Persistent Candidemia Research Articles

Congenital Sepsis with Candida albicans-A Rare Event in the Neonatal Period: Report of Two Cases and Literature Review.

Candida spp. is rarely found in neonatal early-onset sepsis (EOS) etiology. However, candidemia is associated with increased mortality and morbidity, as in late-onset sepsis. Congenital candidiasis may present as a mucocutaneous infection or, more rarely, as a systemic infection in term and preterm infants. This paper presents case reports of two cases of congenital systemic candidiasis (CSC) caused by Candida albicans and a review of the data in the literature. An electronic search of PubMed, Scopus, and Google Scholar was performed to identify publications on congenital candidiasis. Both neonates were male, born vaginally, with risk factors for congenital candidiasis. One of the infants was born at term and presented with an almost generalized maculopapular rash at birth and congenital candidemia; parenteral fluconazole was used successfully. The other infant was born prematurely at 28 weeks of gestation; blood culture, gastric aspirate, and maternal vaginal cultures sampled at birth were positive for C. albicans. Liver and kidney involvement became apparent on the third day of life, while lung involvement was clinically evident on the fourth day. Prolonged parenteral fluconazole was administered due to multiple organ involvement and persistent candidemia. Our experience with the presented cases, similar to data in the literature, suggests that CSC may occur at any gestational age, with various clinical pictures, sometimes mimicking bacterial sepsis, and even in the absence of the rash. Careful anamnesis and a high index of suspicion are important for the prompt recognition and treatment of CSC, optimizing the short- and long-term outcomes. Further research should focus on CSC to improve its diagnosis.

Integrating omics techniques and culture-independent systems may improve the detection of persistent candidemia: data from an observational study

IntroductionBlood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2.MethodsThis is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample.Results10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00–1.00) when candidemia was defined according to both methods.ConclusionIntegrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole

ObjectivesThe trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy. MethodsWe retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1–5%), slight (6–10%), moderate (11–15%), and heavy trailers (>15%). ResultsAmong isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38–26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01–1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27–79.88, p = 0.029) were independent factors for persistent candidemia. DiscussionThe current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment.

P10 The yeast of our worries: a challenging case of persistent candidaemia following emergency abdominal surgery

Abstract Case summary A 47-year-old woman with a past medical history of osteoarthritis only presented to hospital with abdominal pain three days following a diagnostic colonoscopy performed for suspected bowel malignancy. Upon admission, she was diagnosed with a bowel perforation and subsequently underwent an emergency laparotomy and anterior resection for a newly diagnosed sigmoid adenocarcinoma. Her recovery was complicated by an anastomotic leak requiring multiple washouts due to faeculent peritoneal soiling. Following surgery, she was admitted to the ICU with an open abdomen for vacuum-assisted wound closure and mesh-mediated fascial traction. A sample of peritoneal fluid taken during her initial washout grew Escherichia coli, for which she was initially treated with piperacillin/tazobactam, and later, meropenem, after another E. coli isolate from a sample of intra-abdominal pus collected during a subsequent washout demonstrated piperacillin/tazobactam resistance. Despite treatment with meropenem, the patient continued to have intermittent fevers up to 40°C. Blood cultures taken during a febrile episode grew yeasts identified as Candida glabrata, at which point anidulafungin was commenced empirically. Computed tomography imaging of the chest, abdomen and pelvis did not reveal any potential source of invasive candidiasis. To exclude line infection as the source of the Candida, all central lines were removed, leaving only peripheral venous access. Despite this, the candidaemia continued. In total, 18 blood cultures taken over a period of 19 days grew C. glabrata. After 7 days of empirical treatment with anidulafungin, voriconazole was added in view of the persistent elevation in the patient’s serum β-D-glucan (BDG) and recurrent isolation of C. glabrata from blood cultures. Flucytosine was added after a further 10 days with no effect on the patient’s clinical status. Following removal of the abdominal mesh and the eventual closure of the patient’s abdomen, the time to positivity for her blood cultures gradually increased and eventually became negative at 5 days. Flucytosine was then stopped and anidulafungin and voriconazole were continued. A sustained decline in the patient’s serum BDG was observed thereafter and antifungal treatment was eventually stopped after three negative BDG measurements were obtained.1 Conclusions Fungal mesh infection is a rare but serious complication of abdominal surgery involving mesh insertion.2 To our knowledge, this is the first reported case of abdominal surgical mesh infection caused by C. glabrata. Previously reported cases in the literature have been due to other Candida spp. (albicans, krusei and norvegensis), Aspergillus and Coccidioides spp.1–3 C. glabrata is particularly adept at biofilm formation, causing low therapeutic response to antifungal treatment.4 In this case, source control could not be readily achieved as the mesh was required to aid abdominal closure, resulting in treatment failure despite triple antifungal therapy. This case serves as a stark reminder of the devastating and potentially fatal consequences that may result from this surgical complication and the perils associated with the use of mesh in abdominal surgery when the peritoneum has been soiled.

Disseminated Disease After Candidemia in Children and Young Adults: Epidemiology, Diagnostic Evaluation and Risk Factors.

Treatment of candidemia may be complicated by hematogenous dissemination. Limited data exist to guide decision-making regarding the evaluation for disseminated disease. We sought to describe the epidemiology of invasive disease after candidemia, report the diagnostic evaluations performed and identify risk factors for disseminated disease. We performed a retrospective single-center study of candidemia from January 1, 2012 to December 31, 2022. Disseminated candidiasis was defined as radiologic findings consistent with end-organ disease, abnormal ophthalmologic exam or growth of Candida spp. from a sterile site after an episode of candidemia. A multilevel regression model was used to identify risk factors for dissemination. The cohort included 124 patients with 144 episodes of candidemia. Twelve patients died before an evaluation for dissemination occurred. Only 107/132 patients underwent evaluation for dissemination. Tests obtained included abdominal imaging (93/132), echocardiography (91/132), neuroimaging (45/132) and chest imaging (38/132). A retinal examination was performed in 90/132 patients. Overall, 27/107 patients (25%) had disseminated disease. Frequently identified sites of dissemination were lungs and abdominal organs. Regression modeling identified prematurity [adjusted odds ratio (aOR): 11.88; 95% confidence interval (CI): 1.72-81.90] and mitochondrial and genetic disease (aOR: 5.66; 95% CI: 1.06-30.17) as risk factors for disseminated candidiasis. Each additional day of candidemia increased the odds of dissemination (aOR: 1.36; 95% CI: 1.12-1.66). In a heterogeneous cohort of patients, disseminated candidiasis was common. Evaluation for disseminated disease was variable. Those with persistent candidemia had significantly increased risk of dissemination and should undergo a standardized evaluation for disseminated disease.

2447. Clinical Features and Outcome of Persistent Candidemia Caused by Candida albicans versus Non-albicans Candida Species: A Focus on Antifungal Resistance and Follow-up Blood Cultures

Abstract Background Candidemia is a common hospital-acquired (HA) infection linked to extended hospitalization and high mortality rates. Risk factors for persistent candidemia (PC) include central venous catheter, empirical treatment, and metastatic infection foci. Antifungal resistance is a significant global infection control issue, especially in non-albicans Candida species. We investigated clinical outcomes and mortality rates associated with HA-PC, focusing on Candida species, antifungal resistance, and PC-clearance. Methods Data analysis was conducted using electronic medical records from Tohoku University Hospital from 2012 to 2021 (n = 60). HA-PC cases were categorized based on Candida species, azole or echinocandin resistance, and PC-clearance status, and analyzed respective characteristics. The primary outcome variables were 30-day, 30–90-day, and 90-day mortality after the initial blood culture. Results The HA-persistent non-albicans candidemia group had a higher ratio of immunosuppression and catheter-related bloodstream infection (CRBSI) than the HA-persistent Candida albicans bacteremia group (Odds ratio [OR] = 4.6, p = 0.049). CRBSI was more prevalent in the HA-PC resistant strain group than in the susceptible strain group (OR = 4.2, p = 0.008), while HA-PC resistant strain group had a lower incidence of intraocular candidiasis (p = 0.020). Mortality rates were slightly higher in the HA-persistent non-albicans candidemia group compared to the HA-persistent Candida albicans bacteremia group. Similarly, the HA-PC resistant strain group tended to have higher mortality rates compared to the susceptible strain group. In the HA-PC non-clearance group, there was a trend towards higher 30-day, and 90-day mortality rates, and the former group had a statistically significant difference (OR = 19, p = 0.028). Conclusion Patients with HA-PC caused by non-albicans Candida or azole or echinocandin resistant strains have higher mortality rates and require careful therapeutic management. Confirming the clearance of PC by performing follow-up blood cultures can improve the survival rate for both susceptive and resistant strain groups. Disclosures Shiori Kitaya, MD, AMANO Co., Ltd.: Grant/Research Support Hajime Kanamori, MD, PhD, MPH, Amano Co., Ltd.: Grant/Research Support Koichi Tokuda, MD, PhD, MPH, AMANO Co., Ltd.: Grant/Research Support

Breakthrough candidemia with hematological disease: Results from a single-center retrospective study in Japan, 2009-2020.

Breakthrough candidemia (BrC) is a significant problem in immunocompromised patients, particularly those with hematological disorders. To assess the characteristics of BrC in patients with hematologic disease treated with novel antifungal agents, we collected clinical and microbiological information on said patients from 2009 to 2020 in our institution. Forty cases were identified, of which 29 (72.5%) received hematopoietic stem cell transplant (HSCT)-related therapy. At BrC onset, the most administered class of antifungal agents were echinocandins, administered to 70% of patients. Candida guilliermondii complex was the most frequently isolated species (32.5%), followed by C. parapsilosis (30%). These two isolates were echinocandin-susceptible in vitro but had naturally occurring FKS gene polymorphisms that reduced echinocandin susceptibility. Frequent isolation of these echinocandin-reduced-susceptible strains in BrC may be associated with the widespread use of echinocandins. In this study, the 30-day crude mortality rate in the group receiving HSCT-related therapy was significantly higher than in the group not receiving it (55.2% versus 18.2%, P=.0297). Most patients affected by C. guilliermondii complex BrC (92.3%) received HSCT-related therapy and had a 30-day mortality rate of 53.8%; despite treatment administration, 3 of 13 patients had persistent candidemia. Based on our results, C. guilliermondii complex BrC is a potentially fatal condition in patients receiving HSCT-related therapy with echinocandin administration.

Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility Testing and Antifungal Therapy.

To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness. A literature search using the PubMed database (inception to March 2023) was conducted using the search terms "invasive candidiasis," "candidemia," "critically ill," "azoles," "echinocandin," "antifungal agents," "rapid diagnostics," "antifungal susceptibility testing," "therapeutic drug monitoring," "antifungal dosing," "persistent candidemia," and "Candida biofilm." Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov. A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated. Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia. Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.

Epidemiology, antifungal susceptibility, risk factors, and mortality of persistent candidemia in adult patients in China: a 6-year multicenter retrospective study

BackgroundData on persistent candidemia (PC), a recognized complication of candidemia, are lacking in China. This study aimed to investigate the clinical characteristics and risk factors for the mortality of PC among adults in China.MethodsThis 6-year retrospective study analyzed the prevalence, species distribution, antifungal susceptibility, risk factors, and patient mortality of PC among adults in three regional tertiary teaching hospitals in China from 2016 to 2021. We collected electronic laboratory records data of PC and non-PC patients and used the Student test or Mann–Whitney U test for a retrospective study. Logistic regression was used to identify risk factors associated with persistent candidemia.ResultsThe definition of PC was fulfilled by 36 patients (13.7%, 36/263). The mean age of the patients was 59.9 years (60 years for patients with PC; 59.8 years for those with non-PC; P > 0.05) and 131 (60.1%) were men [16 with PC (44.4%), 115 with non-PC (63.2%), P < 0.05]. The mean annual incidence was 0.15/1000 admissions (including PC 0.03/1000 admissions vs. non-PC 0.12/1000 admissions, P < 0.05). Candida parapsilosis (14/36, 38.9%) and Candida albicans (81/182, 44.5%) were the predominant pathogens in patients with PC and non-PC, respectively. Most isolates were susceptible to flucytosine (99.0%) and amphotericin B (99.5%), and the activity of antifungal agents against Candida species was not statistically significantly different between patients with PC and non-PC (P > 0.05). The 30-day mortality rate was 20.2% (16.7% with PC vs. 20.9% with non-PC, P > 0.05). Multivariable regression analysis showed that use of broad-spectrum antibiotics (odds ratio (OR), 5.925; 95% confidence interval (CI), 1.886–18.616, P = 0.002), fluconazole (OR, 3.389; 95% CI, 1.302–8.820, P = 0.012) and C. parapsilosis infection (OR, 6.143; 95% CI, 2.093–18.031, P = 0.001) were independent predictors of PC, sex (male) (OR, 0.199; 95% CI, 0.077–0.518, P = 0.001) was the protective factor for PC. Respiratory dysfunction (OR, 5.763; 95% CI, 1.592–20.864, P = 0.008) and length of hospital stay(OR, 0.925; 95% CI, 0.880–0.973, P = 0.002) were independent predictors of 30-day mortality in patients with non-PC. C. tropicalis bloodstream infection (OR, 12.642; 95% CI, 1.059–150.951; P = 0.045) was an independent predictor of 30-day mortality in patients with PC.ConclusionsThe epidemiological data of patients with PC and non-PC were different in the distribution of Candida species, the mean annual incidence and independent predictors of 30-day mortality. Flucytosine and amphotericin B could be used as first-choice drugs in the presence of PC infections.

Clinical Features and Outcomes of Persistent Candidemia Caused by Candida albicans versus Non-albicans Candida Species: A Focus on Antifungal Resistance and Follow-Up Blood Cultures.

The clinical distinctions among variations in Candida species, antifungal resistance (AFR), and clearance status of hospital-acquired persistent candidemia (HA-PC) remain uncertain. This secondary analysis of a retrospective cohort study aimed to assess the differences in HA-PC based on different Candida species, AFR, and persistent candidemia (PC) clearance status. A retrospective review was conducted using medical records from Tohoku University Hospital of patients for whom blood cultures were performed between January 2012 and December 2021. PC cases were categorized into groups based on Candida species, azole, or echinocandin resistance, as well as PC-clearance status, and the respective characteristics were analyzed. The HA-PC non-clearance group had a tendency toward higher 30-90-day and 90-day mortality rates compared to the HA-PC-clearance group in both the susceptible and resistant strain groups, with the former group demonstrating a statistically significant difference (odds ratio = 19, p = 0.028). The high mortality rate observed in the Candida non-albicans and resistant strain groups necessitates a more meticulous therapeutic management approach for PC. Follow-up blood cultures and confirmation of PC clearance are useful for improving the survival rates of both the HA-PC-susceptible and -resistant strain groups.

Candida auris as an Emergent Public Health Problem: A Current Update on European Outbreaks and Cases.

Candida auris is considered to be an emerging fungal pathogen and is related to high mortality rates, persistent candidemia, inconsistencies in susceptibility testing results and misidentification by available commercial identification systems. Multidrug-resistant (MDR) and pandrug-resistant (PDR) strains are increasingly detected. In Europe, hospital outbreaks caused by C. auris have been reported in the United Kingdom (UK), Italy and Spain; however, several cases have been sporadically detected in all European countries. C. auris is difficult to control despite enhanced control measures due to its ability to survive for a long time in environments and colonize patients for prolonged periods. An adequate laboratory diagnostic capacity and national surveillance are fundamental to rapidly detect new C. auris cases and to apply the correct measures to circumscribe them and prevent their spread. Our narrative review aims to highlight the primary C. auris outbreaks and case reports that have occurred in Europe.

SG-APSIC1031: Reappraisal of the effectiveness of a care bundle for patients with candidemia

Objectives: Candidemia has become one of the leading causes of healthcare-associated bloodstream infection, particularly in the intensive care unit. The management of candidemia remains challenging. We reassessed the protective effectiveness of a comprehensive care bundle on the management of candidemia and the effects of compliance with each element on the outcomes of patients. Methods: This network meta-analysis was conducted using the frequentist method. The participants included adult patients both infected with candidemia and who received bundle care. The primary outcome was the all-cause mortality among the patients included. Results: Studies in which a care bundle was created for patients with candidemia were identified, and 5 eligible studies with 5,808 participants were enrolled for further analysis. The random-effects model of the overall odds ratio (OR) revealed a significant reduction in the risk of all-cause mortality compared with that of the controls (OR, 0.599; 95% CI, 0.378–0.949; P = .025), as well as a reduction in the risk of developing persistent candidemia compared with the controls (OR, 0.483; 95% CI, 0.245–0.952; P = .008). In addition, no single element reached a protective effectiveness to improve the clinical outcome. Conclusions: This meta-analysis demonstrated that the combination of core elements in the care bundle resulted in protective effects, in that the all-cause mortality rates and incidence rates were effectively reduced among patients with persistent candidemia.

A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols.

Fluconazole (FLC) is widely used to prevent and treat invasive fungal infections. However, FLC is a fungistatic agent, allowing clinical FLC-susceptible isolates to tolerate FLC. Making FLC fungicidal in combination with adjuvants is a promising strategy to avoid FLC resistance and eliminate the persistence and recurrence of fungal infections. Here, we identify a new small molecule compound, CZ66, that can make FLC fungicidal. The mechanism of action of CZ66 is targeting the C-4 sterol methyl oxidase, encoded by the ERG251 gene, resulting in decreased content of sterols with the 14α-methyl group and ultimately eliminating FLC tolerance of Candida albicans. CZ66 most likely interacts with Erg251 through residues Glu195, Gly206, and Arg241. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14α-methylsterol synthesis and open the way to abolishing fungal FLC tolerance. IMPORTANCE Fluconazole (FLC) tolerance increases the frequency of acquired FLC resistance, and a high FLC tolerance level is associated with persistent candidemia. Multiple functional proteins, such as calcineurin, heat shock protein 90 (Hsp90), and ADP ribosylation factor, are essential for the survival of C. albicans exposed to FLC, but how these factors increase the fungicidal activity of FLC remains to be determined. In this study, we found that 14α-methylsterols replace ergosterol to allow C. albicans to survive FLC, but Erg251 inactivated by CZ66 results in loss of 14α-methylsterol synthesis and cell death of C. albicans treated with FLC. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14α-methylsterol synthesis and open the way to abolishing fungal FLC tolerance.

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.

Clinical and Microbiological Characteristics of Neonates with Candidemia and Impacts of Therapeutic Strategies on the Outcomes.

Neonatal candidemia is associated with significant morbidities and a high mortality rate. We aimed to investigate the clinical characteristics of Candida bloodstream infections in neonates and the impact of therapeutic strategies on the outcomes. We identified all the neonates with candidemia from a medical center in Taiwan over an 18-year period (2003–2021) and analyzed them. Clinical isolates were confirmed by DNA sequencing, and antifungal susceptibility testing was performed. The prognostic factors associated with clinical treatment failure (30-day, all-cause mortality and persistent candidemia > 72 h after antifungal agents) and in-hospital mortality were analyzed using logistic regression modeling. A total of 123 neonates with 139 episodes of candidemia were included in the study. The median (IQR) gestational age and birth weight of the neonates with candidemia were 29.0 (26.0–35.0) weeks and 1104.0 (762.0–2055) g, respectively. The most common Candida spp. was Candida albicans (n = 57, 41.0%), followed by C. parapsilosis (n = 44, 31.7%), Candida guilliermondii (n = 12, 8.6%), and C. glabrata (n = 11, 7.9%). The overall susceptibility to fluconazole was 81.3%, and the resistant rates against other antifungal agents were less than 3%. The cumulative mortality rate at 7 and 30 days after the first episode of candidemia was 11.3% and 32.3%, respectively. The overall in-hospital mortality rate was 42.3%. The treatment outcomes did not change over the study period and were not affected by delayed initiation of antifungal agents. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.54; 95% confidence interval [CI]: 1.93–15.86, p = 0.001), septic shock (OR, 7.88; 95% CI: 2.83–21.93, p < 0.001), and multiple chronic comorbidities (OR, 8.71; 95% CI: 1.82–41.81, p = 0.007) were independently associated with the final in-hospital mortality. We concluded that the overall mortality of neonatal candidemia has remained consistently high over the past decade. Prompt early catheter removal and an aggressive treatment strategy for neonatal candidemia with septic shock would be critical to improving patient outcomes.

Effect of first-line antifungal treatment on ocular complication risk in Candida or yeast blood stream infection

ObjectivesOcular candidiasis (OC) can complicate Candida bloodstream infection (BSI). Antifungal treatment improves the prognosis of patients with BSI, but the effects of choice and timing of first-line medication on OC...

AmBisome, tres retos: infección por Candida auris, infección del sistema nervioso central e infección asociada a biopelículas

The treatment of invasive fungal infections remains a challenge, both for the diagnosis and for the need of providing the appropriate antifungal therapy. Candida auris is a pathogenic yeast that is responsible for hospital outbreaks, especially in intensive care units; it is characterized by a high resistance to the antifungal agents and can become multidrug-resistant. At present, the recommended antifungal agents for the invasive infections with this pathogen are echinocandins, always after carrying out an antifungal susceptibility testing. In case of no clinical response or persistent candidemia, the addition of liposomal amphotericin B or isavuconazole may be considered. Both fungal infection of the central nervous system and that associated with biomedical devices remain rare entities affecting mainly immunocompromised patients. However, an increase in their incidence in recent years, along with high morbidity and mortality, has been shown. The treatment of these infections is conditioned by the limited knowledge of the pharmacokinetic properties of antifungals. A better understanding of the pharmacokinetic and pharmacodynamic parameters of the different antifungals is essential to determine the efficacy of the antifungal agents in the treatment of these infections.

(1,3)-β-D-glucan is able to predict therapeutic failure of patients with candidemia and not only mortality.

Candidemia is a major cause of bloodstream infection in tertiary hospitals worldwide and fungal biomarkers may provide early diagnosis. To evaluate the performance of (1-3)-β-D-glucan (BDG) in the diagnosis of candidemia and its ability to predict therapeutic failure. This was a prospective, multi-centre study conducted in 3 Brazilian hospitals. Clinical outcome was evaluated along 2weeks of treatment, and therapeutic failure was defined as the occurrence of persistent candidemia, Candida deep-seated infection or death. Baseline BDG detection was performed with the Fungitell® assay (Associates of Cape Cod, Falmouth-USA). We enrolled a total of 71 patients with candidemia and a control group with 110 healthy volunteers. The sensitivity and specificity of BDG for diagnosing candidemia were as follows: 71.8% (95% confidence interval [95% CI] 59.7% - 81.5%) and 98.2% (95% CI 92.9% - 99.7%), respectively. The only predictor of therapeutic failure was a higher BDG value at diagnosis of candidemia; a value>226pg/mL predicted failure with sensitivity and specificity of 75% and 78%, respectively. A high baseline serum BDG value was associated with therapeutic failure.

PERSISTENT FUNGEMIA WITH CANDIDA AURIS IN A PATIENT WITH ENTEROCUTANEOUS FISTULA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Candida auris has been emerging as a fearsome adversary in the severely debilitated and ICU patients with complicated medical course. CASE PRESENTATION: A 61 year old Caucasian female with severe aortic stenosis, complicated diverticulitis, hemicolectomy and entero-cutaneous fistula (ECF), end stage renal disease on hemodialysis presented with several days of increased fistula leakage without any fevers or diarrhea. Initial vitals were stable, ECF with erythematous margins was noted. CBC was normal. CT was negative for peritonitis or perforation. Initial Blood cultures were negative, however urine grew insignificant Klebsiella pneumoniae and Streptococcus. Later, she deteriorated and was shifted to ICU, intubated, and started on vasopressors. Three more blood cultures were negative but the fourth grew Candida duobushaemulonii on VITEK. A bronchoalveolar lavage specimen and urine culture also grew Candida. She continued to have candidemia despite Micafungin. Central line exchange, line holiday and continuous renal replacement therapy were done. She transiently improved and was extubated but had to be promptly reintubated on deterioration. Persistent candidemia raised suspicion for C auris which was confirmed. A transesophageal echocardiogram revealed new mitral and aortic valve vegetations; however, she was a poor candidate for surgical procedures. She deteriorated despite aggressive measures. DISCUSSION: Misidentification of C auris with traditional phenotypic methods prompted CDC to publish guidelines to forward all C duobushaemulonii isolates on VITEK for accurate identification(1). Risk factors for persistent C auris candidemia include extensive surgery, cancers, underlying respiratory illness, diabetes mellitus, organ failure, prolonged ICU stay and previous antifungal exposure(2–4). After outbreaks in Asian(4) and European(5) hospitals, C. auris is emerging in American healthcare. Blood cultures and (1-3)-β-D-glucan assay are specific for diagnosis(3). It is notorious in causing native and prosthetic valve endocarditis(6). Transient candidemia and intestinal translocation result in persistent candidemia via biofilm(6). It’s generally resistant to azoles, susceptible to Echinocandins and Amphotericin B(5), but multidrug resistance is emerging(2,4). Work is ongoing on novel drugs like SCY-078 and VT-1598(2). Management includes early antifungals, removing foreign bodies(5) and may need surgery(6). Risk of biofilms and survivability on inanimate objects(5,6) need contact precautions and strict infection control. CONCLUSIONS: Prompt identification and institution of antifungals with ancillary measures including surgery remain key to successfully treating C auris. Reference #1: 1. Identification of Candida auris | Candida auris | Fungal Diseases | CDC. https://www.cdc.gov/fungal/candida-auris/recommendations.html. Published November 6, 2019. Accessed February 19, 2020. Reference #2: 2. Osei Sekyere J. Candida auris: A systematic review and meta-analysis of current updates on an emerging multidrug-resistant pathogen. MicrobiologyOpen. 2018;7(4):e00578. doi:10.1002/mbo3.578. Reference #3: 3. Xia R, Wang D. Risk factors of invasive candidiasis in critical cancer patients after various gastrointestinal surgeries: A 4-year retrospective study. Medicine (Baltimore). 2019;98(44):e17704. doi:10.1097/MD.0000000000017704. 4. Rudramurthy SM, Chakrabarti A, Paul RA, et al. Candida auris candidaemia in Indian ICUs: analysis of risk factors. J Antimicrob Chemother. 2017;72(6):1794-1801. doi:10.1093/jac/dkx034. 5. Ruiz-Gaitán A, Moret AM, Tasias-Pitarch M, et al. An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital. Mycoses. 2018;61(7):498-505. doi:10.1111/myc.12781. 6. Giuliano S, Guastalegname M, Russo A, et al. Candida endocarditis: systematic literature review from 1997 to 2014 and analysis of 29 cases from the Italian Study of Endocarditis. Expert Rev Anti Infect Ther. 2017;15(9):807-818. doi:10.1080/14787210.2017.1372749. DISCLOSURES: No relevant relationships by Raisa Ghosh, source=Web Response No relevant relationships by Aveek Mukherjee, source=Web Response No relevant relationships by Haris Rana, source=Web Response

Evaluation of the potential virulence of Candida haemulonii species complex and Candida auris isolates in Caenorhabditis elegans as an in vivo model and correlation to their biofilm production capacity

Candida haemulonii species complex (Can. haemulonii sensu stricto, Can. duobushaemulonii and Can. haemulonii var. vulnera) and related species (Can. auris and Can. pseudohaemulonii) have attracted attention due to reduced susceptibility to azoles and amphotericin B. Furthermore, attributes of potential virulence have been recognized in Can. haemulonii species complex and Can. auris, like the capability to form biofilm, which represent the most important risk factors for persistent candidemia. However, the relationship between biofilm production and impact on host mortality is still unclear. To evaluate the potential virulence of Can. haemulonii species complex and Can. auris isolates by correlating biofilm production and capacity to kill Caenorhabditis elegans as an in vivo model. In this study, virulence factors were characterized among a total of sixty-six Can. haemulonii species complex and Can. auris isolates to gain insight about virulence traits of these pathogenic yeasts by evaluating the in vitro biofilm production and potential pathogenicity for Cae. elegans, as an in vivo infection model. All clinical isolates tested were biofilm producer, inter- and intra-specific differences on the biofilm forming capacity by the strains were observed. Can. auris and Can. haemuolonii var. vulnera showed similar biofilm production, both higher than Can. haemulonii sensu stricto and Can. duobushaemulonii. Regarding the virulence of the Cae. elegans model, Can. haemulonii species complex and Can. auris isolates were capable of causing infection in Cae. elegans, and our data suggest that the high biofilm production by Can. haemulonii var. vulnera and Can. duobushaemulonii isolates may impact in the pathogenicity caused on Cae. elegans.