Auris Infection Research Articles

2043. In Vitro Activity of Manogepix Against 2,810 Fungal Isolates from the SENTRY Surveillance Program (2020-2021) Stratified by Infection Type

Abstract Background Manogepix is a new antifungal with a novel mechanism of action and potent in vitro activity against Candida (except C. krusei), Aspergillus, and rare mold isolates. The manogepix prodrug fosmanogepix is in Phase 2 development for the treatment of invasive mold infections caused by Aspergillus and rare molds (NCT04240886) and has completed Phase 2 studies for candidemia (NCT03604705) and C. auris (NCT04148287) infections. We evaluated the in vitro activity of manogepix and comparators against 2,810 geographically diverse fungal isolates collected in the SENTRY Surveillance Program during 2020-2021 and stratified them by infection type. Methods Antifungal susceptibility testing of manogepix and comparator agents was conducted according to CLSI M27 (2017) and M38 (2017) guidelines. Fungal surveillance isolates were collected from medical centers located in North America (30 sites; 37.9%), Europe (30 sites; 38.4%), Asia-Pacific (11 sites; 14.7%), and Latin America (6 sites; 9.0%). Infection sites included bloodstream infections (BSI; 48.3%), pneumonia in hospitalized patients (PIHP; 19.9%), skin and skin structure infections (SSSI; 7.8%), urinary tract infections (UTI; 3.1%), intra-abdominal infections (IAI; 1.6%), and other infection types (19.3%). Results Manogepix demonstrated potent in vitro activity against Candida spp. isolates (MIC50/90, 0.004-0.03/0.008-0.06 mg/L) regardless of infection type (Table). Similarly, manogepix was highly active against 534 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L). Manogepix was active against 53 Cryptococcus neoformans var. grubii (MIC50/90, 0.25/1 mg/L), 19 Fusarium spp. (MEC50/90, 0.015/0.06 mg/L), 12 Lomentospora prolificans (MEC50/90, 0.03/0.06 mg/L), and 17 Scedosporium spp. isolates (MEC50/90, 0.06/0.12 mg/L). Conclusion Manogepix showed potent in vitro activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and rare molds, including Fusarium spp., L. prolificans, and Scedosporium spp. isolates. Notable activity was also demonstrated by manogepix against C. auris isolates. Further clinical development of fosmanogepix in difficult-to-treat, resistant fungal infections is warranted. Disclosures Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

Candida auris and COVID-19: A health threatening combination.

Since its first emergence in December 2019, due to its fast distribution throughout the world, SARS-COV-2 become a global concern. With the extremely increased number of hospitalized patients, this situation provided a potential basis for the transmission of nosocomial infections. Candida auris is a multidrug-resistant pathogen with improved transmission dynamics and resistance traits. During the worldwide spread of COVID-19, cases or outbreaks of C. auris colonization or infection have been reported. Resistance to antifungal drugs has been observed in the causative agents of the majority of such cases. The focus in this review is on COVID-19-associated C. auris infections (case studies/outbreaks) and the pandemic's potential effect on antifungal drug resistance.

Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021.

The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.

Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information.

Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.

Fungicidal activity of human antimicrobial peptides and their synergistic interaction with common antifungals against multidrug-resistant Candida auris.

Emergence of Candida auris, a multidrug-resistant yeast, demonstrates the urgent need for novel antifungal agents. Human antimicrobial peptides (AMPs) are naturally occurring molecules with wide spectrum antimicrobial activity, particularly against a variety of fungi. Therefore, this study examined the antifungal activity of seven different human AMPs against C. auris following the CLSI guidelines. The antifungal activity was further assessed using time kill curve and cell viability assays. For combination interaction, effectiveness of these peptides with three antifungals, fluconazole, amphotericin B, and caspofungin was done following standard protocols. To elucidate the antifungal mechanism, the effects of peptides on membrane permeability were investigated using propidium iodide staining method and confocal imaging. Antifungal susceptibility results showed that all the examined peptides possessed fungicidal effect against C. auris at different levels, with human β-defensin-3 being the most potent antifungal with MIC values ranging from 3.125 to 12.5µg/ml. Time kill curves further confirmed the killing effect of all the tested peptides. Viability assay showed a significant decrease in the percentage of viable cells exposed to different inhibitory and fungicidal concentrations of each peptide (p < 0.01). Furthermore, peptides showed mostly synergistic interaction when combined with conventional antifungal drugs, with caspofungin showing 100% synergy when combined with different AMPs. As antifungal mechanism, peptides disrupted the membrane permeability at concentrations that correlated with the inhibition of growth. Overall, the findings of this study point towards the application of the tested peptides as a monotherapy or as a combination therapy with antifungal drugs to treat multidrug-resistant C. auris infections.

Small molecules for combating multidrug-resistant superbug Candida auris infections.

Candida auris is emerging as a major global threat to human health. C. auris infections are associated with high mortality due to intrinsic multi-drug resistance. Currently, therapeutic options for the treatment of C. auris infections are rather limited. We aim to provide a comprehensive review of current strategies, drug candidates, and lead compounds in the discovery and development of novel therapeutic agents against C. auris. The drug resistance profiles and mechanisms are briefly summarized. The structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds will be illustrated in detail, and perspectives for guiding future research will be provided. We hope that this review will be helpful to prompting the drug development process to combat this fungal pathogen.

Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review.

The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search in MEDLINE, EMBASE, Web of Science, and Scopus up to 27 June 2022 was conducted to find relevant articles reporting data of in vitro activity and in vivo efficacy of investigational antifungals against C. auris. These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. From 592 articles retrieved in the primary search, 27 met the eligibility criteria. The most studied agent was manogepix/fosmanogepix (overall MIC90: 0.03 mg/L), followed by ibrexafungerp (overall MIC90: 1 mg/L) and rezafungin (overall MIC mode: 0.25 mg/L), while VT-1598 and ATI-2307 were the least explored drugs against C. auris. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential.

Candida auris: A Mini Review on Epidemiology in Healthcare Facilities in Asia.

Candida auris, a newly emerging healthcare-associated yeast pathogen from the Metschnikowiaceae family, was first described in the ear canal of an elderly Japanese patient in 2009. The yeast is one of the causative agents of candidemia, which has been linked with nosocomial outbreaks and high mortality rates in healthcare facilities worldwide. Since its first isolation, the occurrence of C. auris in six continents has becomes a grave concern for the healthcare professionals and scientific community. Recent reports showed the identification of five geographically distinct clades and high rates of antifungal resistance associated with C. auris. Till date, there are no effective treatment options, and standardized measures for prevention and control of C. auris infection in healthcare facilities. This leads to frequent therapeutic failures and complicates the eradication of C. auris infection in healthcare facilities. Thus, this review focuses on the recent understanding of the epidemiology, risk factors, diagnosis, transmission and prevention and control strategies of C. auris infection in healthcare facilities in Asia.

Melanization of Candida auris Is Associated with Alteration of Extracellular pH.

Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of C. auris, we investigated whether it produces the common fungal virulence factor melanin. Melanin is a black-brown pigment typically produced following enzymatic oxidation of aromatic precursors, which promotes fungal virulence through oxidative stress resistance, mammalian immune response evasion, and antifungal peptide and pharmaceutical inactivation. We found that certain strains of C. auris oxidized L-DOPA and catecholamines into melanin. Melanization occurred extracellularly in a process mediated by alkalinization of the extracellular environment, resulting in granule-like structures that adhere to the fungus’ external surface. C. auris had relatively high cell surface hydrophobicity, but there was no correlation between hydrophobicity and melanization. Melanin protected the fungus from oxidative damage, but we did not observe a protective role during infection of macrophages or Galleria mellonella larvae. In summary, C. auris alkalinizes the extracellular medium, which promotes the non-enzymatic oxidation of L-DOPA to melanin that attaches to its surface, thus illustrating a novel mechanism for fungal melanization.

Candida auris, a singular emergent pathogenic yeast: its resistance and new therapeutic alternatives.

Nowadays, fungal infections affect millions of people across the world. Candida auris, a new emergent yeast, is a worrisome pathogen because it associates with a high rate of incidence and prevalence, including in the nosocomial environment. The hard identification, the phenotypic plasticity, and the easy adaptation to stressful conditions are some of the C. auris traits that render this latest yeast singular challenging. C. auris infections have already been reported from more than 30 countries and are associated with high mortality rates. This is the result from rapid transmission and the difficulty of prevention, control, and eradication. There are several factors related to the high virulence of C. auris, such as the multidrug resistance, biofilm development, and the ability to escape the response of the innate immune system. So, C. auris infections are a serious and alarming problem, not only because of the high pathogenicity of the fungal agent but also because of the low effectiveness of the treatments available. Although new formulations have been developed against C. auris strains, a better understanding is essential to efficiently treat, prevent, and control C. auris infections.

Challenges and opportunities in stewardship among solid organ transplant recipients with Candida auris bloodstream infections.

Candida auris is an emerging nosocomial pathogen worldwide. However, there has been little published on the management of C. auris in solid organ transplant recipients. A single-center, retrospective cohort study was conducted to evaluate C. auris bloodstream infections in solid organ transplant recipients between January 2020 and December 2021. Patient-related and outcomes data were extracted from electronic medical records. Of the 42 patients identified with C. auris bloodstream infections, five were in solid organ transplant recipients (1 heart, 3 liver, and 1 combined liver-kidney). The median time to fungemia from hospital admission was 43 days, and the median time to fungemia from transplant was 18 days. All patients received micafungin as initial treatment, at a median of 6 hours from pathogen detection. Four patients achieved blood clearance, two patients had persistent fungemia, and two patients developed secondary complications from hematogenous spread. One patient died, resulting in a mortality rate of 20%. Solid organ transplant recipients are at high risk for developing C. auris bloodstream infections. In order to prevent graft loss and mortality, best practices for the management of C.auris should include rapid screening, diagnosis, and treatment. While echinocandins are considered first-line, antifungal selection should be based on susceptibilities and site of infection. Data to support routine use of combination therapy are lacking, however there may be a role for refractory cases. Prevention efforts against C. auris infection are especially important given the lack of effective decolonization strategies. For transplant recipients, hospitals should seek opportunities to restore patients' gut microbiome by curtailing unnecessary hospital procedures and inappropriate antimicrobial use. Further research and national guidelines are needed to better direct stewardship in this field.

Caspofungin Affects Extracellular Vesicle Production and Cargo in Candida auris.

Antifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, Candida auris stands out for commonly being highly resistant to antifungal drugs, and some isolates are pan-resistant. The rate of mortality linked to C. auris infections varies from 28% to 78%. In this study, we characterized C. auris extracellular vesicles (EVs) in the presence of caspofungin, an echinocandin, which is the recommended first line antifungal for the treatment of infections due to this emerging pathogen. Furthermore, we also analyzed the protein and RNA content of EVs generated by C. auris cultivated with or without treatment with caspofungin. We observed that caspofungin led to the increased production of EVs, and treatment also altered the type and quantity of RNA molecules and proteins enclosed in the EVs. There were distinct classes of RNAs in the EVs with ncRNAs being the most identified molecules, and tRNA-fragments (tRFs) were abundant in each of the strains studied. We also identified anti-sense RNAs, varying from 21 to 55 nt in length. The differentially abundant mRNAs detected in EVs isolated from yeast subjected to caspofungin treatment were related to translation, nucleosome core and cell wall. The differentially regulated proteins identified in the EVs produced during caspofungin treatment were consistent with the results observed with the RNAs, with the enriched terms being related to translation and cell wall. Our study adds new information on how an echinocandin can affect the EV pathway, which is associated with the yeast cell being able to evade treatment and persist in the host. The ability of C. auris to efficiently alter the composition of EVs may represent a mechanism for the fungus to mitigate the effects of antifungal agents.

P438 Epidemiology, risk factor analysis and management of invasive Candida auris infections in tertiary care hepatobiliary center in India

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectives Candida auris (C. auris) infections are associated with misidentification, intrahospital transmission, poor treatment outcomes, and higher mortalities. Prompt detection, earlier initiation of therapy and effective surveillance can curtail C. auris in hospitals. We aimed to study epidemiology, risk factors, and therapeutic management of invasive infections caused by C. auris in patients with hepatobiliary diseases.MethodsSingle-center, prospective study of patients with suspected invasive fungal infections between January2017-December 2021 in the patients with hepatobiliary diseases. Demographics, comorbidities, and laboratory variables were recorded. The positive yeast cultures were identified by VITEK 2 (Biomerieux, India) and antifungal sensitivity confirmed by Broth microdilution in accordance with CLSI guidelines. The final outcomes considered were mortality within 1 month after diagnosis or discharge of the patient with stable parameters.ResultsTotal of 189 isolates of C. auris from 73 patients, blood 25 (13.2%), abdominal fluids 29 (15.3%), urine 90 (47.6%), respiratory 7 (3.6%), liver abscess 2 (1.05%), pancreatic abscess 1 (0.5%), and wound infections 3 (1.5%). Underlying disease was chronic liver disease 49 (68%), 15 (20%) post liver transplant patients, acute on chronic liver failure 5 (7%), acute liver failure 2 (3%), acute pancreatitis 1 (1.3%), and pancreatic neuroendocrine tumor 1 (1.3%). 18 (25%) patients were discharged, the mortality was 54 (74.04%). Risk factors were MELD 40 (P .04), Child C (P .05), and CTP score above 12. Prior use of steroids (P .02), neutropenia (P .03), prolonged hospital stay (P .029), the use of broad-spectrum antibiotics ˃7 days (P .05) were the risk factors significantly associated with the development of C. auris infections, and higher mortality. Co-morbidities, acute renal failure, diabetes, and hepatitis infection were not significantly associated with mortality. The antifungal resistance: fluconazole 68.42%, voriconazole 14.03%, flucytosine 59.64%, and amphotericin B 28% with no resistance to caspofungin and micafungin.ConclusionOur study depicts the spectrum of invasive infections caused by C. auris, its prevalence, risk factors, and therapeutic options. The presence of risk factors, steroid use, neutropenia, broad-spectrum antibiotic use, and a hospital stay of ˃7 days should prompt toward escalating diagnostic measures for rapid identification of C. auris for early initiation of therapy. Active screening of patients with risk factors can also reduce mortality. The study results also help to guide empiric therapy with echinocandins as azoles and amphotericin B show high resistance in these isolates.

P385 Candida auris: a growing threat to global health

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Background and ObjectivesThe emerging pathogen, C. auris, has been associated with nosocomial outbreaks in recent times. The true scale of the problem is difficult to comprehend due to several issues with the identification of C. auris using both phenotypic and molecular techniques. Most commonly, these isolates have been misidentified as C. haemulonii. Biofilm formation is strongly suggested given its association with intensive care settings, especially in patients with CVCs and long-term urinary catheters. Many isolates of C. auris have also shown raised MICs to multiple classes of antifungal agents, raising the possibility of pan-drug resistance.ObjectiveTo study the demographic characteristics, risk factors, and outcomes in patients with C. auris infection.MethodologyThis is a retrospective study from a tertiary care hospital (JPNATC, AIIMS) including all patients from the time period of 2018-2022 that showed growth of C. auris in any site. C. auris was identified using conventional methods (pale-pink growth on chromogenic medium, no pseudohyphae on germ-tube test, growth in presence of 10% NaCl) and VITEK-2. To reduce the misidentification and the intertest variability, the results were confirmed with MALDI-TOF. The risk factors and other patient information were taken from the HIS. Statistical analysis was performed.ResultsDuring the study period, a total of 31 patients had a C. auris infection. The most common age group was 20-40 years (n = 11,44%) with a preponderance in males (n = 23,74%). A total of 74% of the infections were found in blood, which was the most common site of infection followed by urine (10%). The other sites were pus-from-wound (n = 2), groin, nailbeds, and CVP tip (n = 1). Most of the cases were ICU patients (86%). All the patients with candidemia due to C. auris (n = 17 100%) had CVC, had surgery within the past 30 days, and were on broad-spectrum antibiotics and TPN. 71% (n = 12) had a history of immunosuppression and 18% (n = 14) had a history of prior antifungal therapy. Although 100% (n = 17) had the presence of an indwelling urinary catheter, none of them had candiduria due to C. auris. No patient with C. auris infection had neutropenia. The median LOS was 34.5 days. Most of the isolates were resistant to fluconazole (n = 13,93%), amphotericin B (n = 13,93%), voriconazole (n = 6,55%), flucytosine (n = 10,71%). A total of 87% (n = 12,87%) of isolates were sensitive to caspofungin and micafungin by VITEK-2 (limitation of this study). In all, 28% (n = 7) of the patients died whereas 40% (n = 10) were discharged. A total of 75% patients had clearing of the persistent candidemia when treated with caspofungin whereas only 25% patients had clearing of the candidemia when treated with voriconazole.ConclusionMost cases of C. auris infection were found in critical patients with the most common presentation being candidemia. The risk factors are similar to any other Candida infection. C.auris is the leading antimicrobial-resistant fungi and poses an additional burden to the healthcare system. The fungus has a high crude-mortality rate and we are running out of treatment options. A comprehensive intervention program with ongoing surveillance and good AMR practices is the need of the hour to reduce the burden of this dangerous pathogen.

P042 Identification, clinical profile, antifungal susceptibility pattern of candida auris from a tertiary care center in india

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMObjectivesTo identify the phenotypic characteristics of Candida auris.To analyze the clinical profile of Candida auris infection.To describe the antifungal susceptibility pattern of Candida auris.MethodsThe study was conducted in the Department of Microbiology in Mycology division at Sri Ramachandra Institute of Higher Education and Research from December 2019 to November 2021. The study protocol was approved by Institutional Ethics Committee. Candida species isolated from various specimens sent to the laboratory were identified by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF). The growth characteristics of C. auris were investigated on various media including Selective Auris Medium (SAM), HiChrome agar Candida and Tetrazolium reduction agar.Antifungal susceptibility testing was performed by using the Clinical and Laboratory Standards Institute broth microdilution method M27-A3. Antifungals tested were fluconazole, itraconazole, voriconazole, posaconazole, micafungin, anidulafungin, caspofungin and amphotericin B. Candida albicans American Type Culture Collection (ATCC) 22 019 was used as quality control strains.Data were collected for demographics, risk factors for candidemia, treatment, and outcome from the respective wards and ICUs.ResultsA total of 37 C. auris isolates were collected. Both adult and pediatric cases were included. The majority (23.3%) of the C. auris cases were seen in the age group of 55-64. Median age was 54 years for the adults. Among the 7 children, 6 were neonates and 1 was an infant. The most common source of isolation is urine and blood.A total of 35/37 isolates showed moderate to heavy growth on the SAM, while 2 isolates showed mild growth after 72 h. But all the other Candida species and other yeasts tested were inhibited on this medium. All the isolates of C. auris grew as cream to pinkish purple colonies on Hichrome agar Candida. On Tetrazolium reduction agar, all of them formed maroon colonies.The average duration of hospital stay was 25 days (range 4-65). A total of 35 of the patients were admitted to ICU, 8 had undergone mechanical ventilation and intubation. Central venous catheter was inserted in 9 patients and post-operative catheter placed in 6 patients; 4 patients had undergone tracheostomy and 25 of them had undergone some other invasive procedure. Total parenteral nutrition was received by 3 patients, 16 were diabetics and 11 were hypertensives. Prior antifungal exposure was present in 9 patients and 26 had received broad-spectrum antibiotics.The crude mortality rate with C. auris infection in patients was 32.43% and the attributable mortality rate, as considered by the treating physician was 10.81%.Antifungal resistance was noted to be amphotericin B (n = 15, 40.5%), fluconazole (n = 30, 81.1%), voriconazole (n = 4, 10.81%), itraconazole (n = 6, 16.21%), posaconazole (n = 5, 13.51%), caspofungin (n = 4, 10.81%). Multidrug resistance was noted in 15 (40.54%) isolates and 3 isolates (5.4%) were resistant to a drug from all three groups.Conclusion C. auris poses a great threat to immunocompromised individuals and those admitted in ICUs for long term.

P481 Antifungal vaccines: An alternative approach to combat multidrug resistance in the post-antibiotic era

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMAlexander Fleming's discovery of the antibiotic ‘Penicillin’ and many more has inspired after saving millions of lives and spared immeasurable suffering worldwide. However, he also warned about the consequences of abuse of antibiotics that could lead to the expiry of the golden age of antibiotics. Current decreasing effectiveness of antibiotics in general and antifungals in particular, evolution of new drug-resistant forms, and species and lack of commercial interests to develop new antifungals is a clear indication of a post-antibiotic era. There is an amplified warning for the pharmaceutical industries, academic and research institutions, and governments to invest the necessary resources to produce next-generation, safe and effective antifungal vaccines. Candida auris is one of the emerging pan-resistant pathogenic yeast among immunocompromised patients worldwide. Early diagnostics and vaccines are the best alternatives to handle this drug-resistant pathogen. Cell wall proteins are responsible for eliciting an immune response in the host and therefore, can be promising candidates for the development of therapeutic biomarkers and vaccines against C. auris.Antifungal susceptibility profiling against standard antifungal drugs was performed using CLSI guidelines. The cell wall proteome was characterized by using LC-MS followed by bioinformatic and functional analyses. Furthermore, the protective effect of the cell wall-associated protein against C. auris infection was evaluated in BALB/c female mice.A total of 60 proteins were predicted to be immunodominant. In vivo results demonstrated lowered fungal burden in target organs and increased survival in vaccinated mice as compared with the infection control group revealing the immunogenic property of cell wall-associated proteins.This study validates the mass-spectrometry approach to identify antigenic proteins of C. auris and the potential of these proteins to serve as biomarkers for the development of diagnostic assays and/or vaccines against infections caused by C. auris.

P418 qPCR is a useful tool for management and surveillance of hospital contacts in the context of a Candida auris infection

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives Candida auris is an emerging fungal pathogen responsible for hospital outbreaks. It represents a serious threat due to its drug resistance profile and its potential spread within healthcare facilities. Since the global alert by the CDC in 2016, specific control measures are now available to prevent the further spread of the pathogen. These measures should be implemented immediately as soon as a case is identified to prevent patient-to-patient transmission. Until recently culture was the main technique used for the detection of C. auris from patient and environmental samples. Nevertheless, PCR protocols have been reported and commercial kits are now available. Our objectives were to compare culture and PCR in routine for the management of a case of C. auris infection in a hospital setting.MethodsWe report here the case of a patient infected by C. auris following injuries in a public road traffic accident in Dubai. Following the medical evacuation and transfer of the patient to our hospital in Paris, C. auris was isolated from several surgical specimens from the elbow. Identification of the species level was initially performed by MALDI-TOF Mass spectrometry and confirmed by ITS sequencing. Antifungal susceptibility testing was performed by Etest and EUCAST. Surveillance of the index case included bi-weekly surveillance for 2 weeks and then once a week. Contacts were also screened for C. auris colonization once a week by swabbing axilla and groin. Samples were analyzed by standard mycological cultures and a specific C. auris qPCR kit (kit Fungiplex Candida auris®, Bruker).ResultsIn total 133 samples were analyzed for the patient and 52 contacts. For the index case, 14/22 samples were positive in culture for C. auris including elbow biopsies, urine, and axilla, groin, and rectal swabs. Other Candida species (C. albicans, C. krusei) were also recovered from the same samples for the patient. For the contacts, all 111 samples were negative for C. auris by culture, but retrieved several other yeast species (C. albicans, C. glabrata, C. kefyr, C. paraspsilosis, C. tropicalis, Saccharomyces cerevisiae, Trichosporon inkin, and Wickerhamomyces anomalus). By using qPCR, all culture-positive samples were positive (Ct ranged from 29.7 to 38.0, with a median at 31.4). Two culture-negative samples (one biopsy and one axillary swab) were also qPCR-positive. All samples from contacts were negative by qPCR. The strain was resistant to fluconazole (>256 μg/ml) and susceptible to all other tested antifungals (amphotericin B, flucytosine, voriconazole, and caspofungin). Whole genome sequencing of the C. auris strain is in progress to determine the clade.DiscussionThe Fungiplex C. auris qPCR kit showed good sensitivity and specificity, even for the frequent situation of samples growing with two or three Candida species. These results highlight the usefulness of the PCR for surveillance of infected patients as well as for contacts.

P223 First case of Candida auris candidemia in Manipur, Northeast India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjective Candida auris is known as an emerging ‘superbug’ because of its intrinsic resistance to one or more, sometimes to all available antifungal drugs and spreading globally. It has the ability to cause devastating nosocomial infections. In India, C. auris infection is on the rise with reports from north, south, central and eastern India. Here we present the first case of C. auris fungemia from a tertiary care hospital of Manipur in Northeast India.MethodsA 15-year-old Muslim girl was referred from a private hospital to Regional Institute of Medical Sciences (RIMS) hospital on November 19, 2021 with a history of burning epigastrium, headache, loss of appetite, shortness of breath, dry cough, fever, and generalized weakness for last 3 days. At the time of admission she was cyanotic. Family gave history of congenital heart disease and frequent visits to hospital. Echocardiogram revealed congenital cyanotic heart disease (Tetralogy of Fallot) showing large perimembranous VSD with bidirectional shunt. A complete hemogram showed neutrophilic leukocytosis with shift to left with band form, absolute monocytosis, and increased RBC count with mild anisocytosis. On November 24, 2021, 5 days after admission, her condition deteriorated and she was shifted to ICU. However, the condition of the patient deteriorated and she died on November 29, 2021 due to acute decompensated heart failure. Follow-up of other patients admitted in the same ward revealed no candidemia in next the few weeks.ResultsA single blood culture sent on November 29, 2021 was incubated in an automated blood culture system, BacT Alert and showed growth of budding yeast cells. Growth in SDA revealed it to be Candida sps. and Gram-stained smear examination revealed presence of budding yeast cells but no pseudohyphae. Germ tube test was negative. On CHROM agar, it produces pale yellow colonies at 24 h which progresses to light purple colonies around the rim at 48 h. Further processing in VITEK 2 (Biomerieux) identified it as C. auris. The isolate was sent to National Culture Collection of Pathogenic Fungi, WHO collaborating center, PGIMER and the isolate was confirmed as Candida auris by MALDI-TOF assay.Conclusion Candida auris is spreading irrespective of the level of health care. Blood culture before administration of antibiotics and in febrile sick patients cannot be underestimated. Rapid and accurate identification methods for timely diagnosis and stringent infection control measures with an emphasis on hand hygiene are important to prevent and control C. auris outbreaks.

S10.4d A unique clinical appearance of Candida auris infection in Japan

S10.4 Emerging antifungal resistant fungi, September 24, 2022, 10:30 AM - 12:00 PMIt has only been 15 years since Candida auris was reported isolated from the ear canal of a 70-year-old Japanese woman in Tokyo, and no record of an isolate corresponding to this species has been found prior to 1996. It is a high public health priority concern in several regions of the world. This is because the fungus is multidrug-resistant and can acquire resistance to all three major groups of current antifungal drugs (azoles, echinocandins, and amphotericin B). Outbreaks in healthcare facilities are also a concern. The main reasons for this are as follows: unlike other Candida spp. that primarily inhabit the digestive and urinary systems, C. auris readily colonizes patient skin and can survive for several weeks on dry, non-living surfaces, contributing to infections and outbreaks in healthcare facilities.In Japan, C. auris was first identified in 2009 in a discharge from the ear canal of a patient admitted to a Japanese hospital, and since then, all isolates have come from the ear canal, with only a few reported strains. For reasons unknown, as of 2022, C. auris has not been reported as a cause of invasive disease in Japan, and no nosocomial infections have occurred. Whole genome analysis suggests that all Japanese isolates belong to Clade II, affecting drug resistance and clinical characteristics.In this symposium, I will present the current status of C. auris infection in Japan, the first country where C. auris infection originated, together with its unique clinical features and molecular epidemiological analysis.

P400 A study of the ecology, evolution and resistance mechanism of Candida auris at a tertiary care center in North India

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM AimTo study the ecology, evolution, and resistance mechanism of Candida auris, using samples from patients, healthcare workers, hospital and environmental niches, using amplified fragment length polymorphism (AFLP) and antifungal susceptibility testing (AFST).MethodsA total of 720 samples were screened for C. auris, including clinical samples from patients (tissue, body fluids), surveillance samples from patients (axillar/groin swabs), swabs and water samples from environmental locations and objects, surface swabs from hospital locations, and screening samples from healthcare personnel for hand carriage of C. auris. Samples were cultured on Sabouraud Dextrose agar (SDA) and CHROMagar. Colonies morphologically suggestive of C. auris were identified by Matrix Assisted Laser Desorption-Time of Flight (MALDI-TOF) and isolates were subjected to antifungal susceptibility testing (AFST) by broth micro-dilution method. DNA was extracted for analysis by amplified fragment length polymorphism (AFLP) and cluster analysis. The amplicons were subjected to capillary electrophoresis and fluorescent amplified length polymorphism (FALP) for the generation of a heat map and dendrogram to evaluate single nucleotide polymorphisms and single nucleotide variations (SNPs and SNVs).ResultsOut of 720 samples, C. auris was isolated and identified by MALDI-TOF from 50, including 37 from routine patient samples, 12/674 axillar/groin surveillance swabs, and 1/66 samples from hands of healthcare workers. C. auris was not isolated from any environmental samples or hospital surfaces.AFST revealed high overall rates of resistance to three important antifungal drugs−93.22%, 38.98%, and 52.54% of isolates were resistant to fluconazole, voriconazole, and amphotericin B respectively. Resistance to echinocandins was lower−1.81% of isolates were resistant to caspofungin, and micafungin. Additionally, 18 isolates showed only intermediate sensitivity to both voriconazole and caspofungin.The highest rates of resistance to amphotericin B, and azoles were observed in isolates from blood (62.5% of isolates) and axillar/groin swabs (44.5% of isolates) respectively. Resistance to caspofungin was seen in 14.28% of isolates from both groups.AFLP and capillary electrophoresis of extracted DNA revealed 188 variations in the range of 300-662 nucleotides. A total of 10 samples had no change in the nucleotides and were labeled as ‘constant’. The dendrograms generated by bioinformatic analysis of FALP results yielded two different clusters provisionally designated as cluster I and cluster II. Cluster I could be further distinguished into sub-cluster Ia and sub-cluster Ib, indicating further variations.Conclusions Candida auris is a pathogen of emerging importance in our center, with significant levels of resistance to several important antifungal drugs. Incidence of both the pathogen and antifungal drug resistance was observed in samples collected from patients, but not from the hospital or environment, and minimally from healthcare personnel. This suggests that the source of most C. auris infections is colonizers from the patient rather than environmental sources or healthcare workers, and infection control measures should be tailored accordingly.