Auris Infection Research Articles

Secreted aspartyl protease 3 regulated by the Ras/cAMP/PKA pathway promotes the virulence of Candida auris.

The surge of multidrug-resistant fungal pathogens, especially Candida auris, poses significant threats to global public health. Candida auris exhibits resistance to multiple antifungal drugs, leading to major outbreaks and a high mortality rate. With an urgent call for innovative therapeutic strategies, this study focused on the regulation and pathobiological significance of secreted aspartyl proteinases (SAPs) in C. auris, as these enzymes play pivotal roles in the virulence of some fungal species. We delved into the Ras/cAMP/PKA signaling pathway's influence on SAP activity in C. auris. Our findings underscored that the Ras/cAMP/PKA pathway significantly modulates SAP activity, with PKA catalytic subunits, Tpk1 and Tpk2, playing a key role. We identified a divergence in the SAPs of C. auris compared to Candida albicans, emphasizing the variation between Candida species. Among seven identified secreted aspartyl proteases in C. auris (Sapa1 to Sapa7), Sapa3 emerged as the primary SAP in the pathogen. Deletion of Sapa3 led to a significant decline in SAP activity. Furthermore, we have established the involvement of Sapa3 in the biofilm formation of C. auris. Notably, Sapa3 was primarily regulated by Tpk1 and Tpk2. Deletion of SAPA3 significantly reduced C. auris virulence, underscoring its pivotal role in C. auris pathogenicity. The outcomes of this study provide valuable insights into potential therapeutic targets, laying the groundwork for future interventions against C. auris infection.

Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates.

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

An Overview on Candida auris in Healthcare Settings.

Candida auris has become a major concern in critical care medicine due to the increasing number of immunocompromised patients and candidiasis is the most frequent cause of fungal infections. C. auris and other fungal pathogens are responsible for at least 13 million infections and 1.5 million deaths globally per year. In immunocompromised patients, infections can quickly become severe, causing wound infections, otitis and candidemia, resulting in high morbidity and mortality. The clinical presentation of C. auris is often non-specific and similar to other types of systemic infections; in addition, it is harder to identify from cultures than other, more common types of Candida spp. Some infections are particularly difficult to treat due to multi-resistance to several antifungal agents, including fluconazole (and other azoles), amphotericin B and echinocandins. This entails treatment with more drugs and at higher doses. Even after treatment for invasive infections, patients generally remain colonized for long periods, so all infection control measures must be followed during and after treatment of the C. auris infection. Screening patients for C. auris colonization enables facilities to identify individuals with C. auris colonization and to implement infection prevention and control measures. This pathogenic fungus shows an innate resilience, enabling survival and persistence in healthcare environment and the ability to rapidly colonize the patient's skin and be easily transmitted within the healthcare setting, thus leading to a serious and prolonged outbreak.

Antifungal Use and Resistance in a Lower-Middle-Income Country: The Case of Lebanon.

Antimicrobial resistance is a serious threat, particularly in low- and middle-income countries (LMICs). Antifungal resistance is often underestimated in both healthcare and non-clinical settings. In LMICs, it is believed that the inappropriate use of antifungals, limited surveillance systems, and low diagnostic capacities are significant drivers of resistance. Like other LMICs, Lebanon lacks antifungal use and resistance surveillance programs, and the impact of antifungal resistance in the country remains unclear, especially during the unfolding economic crisis that has severely affected medical care and access to safe food and water. Interestingly, the widespread use of antifungals in medicine and agriculture has raised concerns about the development of antifungal resistance in Lebanon. In this light, we aimed to survey available antifungal drugs in the country and evaluate susceptibility patterns of prevalent fungal species to guide empiric treatments and develop antifungal stewardship programs in Lebanon. We noted that the economic crisis resulted in significant increases in antifungal drug prices. Additionally, a comprehensive literature search across PubMed, ScienceDirect, and Google Scholar databases identified 15 studies on fungal infections and antifungal resistance conducted from 1998 to 2023 in Lebanon. While data on antifungal resistance are limited, 87% of available studies in Lebanon focused on candidiasis, while the remaining 13% were on aspergillosis. Overall, we observed a marked antimicrobial resistance among Candida and Aspergillus species. Additionally, incidences of Candida auris infections have increased in Lebanese hospitals during the COVID-19 pandemic, with a uniform resistance to fluconazole and amphotericin-B. Taken together, a One Health approach, reliable diagnostics, and prudent antifungal use are required to control the spread of resistant fungal pathogens in healthcare and agricultural settings.

An Observational Study of Candida auris Infections with Special Reference to the Clinicomicrobiological Problems Faced in Day-to-Day Practice at a Tertiary Care Hospital in Eastern India

An Observational Study of Candida auris Infections with Special Reference to the Clinicomicrobiological Problems Faced in Day-to-Day Practice at a Tertiary Care Hospital in Eastern India

Molecular Detection of Candida auris Using DiaSorin Molecular Simplexa® Detection Kit: A Diagnostic Performance Evaluation.

Candida auris is a globally emerging fungal pathogen that is associated with healthcare-related infections. The accurate and rapid detection of C. auris is crucial for effective infection prevention, control, and patient management. This study aimed to validate the analytical and diagnostic performance of the DiaSorin Molecular C. auris Detection Kit. The analytical specificity, sensitivity, and reproducibility of the assay were evaluated. The limit of detection (LOD) was determined to be 266 CFU/µL using the ZeptoMetrix Candida auris Z485 strain and standard calibration curves. The assay demonstrated high analytical specificity and showed no amplification against a diverse panel of bacteria and fungi. Clinical validation was conducted using deidentified residual axillary/groin surveillance culture specimens from C. auris culture-positive and culture-negative patients. The DiaSorin Molecular Detection Kit exhibited 100% agreement in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) when compared to cultures coupled with MALDI-TOF identification. Intra- and inter-reproducibility testing demonstrated consistent and reliable diagnostic performance. This validated assay offers rapid and accurate detection of C. auris, facilitating timely implementation of infection control measures and appropriate patient care. The DiaSorin Molecular C. auris Detection Kit has the potential to aid in controlling the outbreaks caused by this emerging fungal pathogen. Providing a reliable diagnostic tool can contribute to the effective management and containment of C. auris infections in healthcare settings and ultimately improve patient outcomes.

Saquinavir potentiates itraconazole's antifungal activity against multidrug-resistant Candida auris in vitro and in vivo.

Candida species are highly opportunistic yeasts that are responsible for serious invasive fungal infections among immunocompromised patients worldwide. Due to the increase of drug resistance and incidence of infections, there is an urgent need to develop new antifungals and to identify co-drugs that can sensitize drug-resistant Candida to antifungals. The objective of this study was to assess the effect of saquinavir on the activity of azole antifungals against Candida auris. The in vitro interaction of saquinavir and three azole antifungals (itraconazole, voriconazole and fluconazole) was evaluated against a panel of C. auris isolates. The itraconazole/saquinavir combination exhibited a synergistic relationship against all C. auris isolates tested with the fractional inhibitory concentration index (FICI) ranging from 0.03 to 0.27. Moreover, a time-kill kinetics assay revealed that saquinavir restored the itraconazole's fungistatic activity against C. auris. Furthermore, saquinavir restored itraconazole's antifungal activity against other clinically important Candida species. The mechanistic investigation indicated that saquinavir significantly inhibited efflux pumps, glucose utilization and ATP synthesis in Candida. Finally, a murine model of C. auris infection was used to evaluate the efficacy of the itraconazole/saquinavir combination in the presence of ritonavir (as a pharmacokinetic enhancer). The combination significantly reduced the fungal burden in the kidneys by 0.93-log10 colony forming units (88%) compared to itraconazole alone. This study identified that saquinavir exhibits a potent synergistic relationship in combination with itraconazole against Candida species, which warrants further consideration.

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.

COVID-19-associated candidiasis and the emerging concern of Candida auris infections.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

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.

Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Candida auris: a growing threat to global health

Candida auris (C. auris) belongs to the Candida genus and is a fungal yeast resistant to multiple drugs. It is highly virulent and evades current therapeutic remedies. It was first discovered in a Japanese hospital in 2009 from a patient’s external auditory canal1. C. auris infection has a high worldwide mortality, which ranges from 30% to 60%, and is frequently associated with bloodstream infections2. The rapid spread of C. auris infection occurred after 2009. The Centers for Disease Control and Prevention (CDC) has estimated the presence of C. auris isolates in 41 countries, typically in hospital settings, as of March 20203. CDC also reported outbreaks of infections with C. auris in 47 countries globally on February 15, 20214. The United States reported 2377 clinical cases and 5754 screening cases from January 2022 to December 20225. Twenty-six isolates of C. auris from India were different genetically and phenotypically from the ones found in Japan and Korea, which provided evidence for C. auris’s ability to mutate and its resistance to Azoles6. The mechanism of C. auris virulence factors is relatively unknown. According to genomic comparison, C. auris has the ability to adapt to different environments. Two mechanisms of its pathogenesis have been identified, which include hydrolytic enzyme production and attack host cells and tissues. It can also form biofilms that protect it from antifungal drugs and increase its ability in nosocomial transmission4. C. auris can be spread in health care facilities such as hospitals and nursing homes through direct patient-to-patient contact. Contaminated surfaces are a significant culprit in the spread when a person comes in contact with them. As C. auris colonizes the skin and can be transmitted into the environment, both properties make it easily transmissible. Population susceptible are immunocompromised people, recently hospitalized patients in areas where C. auris is endemic; catheter use, extended stay in ICU, previous history of antimicrobial exposure, and resistance to antifungal therapy7. Identifying this pathogen is tricky as the methods used to determine the yeast in laboratories often must be corrected for other fungi. Detection of C. auris requires reliable sampling procedures from the most common sites of colonization, including the axillae and groin. Nares, external auditory canals, urine, rectum, catheter sites, and vagina also serve as colonization sites8. Making use of water and soaps or using a hand sanitizer with a 60% alcohol content is effective in preventing infection. Health care workers should take proper precautions to use gowns and gloves in the hospital setting. Regular disinfection and cleaning of surfaces prevent the survival of C. auris. When referring a patient with C. auris, the health care facility on the receiving end should be informed of the patient’s infection or colonization status to take appropriate measures promptly9. The steadily rising incidence of C. auris outbreaks poses a significant public health threat. C. auris outbreaks are a challenge to control due to poor routine diagnostic detection, prompt transmission, and resistance to disinfection techniques. It is now a leading cause of fungal infections in many medical setups with high mortality rates. Rapid detection methods that provide reliable identification and diagnosis, as well as control measures and necessary precautions, will help contain the spread of C. auris in health care systems. Ethical approval None. Consent for publication None. Sources of funding None. Author contributions The conceptualization was done by H.F. and H.S.R. The literature and drafting of the manuscript were conducted by H.F., A.M.S., F.R., and B.S.R. The editing and supervision were performed by H.S.R. All authors have read and agreed to the final version of the manuscript. Conflict of interest disclosures The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor All authors take responsibility for the work, access to data and decision to publish. Provenancer and Peer review Not commissioned, externally peer reviewed.

Risk factors and mortality of the newly emerging Candida auris in a university hospital in Saudi Arabia

ABSTRACT Candida auris presents a global health threat. We investigated risk factors and mortality of Candida auris infections in a retrospective study in Saudi Arabia. We included 27 patients ≥14 with invasive Candida auris from 2015–2022, with median age 58, and 66.7% males. All patients had indwelling devices. The most common infection sources were central line-associated bloodstream infection in 17 (63.0%), and urinary tract infections in four (12%). Fever and shock were observed in nine patients (33.3%) each, and 22 (81%) were admitted to the intensive care unit. Common comorbidities were diabetes and heart disease in 13 (48.1%) patients each. The median hospital stay was 78 days, and the median Charlson index was 4. The C. auris cultures were 100% susceptible to voriconazole, caspofungin, and amphotericin, while three were fully susceptible to fluconazole (11.1%). Despite treatment, 18 (66.7%) patients died. In conclusion, invasive C. auris infection had varied presentations. All patients had indwelling devices, and many had lengthy hospital stays. All isolates were susceptible to amphotericin and echinocandins, while few were fully susceptible to fluconazole.

Lopinavir and ritonavir act synergistically with azoles against Candida auris in vitro and in a mouse model of disseminated candidiasis

The emergence of Candida auris has created a global health challenge. Azole antifungals are the most affected antifungal class because of the extraordinary capability of C. auris to develop resistance against these drugs. Here, we used a combinatorial therapeutic approach to sensitize C. auris to azole antifungals. We have demonstrated the capability of the HIV protease inhibitors lopinavir and ritonavir, at clinically relevant concentrations, to be used with azole antifungals to treat C. auris infections both in vitro and in vivo. Both lopinavir and ritonavir exhibited potent synergistic interactions with the azole antifungals, particularly with itraconazole against 24/24 (100%) and 31/34 (91%) of tested C. auris isolates, respectively. Furthermore, ritonavir significantly interfered with the fungal efflux pump, resulting in a significant increase in Nile red fluorescence by 44%. In a mouse model of C. auris systemic infection, ritonavir boosted the activity of lopinavir to work synergistically with fluconazole and itraconazole and significantly reduced the kidney fungal burden by a 1.2 log (∼94%) and 1.6 log (∼97%) CFU, respectively. Our results urge further comprehensive assessment of azoles and HIV protease inhibitors as a novel drug regimen for the treatment of serious invasive C. auris infections.

Nanoemulsion Increases the Antifungal Activity of Amphotericin B against Four Candida auris Clades: In Vitro and In Vivo Assays.

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.

Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris.

Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed.

Azole resistance in Candida auris: mechanisms and combinatorial therapy.

Multidrug resistance Candida auris is a dangerous fungal pathogen that is emerging at an alarming rate and posing serious threats to public health. C. auris is associated with nosocomial infections that cause invasive candidiasis in immunocompromised patients. Several antifungal drugs with distinct mechanisms of action are clinically approved for the treatment of fungal infections. The high rates of intrinsic and acquired drug resistance, particularly to azoles, reported in characterized clinical isolates of C. auris make treatment extremely problematic. In systemic infections, azoles are the first-line treatment for most Candida species; however, the increasing use of drugs results in the frequent emergence of drug resistance. More than 90% of the clinical isolates of C. auris is shown to be highly resistant to azole drugs especially fluconazole, with some strains (types) resistant to all three classes of commonly used antifungals. This presents a huge challenge for researchers in terms of completely understanding the molecular mechanism of azole resistance to develop more efficient drugs. Due to the scarcity of C. auris therapeutic alternatives, the development of successful drug combinations provides an alternative for clinical therapy. Taking advantage of various action mechanisms, such drugs in combination with azole are likely to have synergistic effects, improving treatment efficacy and overcoming C. auris azole drug resistance. In this review, we outline the current state of understanding about the mechanisms of azole resistance mainly fluconazole, and the current advancement in therapeutic approaches such as drug combinations toward C. auris infections.

Investigation of the first cluster of Candida auris cases among pediatric patients in the United States―Nevada, May 2022

Background:Candida auris is a frequently drug-resistant yeast that can cause invasive disease and is easily transmitted in healthcare settings. Pediatric cases are rare in the United States, with &lt;10 reported before 2022. In August 2021, the first C. auris case in Las Vegas was identified in an adult. By May 2022, 117 cases were identified across 16 healthcare facilities, including 3 pediatric cases at an acute-care hospital (ACH) with adult cases, representing the first pediatric cluster in the United States. The CDC and Nevada Division of Public and Behavioral Health (NVDPBH) sought to describe these cases and risk factors for C. auris acquisition. Methods: We defined a case as a patient’s first positive C. auris specimen. We reviewed medical records and infection prevention and control (IPC) practices. Environmental sampling was conducted on high-touch surfaces throughout affected adult and pediatric units. Isolate relatedness was assessed using whole-genome sequencing (WGS). Results: All 3 pediatric patients were born at the facility and had congenital heart defects. All were aged &lt;6 months when they developed C. auris bloodstream infections; 2 developed C. auris endocarditis. One patient died. Patients overlapped in the pediatric cardiac intensive care unit; 2 did not leave between birth and C. auris infection. Mobile medical equipment was shared between adult and pediatric patients; lapses in cleaning and disinfection of shared mobile medical equipment and environmental surfaces were observed, presenting opportunities for transmission. Overall, 32 environmental samples were collected, and C. auris was isolated from 2 specimens from an adult unit without current cases. One was a composite sample from an adult patient’s bed handles, railings, tray table and call buttons, and the second was from an adult lift-assistance device. WGS of specimens from adult and pediatric cases and environmental isolates were in the same genetic cluster, with 2–10 single-nucleotide polymorphisms (SNPs) different, supporting within-hospital transmission. The pediatric cases varied by 0–3 SNPs; at least 2 were highly related. Conclusions:C. auris was likely introduced to the pediatric population from adults via inadequately cleaned and disinfected mobile medical equipment. We made recommendations to ensure adequate cleaning and disinfection and implement monitoring and audits. No pediatric cases have been identified since. This investigation demonstrates transmission can occur between unrelated units and populations and that robust infection prevention and control practices throughout the facility are critical for reducing C. auris environmental burden and limiting transmission, including to previously unaffected vulnerable populations, like children.Disclosures: None

Alarming prevalence of Candida auris among critically ill patients in intensive care units in Dhaka City, Bangladesh

Background:Candida auris is a multidrug-resistant yeast capable of invasive infection with high mortality and healthcare-associated outbreaks globally. Due to limited labratory capacity, the burden of C. auris is unknown in Bangladesh. We estimated the extent of C. auris colonization and infection among patients in Dhaka city intensive care units. Methods: During August 2021–September 2022 at adult intensive care units (ICUs) and neonatal intensive care units (NICUs) of 1 government and 1 private tertiary-care hospital, we collected skin swabs from all patients and blood samples from sepsis patients on admission, mid-way through, and at the end of ICU or NICU stays. Skin swab and blood with growth in blood-culture bottle were inoculated in CHROMagar, and identification of isolates was confirmed by VITEK-2. Patient characteristics and healthcare history were collected. We performed descriptive analyses, stratifying by specimen and ICU type. Results: Of 740 patients enrolled, 59 (8%) were colonized with C. auris, of whom 2 (0.3%) later developed a bloodstream infection (BSI). Among patients colonized with C. auris, 27 (46%) were identified in the ICU and 32 (54%) were identified from the NICU. The median age was 55 years for C. auris–positive ICU patients and 4 days for those in the NICU. Also, 60% of all C. auris patients were male. Among 366 ICU patients, 15 (4%) were positive on admission and 12 (3%) became colonized during their ICU stay. Among 374 NICU patients, 19 (5%) were colonized on admission and 13 (4%) became colonized during their NICU stay. All units identified C. auris patients on admission and those who acquired it during their ICU or NICU stay, but some differences were observed among hospitals and ICUs (Figure). Among patients colonized on admission to the ICU, 11 (73%) were admitted from another ward, 3 (20%) were admitted from another hospital, and 1 (7%) were admitted from home. Of patients colonized on admission to the NICU, 4 (21%) were admitted from the obstetric ward, 9 (47%) were admitted from another hospital, and 6 (32%) were admitted from home. In addition, 18 patients with C. auris died (12 in the ICU and 6 in the NICU); both patients with C. auris BSIs died. Conclusions: In these Bangladesh hospitals, 8% of ICU or NICU patients were positive for C. auris, including on admission and acquired during their ICU or NICU stay. This high C. auris prevalence emphasizes the need to enhance case detection and strengthen infection prevention and control. Factors contributing to C. auris colonization should be investigated to inform and strengthen prevention and control strategies.Disclosure: None

Synergistic Antifungal Interaction between Pseudomonas aeruginosa LV Strain Metabolites and Biogenic Silver Nanoparticles against Candida auris.

Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fungal cells. F4a and indolin-3-one combined with bioAgNP exhibited synergistic fungicidal activity against planktonic cells. F4a, alone or combined with bioAgNP, also caused a significant decrease in the number of viable cells within the biofilms. No cytotoxicity to mammalian cells was detected for bacterial metabolites combined with bioAgNP at synergistic concentrations that presented antifungal activity. These results indicate the potential of F4a combined with bioAgNP as a new strategy for controlling C. auris infections.