiary care center in the western region of Saudi Arabia

BackgroundCandida auris, an emerging multidrug-resistant fungus species that grows as yeast, causes bloodstream infection, and is associated with high mortality rates. In this study, we identified risk factors associated with C. auris bloodstream infection, antifungal susceptibility pattern, complications, and outcome of the infection. MethodsThis single-center cross-sectional retrospective study was conducted at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia, which included all patients 18 years or above who have had one or more blood cultures for C. auris between January 2021 and December 2022. We aimed to identify the risk factors associated with C. auris bloodstream infection, antifungal susceptibility patterns, complications, and outcomes at our center. ResultsForty-six patients with C. auris-positive blood cultures were included. All the patients had healthcare-associated infections. The mean age was 64.67 years, and the majority of patients were male (73.9 %). The most common concomitant hospital-acquired infections were skin and soft tissue infections (37 %), followed by hospital-acquired pneumonia (34.8 %) and intra-abdominal infections (26.1 %). The mean total white blood cell count, procalcitonin, and C-reactive protein was 10.5 ± 5.99 × 109/L, 2.63 ± 4.82 μg/L, and 90.3 ± 64.1 mg/L, respectively. Hypertension (73.9 %) was the most common comorbidity, followed by diabetes mellitus (58.7 %) and renal dysfunction (54.3 %). Risk factors associated with C. auris candidemia included antibiotic use (91.3 %), especially for > 14 days (78.3 %), C. auris colonization (60.9 %), use of central venous catheters, especially when the catheter was in place for >30 days (80.4 %), ICU admission in the last 30 days before C. auris-positive blood culture (93.5 %), especially for more than two weeks (76.1 %), mechanical ventilation (89.1 %), total parenteral nutrition (13 %), previous intra-abdominal surgery (30.4 %), and immunosuppressive therapy (56.5 %). A total of 97.8 % of C. auris isolates were resistant to fluconazole and 17.4 % were resistant to amphotericin B. Endocarditis and endophthalmitis were reported in one (2.2 %) patient each. The all-cause mortality at 30 days was 47.8 %. ConclusionOur study is one of the few studies available globally on C. auris bloodstream infection that investigated risk factors, antifungal susceptibility, complications, and outcomes. A thorough screening and risk assessment strategy should aid infection control, preventing it from becoming a major concern in the future.

Candida auris Blood stream infection- a descriptive study from Qatar

BackgroundCandida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality.ObjectiveTo describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection.MethodsWe conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described.ResultsWe identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control.ConclusionOur study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes.

Nosocomial infection of C. auris in COVID-19 Intensive Care Unit in Türkiye and Phylogenetic Analysis of Isolates.

The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates. C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades. The mean growth time in blood cultures was 38.8h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I). This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia.

Candida auris from colonisation to candidemia: A four-year study.

Candida auris has become a worrisome multi-drug resistant healthcare-associated pathogen due to its capacity to colonise patients and surfaces and to cause outbreaks of invasive infections in critically ill patients. This study evaluated the outbreak in our setting in a 4-year period, reporting the risk factors for developing candidemia in previously colonised patients, the therapeutic measures for candidemia and the outcome of candidemia and colonisation cases among all C. auris isolates and their susceptibility to antifungals. Data were retrospectively collected from patients admitted to Consorcio Hospital General Universitario de Valencia (Spain) from September 2017 to September 2021. A retrospective case-control study was designed to identify risk factors for developing C. auris candidemia in previously colonised patients. C. auris affected 550 patients, of which 210 (38.2%) had some clinical sample positive. Isolates were uniformly resistant to fluconazole, 20 isolates were resistant to echinocandins (2.8%) and four isolates were resistant to ampfotericin B (0.6%). There were 86 candidemia cases. APACHE II, digestive disease and catheter isolate were proven to be independent risk factors for developing candidemia in previously colonised patients. Thirty-day mortality rate for C. auris candidemia cases was 32.6%, while for colonisation cases was 33.7%. Candidemia was one of the most frequent and severe infections caused by C. auris. The risk factors identified in this study should help to detect patients who are at more risk of developing candidemia, as long as an adequate surveillance of C. auris colonisation is performed.

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15-9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24-1.97) and 36.4% and 42.3% (0.77; 0.27-2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes.

P184 Candida auris candidemia in COVID-19 and post-COVID-19 patients in a tertiary care hospital in North India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction Candida spp. accounts for 70%-80% of invasive bloodstream fungal infections. It is most commonly spread in long-term care facilities, caring for people with severe medical conditions. Patients hospitalized for COVID-19 are at risk for healthcare-associated infections like candidemia. Candida auris is an emerging, multidrug-resistant, healthcare-associated fungal pathogen. Candida auris is currently one of the most common clinical fungal pathogens, causing nosocomial infections. Due to its higher drug-resistance rate, C. auris is more difficult to treat, requires longer hospitalization periods, and results in higher morbidity and mortality than other Candida species.Aim and ObjectivesTo analyze the risk factors associated with C. auris candidemia in COVID-19 and post-COVID-19 patients at tertiary care center.Material and MethodsWe prospectively analyzed all positive blood samples which were received in the Microbiology department at SGPGI, Lucknow for a period of 1 year (March 2020-March 2021). Blood samples were inoculated and cultured in BACTEC Bottles (BD) and incubated for 5 days at 37°C. The bottles which flagged positive, a Gram's stain was performed and were sub-cultured on SDA for isolation of yeast colonies. Isolated yeasts were identified by phenotypic method and confirmed by MALDI-TOF MS. Demographics details of the patients were collected and recorded. The significant associated risk factors with C. auris candidemia were analyzed.ResultsA total of 13 000 blood samples were received during the 1-year study period from different departments of the hospital.1.25% (n = 163) of the blood culture samples were positive for candidemia. Out of 163 Candida culture-positive blood samples, 27.61% (n = 45) were C. auris. A total of 64% (n = 29) C. auris candidemia was seen in non-COVID-19 patients, 31.1% (n = 14) in COVID-19 patients, and two patients had a history of post-COVID-19 infection. The associated risk factors included the use of broad-spectrum antibiotics, intravenous catheterization, underlying respiratory illness, mechanical ventilation, use of steroids, and dialysis. A total of 46.6% (n = 21) mortality was seen with C. auris candidemia.Conclusions Candida auris candidemia continues to be a threat in hospitalized patients. This study shows prevalence of C. auris candidemia in COVID-19 and post-COVID-19 patients with 47% mortality. Candida auris is continuously reported from different departments in our institute, especially from intensive care units with high morbidity and mortality. An alertness, awareness and infection control practices by the healthcare personnel will help in early diagnosis and appropriate antifungal therapy and control the spread of C. auris.

P050 Candida auris and non- auris candidemia in adult patients in a tertiary care set-up, New Delhi, India

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesThe aim of this study was to determine the species distribution, compare Candida auris and non-C. auris candidemia risk factors and antifungal susceptibility pattern of candidemia cases in adult patients at a tertiary care hospital, New Delhi, India.Materials and Methods Candida species identification was performed by phenotypic methods, VITEK (Biomerieux, France), and DNA sequencing (PGIMER, Chandigarh). The antifungal susceptibility was performed by broth microdilution method as per CLSI M27-A4 guidelines 2017.ResultsOut of 1274 blood samples, 70 samples (5.5%) yielded the growth of Candida species. There was a predominance of NAC spp. over C. albicans in candidemia patients. C. auris (12.85%, 9/70) and non-auris candidemia (87.14%, 61/70) was isolated in this study. In non-auris candidemia, C. tropicalis (28.57%, 20/70) was the predominant Candida species followed by C. parapsilosis (22.85%, 16/70), C. glabrata (14.28%, 10/70). Rare species among NAC spp. included C. mesorugosa, C. lusitaniae, C. krusei and C. haemulonii were isolated. The most common predisposing factor for C. auris and non-auris candidemia was urinary catheter (72.85%, 51/70) followed by an increased period of hospitalization (42.85%, 30/70), diabetes mellitus (21.5%, 15/70), etc. The significantly associated risk factor associated with C. auris was diabetes mellitus (P = .02). The overall resistance was 22.57% to all antifungal drugs. The multidrug resistance (MDR) was noted in 5.71% of isolates.ConclusionsEarly identification of risk factors, Candida speciation, and timely management are crucial for the outcome of candidemia cases. Non-albicans species were predominant over C. albicans depicting the change in the epidemiology and emergence of MDR Candida spp. like C. auris, C. glabrata, C. mesorugosa, C. lusitaniae, and Pichia kudriavzevii (C. kruseii). This warrants routine antifungal susceptibility testing (AFST) and close monitoring. The knowledge of local epidemiological profiles of Candida spp., accurate species identification, and their antifungal susceptibility is crucial for overall patient management.

The first invasive Candida auris infection in Taiwan

ABSTRACT Candida auris, a multidrug resistant pathogenic yeast, has spread worldwide and caused several outbreaks in healthcare settings. Here, we report the first case of C. auris candidemia in Taiwan in a patient with a two-month history of hospitalization in Vietnam. We performed further investigation on the isolate from the present case as well as the previously reported C. auris isolate identified from a wound in 2018 in Taiwan, which was the first case reported in Taiwan. Both C. auris isolates were found to be susceptible to fluconazole, amphotericin B, and echinocandins. Additionally, mutations in ERG11 or FKS1 were not detected in either isolate. Microsatellite genotyping revealed that both isolates belonged to the South Asian clade. In recent years, C. auris has emerged as a global concern, and differences in clades and susceptibility patterns mandate further awareness and systematic surveillance.

Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review.

Background Candida auris is an emerging multidrug‐resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID‐19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID‐19 patients.ObjectivesThe present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID‐19 patients.MethodsMEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021.ResultsA total of 97 cases of C. auris were identified in COVID‐19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non‐candidemia cases) in COVID‐19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad‐spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non‐candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%.ConclusionThis study shows that the prevalence of C. auris infections remains unchanged in the COVID‐19 pandemic. Hospital‐acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.

The Dominance of Candida auris: A Single-center Experience of 79 Episodes of Candidemia from Western India.

IntroductionInvasive candidiasis is a serious infection seen in hospitalized or immunocompromised patients. Mortality rates for candidemia can be as high as 30–60%. Candida auris is an emerging species of Candida and is increasingly becoming a global public health problem.MethodsThis was a retrospective observational study, in which we analyzed 79 episodes of candidemia. Blood cultures were done using the Bactec™ FX blood culturing instrument (Becton, Dickinson and Company Sparks, Maryland, USA). Species identification was done using VITEK® 2 YST panels (bioMérieux Inc., Durham, North Carolina, USA). Antifungal susceptibility testing was performed using VITEK® 2 AST-YSO8 panels (bioMérieux Inc., Durham, North Carolina, USA).ResultsAmong the 79 episodes, the most common species was found to be C. auris (43.03% of all the episodes). Candida tropicalis was found to be the second most common species in patients admitted to our hospital with candidemia. All the isolates of C. auris were resistant to fluconazole, while 32.35 % of the isolates were also resistant to amphotericin B. Crude mortality in patients with C. auris candidemia was higher than the crude mortality for the other species.ConclusionThis is the first study from India where C. auris was seen as the most predominant species among patients admitted with candidemia. This is a serious issue given the high rates of fluconazole resistance, mortality, and cost of therapy associated with C. auris bloodstream infections. Urgent attention needs to be diverted to infection control practices and antimicrobial stewardship programs.How to cite this articlePrayag PS, Patwardhan S, Panchakshari S, Rajhans PA, Prayag A. The Dominance of Candida auris: A Single-center Experience of 79 Episodes of Candidemia from Western India. Indian J Crit Care Med 2022;26(5):560–563.

Candida auris Candidemia in Critically Ill, Colonized Patients: Cumulative Incidence and Risk Factors.

IntroductionCandida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians.MethodsWe conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population.ResultsDuring the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was > 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia.ConclusionCandida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection.

Levels of beta-D-glucan in Candida auris supernatants, an in vitro and in vivo preliminary study

ObjectivesSerum (1,3)-beta-d-glucan (BDG) assay is a non–culture-based test recommended for the diagnosis of invasive candidiasis owing to its faster results and higher sensitivity than blood cultures. Its performance might vary for different Candida species. The aim of this study was to determine in vitro levels of BDG in Candida auris culture supernatants and evaluate BDG levels in patients with C. auris candidemia sustained by these stains. MethodsC. auris strains were collected from blood cultures of patients who had a concomitant (–24 to +72 hours) serum BDG test (Fungitell assay). Supernatants of broth media culture of C. auris strains and two Candida albicans (controls) strains were prepared and tested for BDG. ResultsTen C auris strains were included. Supernatants of two C. albicans considered as controls had a mean BDG level of 1155 pg/mL (considered 100% reactivity). The median BDG level in supernatants of C. auris strains was 275 pg/mL (IQR 165–523 pg/mL), with a median reactivity of 24% (range 6%–72%). In vivo, the median BDG level was 129 pg/mL (IQR, 28–199 pg/mL). Sensitivity of BDG for C. auris candidemia was 60%. All patients received antifungal treatment with an echinocandin initiated a median of 2 days (IQR –8 to 0) before blood collection for BDG. DiscussionOur C. auris strains released lower amounts of BDG when compared to C. albicans. Clinical implications include lower sensitivity of serum BDG for the diagnosis of C. auris candidemia with a consequent impact on management protocols in settings with high prevalence of this species.

Candida auris Bloodstream Infection Induces Upregulation of the PD-1/PD-L1 Immune Checkpoint Pathway in an Immunocompetent Mouse Model.

ABSTRACTCandida auris is a globally spreading yeast pathogen causing bloodstream infections with high mortality in critically ill patients. The inherent antifungal drug resistance of most C. auris isolates and threat of multidrug-resistant strains create a need for adjunct immunotherapeutic strategies. While C. albicans candidemia was shown to induce immune paralysis and activation of inhibitory immune checkpoints, in vivo data on host responses to C. auris bloodstream infection are lacking as is an immunocompetent murine infection model to study the immunopathology and immunotherapy of C. auris sepsis. Therefore, herein, we developed an immunocompetent C. auris sepsis model by intravenously infecting C57BL/6 mice with 1.5 × 108 to 8 × 108 yeast cells of aggregate-forming (AR-0384) and nonaggregative (AR-0381) C. auris reference isolates. Both isolates caused reproducible, inoculum-dependent increasing morbidity, mortality, and fungal burden in kidney tissue. Notably, morbidity and mortality outcomes were partially decoupled from fungal burden, suggesting a role of additional modulators of disease severity such as host immune responses. Flow cytometric analyses of splenic immune cells revealed significant upregulation of the programmed cell death protein 1 (PD-1) on T cells and its ligand PD-L1 on macrophages from mice infected with C. auris AR-0384 compared to uninfected mice. PD-L1 expression on macrophages from AR-0384-infected mice strongly correlated with fungal tissue burden (Spearman’s rank correlation coefficient [ρ] = 0.95). Altogether, our findings suggest that C. auris sepsis promotes a suppressive immune phenotype through PD-1/PD-L1 induction, supporting further exploration of PD-1/PD-L1 blockade as an immunotherapeutic strategy to mitigate C. auris candidiasis.IMPORTANCE Health authorities consider Candida auris to be one of the most serious emerging nosocomial pathogens due to its transmissibility, resistance to disinfection procedures, and frequent antifungal drug resistance. The frequency of multidrug-resistant C. auris isolates necessitates the development of novel therapeutic platforms, including immunotherapy. However, in vivo data on host interactions with C. auris are scarce, compounded by the lack of reliable immunocompetent mammalian models of C. auris candidemia. Herein, we describe a C. auris sepsis model in immunocompetent C57BL/6 mice and demonstrate reproducible and inoculum-dependent acute infection with both aggregate-forming and nonaggregative reference isolates from different clades. Furthermore, we show that C. auris sepsis induces upregulation of the PD-1/PD-L1 immune checkpoint pathway in infected mice, raising the potential of a therapeutic benefit of immune checkpoint blockade. Our immunocompetent model of C. auris sepsis could provide a facile preclinical platform to thoroughly investigate immune checkpoint blockade and combination therapy with antifungals.

709. Risk Factors for Candida auris Candidemia: Results from a Multicenter Case-Control Study

BackgroundThe emergence of Candida auris as a global pathogen has been described as a serious global threat by the CDC. It has caused outbreaks in healthcare settings as it is transmissible between patients. The risk factors for candidemia caused by C. auris may be different than candidemia caused by other Candida spp.MethodsWe performed a multicenter, retrospective case-control study at three hospitals in Brooklyn, New York between 2016 and 2020. Patients with at least one positive blood culture for Candida spp who were started empirically on an antifungal within 24 hours of blood culture positivity were included in the study. Subsequent cases in the same patient were excluded unless separated by at least 90 days from the initial case. Similar variables such as antibiotics and antifungals within the same drug class were compressed into one variable. Variables with a p-value ≤ 0.05 on univariate analysis were entered into a multivariable analysis with a p-value ≤ 0.05 considered to be statistically significant.Results84 cases of C. auris candidemia and 105 cases of candidemia caused by other Candida spp were included in the analysis. The most common species of other Candida spp was C. glabrata (N=33, 31.7%) followed by C. albicans (N=32, 30.4%). In the multivariable model, the strongest risk factor for C. auris candidemia was prior infection or colonization with C. auris (aOR 17.5; 95% CI, 1.60-192.93; P = 0.019) followed by prior infection or colonization with multidrug-resistant bacteria (aOR 6.97; 95% CI 1.49-32.74, P = 0.014). A history of peripheral vascular disease (PVD) (aOR 7.78; 95% CI 1.34-45.34, P = 0.023), cerebrovascular disease (CVA) (aOR 4.24; 95% CI 1.18-15.20, P = 0.027) and hemiplegia (aOR 6.43; 95% CI 1.19-34.85, P = 0.031) were also statistically significant. These risk factors remained significant analyzing only patients without any history of C. auris.ConclusionThese data suggest that in hospitalized patients with candidemia, a history of colonization or infection with C. auris, prior infection or colonization with multidrug-resistant bacteria, as well as a history of PVD, CVA, and hemiplegia are associated with C. auris candidemia. Disclosures Samuel Simon, PharmD, Accelerate Diagnostics (Employee)

A case of Candida auris candidemia in Xiamen, China, and a comparative analysis of clinical isolates in China

ABSTRACT The recently emerged fungal pathogen Candida auris often displays resistance to one or more antifungal drugs. Its infections have been identified in at least 40 countries on six continents to date. Here we report a case of C. auris candidemia in a patient in Xiamen, a city in south China. We also review currently reported cases of C. auris infection in China and compare the genetic and biological features of C. auris strains isolated from this country. Our phylogenetic analysis indicates that there are at least two C. auris genetic clades present in China (the South African clade and the south Asian clade) that display opposite mating type loci (one is MTL a and the other is MTLα). We also found that there are several distinct features among the clinical isolates studied, including the expression of virulence factors, antifungal susceptibilities, and cellular morphologies, and that these features could be associated with the mating-type of the isolate. For example, C. auris MTL a isolates generally secreted higher levels of secreted aspartyl proteases (Saps) at ambient environmental temperatures. Taken together, this study demonstrates that C. auris clinical isolates from China exhibit diversity in both biological and genetic features.

C. auris and non-C. auris candidemia in hospitalized adult and pediatric COVID-19 patients; single center data from Pakistan

26 candidemia cases (4 Candida auris;22 non-C. auris) in COVID-19 patients (April-December 2020) are reported from Pakistan. Compared to non-C. auris, C. auris candidemia patients had higher prior antifungal exposure, longer hospital stay, higher rates of MDR bacteria and Candida colonization.