The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England.

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.

Candida auris screening practices at healthcare facilities in the United States: An Emerging Infections Network survey.

We surveyed members of the Emerging Infections Network about Candida auris screening practices at US healthcare facilities. Only 37% of respondents reported conducting screening; among these, 75% reported detection of at least 1 C. auris case in the last year. Increased screening could improve C. auris detection and prevent spread.

Navigating the Challenges of Candida auris Colonization in Rehabilitation Settings.

ABSTRACT: Candida auris is a highly transmissible yeast that is capable of causing invasive and fatal infections, particularly among persons with underlying medical conditions. Its incidence is rising, especially among patients cared for in post-acute care facilities. Individuals colonized with the yeast may be cared for in inpatient rehabilitation settings, without heightened risk for invasive infection and/or transmission to others, as long as appropriate infection control measures are followed. This article reviews key information for rehabilitation nurses caring for persons with C. auris , including risk factors for infection, the need for contact precautions, appropriate disinfection practices for therapy and diagnostic equipment, and critical components of safe transitions in the care of these patients.

Ultraviolet-C mediated inactivation of Candida auris, a rapid emerging health threat.

Health care-associated infections, particularly those caused by multidrug-resistant organisms (MDROs), pose significant challenges to patient safety. Candida auris (C auris), an emerging MDRO fungus, has been acknowledged as an urgent threat by the Centers for Disease Control and Prevention due to its high mortality and difficulty in prevention, diagnosis, and treatment. In this study, we investigated the efficacy of 254 nm ultraviolet-C light (UV-C) in inactivating C auris on hard surfaces. A mobile UV-C tower equipped with high-performance bulbs was used, and within 7 minutes of continuous exposure, ≥99.97% (≥3.86 log10) inactivation of C auris was achieved in a patient-room-sized test chamber. Our findings suggest that UV-C can serve as an adjunct infection control measure for preventing C auris and other MDRO Health care-associated infections in health care settings. Implementation of UV-C disinfection protocols can contribute to enhanced patient safety and combat the growing threat of MDRO pathogens.

Outcome of Candida auris contact investigations conducted in a 6 month period at a New York City hospital.

Candida auris is a multidrug-resistant fungus that has led to health care-associated outbreaks globally. Contact investigations for new cases of Candida auris are a recommended infection prevention practice; however, there is limited knowledge and experience with such investigations. We describe our institution's experience from June 2018 through January 2019.

Identification and infection control response to Candida auris at an academic level I trauma center.

Candida auris, an emerging fungal pathogen with significant morbidity and mortality, can be difficult for health care facilities to identify, isolate, and control. We present our identification and infection control response to Candida auris at a 695-bed academic level I trauma center in Florida.

ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model.

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP's therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 µg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 µg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

Prevalence of Acinetobacter baumannii and Candida auris in Patients Receiving Mechanical Ventilation.

Importance: To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown. Objective: To determine the prevalence of A baumannii and C auris among patients receiving mechanical ventilation in Maryland. Design, Setting, and Participants: The Maryland Multi-Drug Resistant Organism Prevention Collaborative performed a statewide cross-sectional point prevalence of patients receiving mechanical ventilation admitted to acute care hospitals (n = 33) and long-term care facilities (n = 18) between March 7, 2023, and June 8, 2023. Surveillance cultures (sputum, perianal, arm/leg, and axilla/groin) were obtained from all patients receiving mechanical ventilation. Sputum, perianal, and arm/leg cultures were tested for A baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by polymerase chain reaction for C auris. Main Outcomes and Measures: Prevalence of A baumannii, carbapenem-resistant A baumannii (CRAB), and C auris. Prevalence was stratified by type of facility. Results: All 51 eligible health care facilities (100%) participated in the survey. A total of 482 patients receiving mechanical ventilation were screened for A baumannii and 470 were screened for C auris. Among the 482 patients who had samples collected, 30.7% (148/482) grew A baumannii, 88 of the 148 (59.5%) of these A baumannii were CRAB, and C auris was identified in 31 of 470 (6.6%). Patients in long-term care facilities were more likely to be colonized with A baumannii (relative risk [RR], 7.66 [95% CI, 5.11-11.50], P < .001), CRAB (RR, 5.48 [95% CI, 3.38-8.91], P < .001), and C auris (RR, 1.97 [95% CI, 0.99-3.92], P = .05) compared with patients in acute care hospitals. Nine patients (29.0%) with cultures positive for C auris were previously unreported to the Maryland Department of Health. Conclusions: A baumannii, carbapenem-resistant A baumannii, and C auris were common among patients receiving mechanical ventilation in both acute care hospitals and long-term care facilities. Both pathogens were significantly more common in long-term care facilities than in acute care hospitals. Patients receiving mechanical ventilation in long-term care facilities are a high-risk population for emerging pathogens, and surveillance and prevention efforts should be targeted to these facilities.

Protection against lethal sepsis following immunization with Candida species varies by isolate and inversely correlates with bone marrow tissue damage.

Protection against lethal Candida albicans (Ca)/Staphylococcus aureus (Sa) intra-abdominal infection (IAI)-mediated sepsis can be achieved by a novel form of trained innate immunity (TII) involving Gr-1+ myeloid-derived suppressor cells (MDSCs) that are induced by inoculation (immunization) with low virulence Candida species [i.e., Candida dubliniensis (Cd)] that infiltrate the bone marrow (BM). In contrast, more virulent Candida species (i.e., C. albicans), even at sub-lethal inocula, fail to induce similar levels of protection. The purpose of the present study was to test the hypothesis that the level of TII-mediated protection induced by Ca strains inversely correlates with damage in the BM as a reflection of virulence. Mice were immunized by intraperitoneal inoculation with several parental and mutant strains of C. albicans deficient in virulence factors (hyphal formation and candidalysin production), followed by an intraperitoneal Ca/Sa challenge 14 d later and monitored for sepsis and mortality. Whole femur bones were collected 24 h and 13 d after immunization and assessed for BM tissue/cellular damage via ferroptosis and histology. While immunization with standard but not sub-lethal inocula of most wild-type C. albicans strains resulted in considerable mortality, protection against lethal Ca/Sa IAI challenge varied by strain was usually less than that for C. dubliniensis, with no differences observed between parental and corresponding mutants. Finally, levels of protection afforded by the Ca strains were inversely correlated with BM tissue damage (R 2 = -0.773). TII-mediated protection against lethal Ca/Sa sepsis induced by Candida strain immunization inversely correlates with BM tissue/cellular damage as a reflection of localized virulence.

ß-1,2-Oligomannan phosphorylase-mediated synthesis of potential oligosaccharide vaccine candidates.

ß-(1,2)-Mannan antigens incorporated into vaccines candidates for immunization studies, showed that antibodies raised against ß-(1,2)-mannotriose antigens can protect against disseminated candidiasis. Until recently, ß-(1,2)- mannans could only be obtained by isolation from microbial cultures, or by lengthy synthetic strategies involving protecting group manipulation. The discovery of two ß-(1,2)-mannoside phosphorylases, Teth514_1788 and Teth514_1789, allowed efficient access to these compounds. In this work, Teth514_1788 was utilised to generate ß-(1,2)-mannan antigens, tri- and tetra-saccharides, decorated with a conjugation tether at the reducing end, suitable to be incorporated on a carrier en-route to novel vaccine candidates, illustrated here by conjugation of the trisaccharide to BSA.

Efficacy of chlorhexidine in advanced performance technology formulation in decolonizing the skin using Candida auris skin colonization mouse model.

The incidence of Candida auris, an emerging multidrug resistant fungal species, is increasing. The ability of this yeast to colonize the human skin could lead to infections. Identifying agents to reduce the skin fungal burden is critical. Chlorhexidine formulated in a new Advanced Performance Technology formulation (APT-CH) was significantly more effective than untreated controls. Additional studies are warranted.

Vaccines against candidiasis: Status, challenges and emerging opportunity.

Candidiasis is a mycosis caused by opportunistic Candida species. The occurrence of fungal infections has considerably increased in the last few years primarily due to an increase in the number of immune-suppressed individuals. Alarming bloodstream infections due to Candida sp. are associated with a higher rate of morbidity and mortality, and are emerged as major healthcare concerns worldwide. Currently, chemotherapy is the sole available option for combating fungal diseases. Moreover, the emergence of resistance to these limited available anti-fungal drugs has further accentuated the concern and highlighted the need for early detection of fungal infections, identification of novel antifungal drug targets, and development of effective therapeutics and prophylactics. Thus, there is an increasing interest in developing safe and potent immune-based therapeutics to tackle fungal diseases. In this context, vaccine design and its development have a priority. Nonetheless, despite significant advances in immune and vaccine biology over time, a viable commercialized vaccine remains awaited against fungal infections. In this minireview, we enumerate various concerted efforts made till date towards the development of anti-Candida vaccines, an option with pan-fugal vaccine, vaccines in the clinical trial, challenges, and future opportunities.

The challenge of preventing and containing outbreaks of multidrug-resistant organisms and Candida auris during the coronavirus disease 2019 pandemic: report of a carbapenem-resistant Acinetobacter baumannii outbreak and a systematic review of the literature.

BACKGROUND: Despite the adoption of strict infection prevention and control measures, many hospitals have reported outbreaks of multidrug-resistant organisms (MDRO) during the Coronavirus 2019 (COVID-19) pandemic. Following an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) in our institution, we sought to systematically analyse characteristics of MDRO outbreaks in times of COVID-19, focussing on contributing factors and specific challenges in controlling these outbreaks. METHODS: We describe results of our own CRAB outbreak investigation and performed a systematic literature review for MDRO (including Candida auris) outbreaks which occurred during the COVID-19 pandemic (between December 2019 and March 2021). Search terms were related to pathogens/resistance mechanisms AND COVID-19. We summarized outbreak characteristics in a narrative synthesis and contrasted contributing factors with implemented control measures. RESULTS: The CRAB outbreak occurred in our intensive care units between September and December 2020 and comprised 10 patients (thereof seven with COVID-19) within two distinct genetic clusters (both ST2 carrying OXA-23). Both clusters presumably originated from COVID-19 patients transferred from the Balkans. Including our outbreak, we identified 17 reports, mostly caused by Candida auris (n = 6) or CRAB (n = 5), with an overall patient mortality of 35% (68/193). All outbreaks involved intensive care settings. Non-adherence to personal protective equipment (PPE) or hand hygiene (n = 11), PPE shortage (n = 8) and high antibiotic use (n = 8) were most commonly reported as contributing factors, followed by environmental contamination (n = 7), prolonged critical illness (n = 7) and lack of trained HCW (n = 7). Implemented measures mainly focussed on PPE/hand hygiene audits (n = 9), environmental cleaning/disinfection (n = 9) and enhanced patient screening (n = 8). Comparing potentially modifiable risk factors and control measures, we found the largest discrepancies in the areas of PPE shortage (risk factor in 8 studies, addressed in 2 studies) and patient overcrowding (risk factor in 5 studies, addressed in 0 studies). CONCLUSIONS: Reported MDRO outbreaks during the COVID-19 pandemic were most often caused by CRAB (including our outbreak) and C. auris. Inadequate PPE/hand hygiene adherence, PPE shortage, and high antibiotic use were the most commonly reported potentially modifiable factors contributing to the outbreaks. These findings should be considered for the prevention of MDRO outbreaks during future COVID-19 waves.

Effects of Dietary Supplementation with Green-Synthesized Zinc Oxide Nanoparticles for Candidiasis Control in Oreochromis niloticus.

Zinc is an essential element for metabolism of Nile tilapia (Oreochromis niloticus). Nanomaterials have important benefits in aquaculture. The present study evaluated the effects of green-synthesized zinc oxide nanoparticles (ZnO-NPs) using Ulva fasciata extract as an anti-fungal agent against Candida albicans (C. albicans) in vitro and in vivo in O. niloticus. A total of 252 apparent healthy O. niloticus (20 ± 0.457 g/fish) were randomly allocated into six groups: The 1st group fed on basal diet contaminated with C. albicans 15 × l06 CFU/g diet, the 2nd group fed basal diet only, the 3rd and 5th groups fed the basal diet supplemented with 40 or 60 mg/kg ZnO-NPs, respectively, and the 4th and 6th groups fed the basal diet contaminated with C. albicans 15 × l06 CFU/g and concomitantly supplemented with 40 or 60 mg/kg ZnO-NPs, respectively. The experiment lasted for 8 weeks. The phyco-synthesized ZnO-NPs were characterized by XRD, UV-V, FTIR, TEM, and zeta potential. The anti-fungal activities of ZnO-NPs and the morphological changes to C. albicans cell due to ZnO-NPs were detected. The results revealed that dietary supplementation with the green-synthesized ZnO-NPs significantly improved the growth performance, survival, serum lysozyme activity, phagocytic activity, phagocytic index, respiratory burst activity, expression of immune-related genes (IL-1ß, TGF, TNF-α), digestive enzyme activity, and histopathological finding in C. albicans-infected group, with a relative superiority to 40 mg/kg feed ZnO-NPs. It could be concluded that supplementing diets with 40 mg/kg of phyco-synthesized ZnO-NPs could be considered a better choice for controlling candidiasis in Nile tilapia.

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections.

MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.

Application of probiotics in candidiasis management.

Candidiasis (e.g., oral, gastrointestinal, vaginal, urinary tract, systemic) is a worldwide growing problem, since antifungal resistance and immunosuppression states are rising. To address this problem, very few drugs are available for the treatment of Candida spp. infections. Therefore, novel therapeutic strategies are urgently required. Probiotics have been proposed for the prevention and treatment of bacterial infections due to their safety record and efficacy, however, little is still known about their potential role regarding fungal infections. The purpose of this review is to present an updated summary of the evidence of the antifungal effects of probiotics along with a discussion of their potential use as an alternative/complementary therapy against Candida spp. infections. Thus, we performed a literature search using appropriate keywords ("Probiotic + Candida", "Candidiasis treatment", and "Probiotic + candidiasis") to retrieve relevant studies (both preclinical and clinical) with special emphasis on the works published in the last 5 years. An increasing amount of evidence has shown the potential usefulness of probiotics in the management of oral and vulvovaginal candidiasis in recent years. Among other results, we found that, as for bacterial infections, Lactobacillus, Bifidobacterium, and Saccharomyces are the most studied and effective genus for this purpose. However, in other areas, particularly in skincandidiaisis, studies are low or lacking. Thus, further investigation is necessary including in vitro and in vivo studies to establish the usefulness of probiotics in the management of candidiasis.

Trained Innate Immunity Induced by Vaccination with Low-Virulence Candida Species Mediates Protection against Several Forms of Fungal Sepsis via Ly6G+ Gr-1+ Leukocytes.

We recently discovered a novel form of trained innate immunity (TII) induced by low-virulence Candida species (i.e., Candida dubliniensis) that protects against lethal fungal/bacterial infection. Mice vaccinated by intraperitoneal (i.p.) inoculation are protected against lethal sepsis following Candida albicans/Staphylococcus aureus (Ca/Sa) intra-abdominal infection (IAI) or Ca bloodstream infection (BSI). The protection against IAI is mediated by long-lived Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs) and not by prototypical trained macrophages. This study aimed to determine if a similar TII mechanism (Gr-1+ cell-mediated suppression of sepsis) is protective against BSI and whether this TII can also be induced following intravenous (i.v.) vaccination. For this, mice were vaccinated with low-virulence Candida strains (i.p. or i.v.), followed by lethal challenge (Ca/Sa i.p. or Ca i.v.) 14 days later, and observed for sepsis (hypothermia, sepsis scoring, and serum cytokines), organ fungal burden, and mortality. Similar parameters were monitored following depletion of macrophages or Gr-1+ leukocytes during lethal challenge. The results showed that mice vaccinated i.p. or i.v. were protected against lethal Ca/Sa IAI or Ca BSI. In all cases, protection was mediated by Ly6G+ Gr-1+ putative granulocytic MDSCs (G-MDSCs), with no role for macrophages, and correlated with reduced sepsis parameters. Protection also correlated with reduced fungal burden in spleen and brain but not liver or kidney. These results suggest that Ly6G+ G-MDSC-mediated TII is induced by either the i.p. and i.v. route of inoculation and protects against IAI or BSI forms of systemic candidiasis, with survival correlating with amelioration of sepsis and reduced organ-specific fungal burden. IMPORTANCE Trained innate immunity (TII) is induced following immunization with live attenuated microbes and represents a clinically important strategy to enhance innate defenses. TII was initially demonstrated following intravenous inoculation with low-virulence Candida albicans, with protection against a subsequent lethal C. albicans intravenous bloodstream infection (BSI) mediated by monocytes with enhanced cytokine responses. We expanded this by describing a novel form of TII induced by intraperitoneal inoculation with low-virulence Candida that protects against lethal sepsis induced by polymicrobial intra-abdominal infection (IAI) via Gr-1+ leukocytes as putative myeloid-derived suppressor cells (MDSCs). In this study, we addressed these two scenarios and confirmed an exclusive role for Ly6G+ Gr-1+ leukocytes in mediating TII against either IAI or BSI via either route of inoculation, with protection associated with suppression of sepsis. These studies highlight the previously unrecognized importance of Ly6G+ MDSCs as central mediators of a novel form of TII termed trained tolerogenic immunity.

Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.