A machine learning model for early candidemia prediction in the intensive care unit: Clinical application.

Candidemia often poses a diagnostic challenge due to the lack of specific clinical features, and delayed antifungal therapy can significantly increase mortality rates, particularly in the intensive care unit (ICU). This study aims to develop a machine learning predictive model for early candidemia diagnosis in ICU patients, leveraging their clinical information and findings. We conducted this study with a cohort of 334 patients admitted to the ICU unit at Ji Ning NO.1 people's hospital in China from Jan. 2015 to Dec. 2022. To ensure the model's reliability, we validated this model with an external group consisting of 77 patients from other sources. The candidemia to bacteremia ratio is 1:1. We collected relevant clinical procedures and eighteen key examinations or tests features to support the recursive feature elimination (RFE) algorithm. These features included total bilirubin, age, platelet count, hemoglobin, CVC, lymphocyte, Duration of stay in ICU and so on. To construct the candidemia diagnosis model, we employed random forest (RF) algorithm alongside other machine learning methods and conducted internal and external validation with training and testing sets allocated in a 7:3 ratio. The RF model demonstrated the highest area under the receiver operating characteristic (AUC) with values of 0.87 and 0.83 for internal and external validation, respectively. To evaluate the importance of features in predicting candidemia, Shapley additive explanation (SHAP) values were calculated and results revealed that total bilirubin and age were the most important factors in the prediction model. This advancement in candidemia prediction holds significant promise for early intervention and improved patient outcomes in the ICU setting, where timely diagnosis is of paramount crucial.

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

INTRODUCTION: Blood 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. METHODS: This 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. RESULTS: 10 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. CONCLUSION: Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

Clinical evaluation of the T2Candida assay for the rapid diagnosis of candidemia.

We evaluated the clinical performance of the T2Candida assay. The overall agreement of the T2Candida assay results with the blood culture results was 95.3 % (121/127). The T2Candida assay detected three Candida albicans/tropicalis-positive specimens and one Candida krusei/glabrata-positive specimen; however, it did not detect two Candida glabrata specimens.

Prediction of candidemia with machine learning techniques: state of the art.

In this narrative review, we discuss studies assessing the use of machine learning (ML) models for the early diagnosis of candidemia, focusing on employed models and the related implications. There are currently few studies evaluating ML techniques for the early diagnosis of candidemia as a prediction task based on clinical and laboratory features. The use of ML tools holds promise to provide highly accurate and real-time support to clinicians for relevant therapeutic decisions at the bedside of patients with suspected candidemia. However, further research is needed in terms of sample size, data quality, recognition of biases and interpretation of model outputs by clinicians to better understand if and how these techniques could be safely adopted in daily clinical practice.

Candida is a type of fungus that can cause fatal infections. To confirm the presence of the infection, doctors may search for the fungus in the blood. Here, we discuss if computer systems can help to identify infection more easily and more rapidly.

A privacy-preserving platform oriented medical healthcare and its application in identifying patients with candidemia.

Federated learning (FL) has emerged as a significant method for developing machine learning models across multiple devices without centralized data collection. Candidemia, a critical but rare disease in ICUs, poses challenges in early detection and treatment. The goal of this study is to develop a privacy-preserving federated learning framework for predicting candidemia in ICU patients. This approach aims to enhance the accuracy of antifungal drug prescriptions and patient outcomes. This study involved the creation of four predictive FL models for candidemia using data from ICU patients across three hospitals in China. The models were designed to prioritize patient privacy while aggregating learnings across different sites. A unique ensemble feature selection strategy was implemented, combining the strengths of XGBoost's feature importance and statistical test p values. This strategy aimed to optimize the selection of relevant features for accurate predictions. The federated learning models demonstrated significant improvements over locally trained models, with a 9% increase in the area under the curve (AUC) and a 24% rise in true positive ratio (TPR). Notably, the FL models excelled in the combined TPR + TNR metric, which is critical for feature selection in candidemia prediction. The ensemble feature selection method proved more efficient than previous approaches, achieving comparable performance. The study successfully developed a set of federated learning models that significantly enhance the prediction of candidemia in ICU patients. By leveraging a novel feature selection method and maintaining patient privacy, the models provide a robust framework for improved clinical decision-making in the treatment of candidemia.

Systematic Review of Candidemia in Brazil: Unlocking Historical Trends and Challenges in Conducting Surveys in Middle-Income Countries.

INTRODUCTION: Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts. METHODS: We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia. RESULTS: Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered. CONCLUSION: Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Rapid identification,fluconazole and micafungin susceptibility testing of Candida species from blood culture by a short incubation method.

This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.

Unresolved issues in the diagnosis of catheter related candidemia: A position paper / Cuestiones no resueltas en el diagnóstico de la candidemia relacionada con el catéter: un documento de opinión

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper. (AU)

La incidencia y las tendencias recientes de la candidemia y la contribución de la pandemia de COVID-19 a su evolución no están bien documentadas. El catéter es uno de los principales focos de infecciones por Candida spp., pero los métodos empleados para confirmar el origen de la candidemia siguen basándose en los datos generados para la infección bacteriana. La presencia de Candida spp. en la punta de un catéter retirado es el método de referencia para la confirmación, pero no siempre es posible proceder a dicha retirada. Los métodos conservadores, sin retirada del catéter, no han sido estudiados específicamente para microorganismos cuyos tiempos de crecimiento son diferentes a los de las bacterias y, por tanto, estos resultados no son aplicables a la candidemia. Las diferentes especies de Candida spp. no tienen un tropismo particular para la colonización del catéter y los biomarcadores fúngicos, aún no han podido contribuir a la determinación del origen de la candidemia. Técnicas como la resonancia magnética T2MR todavía no se ha empleado para este fin. Por último, todavía no existe un consenso sobre cómo proceder cuando se aísla Candida spp. en un catéter extraído y los hemocultivos obtenidos por venas periféricas simultáneas son negativos. Ante esta falta de datos firmes, un grupo de expertos ha formulado una serie de preguntas y ha tratado de responderlas en base a la literatura, indicando las carencias presentes y ofreciendo su propia opinión. Todos los autores están de acuerdo con las conclusiones del manuscrito y lo ofrecen como documento de posición y discusión. (AU)

Bloodstream infection caused by Wickerhamiella pararugosa in a patient with intestinal obstruction: A case report.

The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4-8 and 0.06 µg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient.

Evaluation of Candidemia in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients have high rates of invasive fungal infections. Candida species are the most commonly isolated fungi. Our aim was to identify risk factors, clinical presentations, and outcomes of candidemia in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated adult (≥18 years old) transplant recipients seen from May 2011 to December 2022 at Baskent University Ankara Hospital. From medical records, we retrospectively reviewed age, sex, transplant type, candidemia agent, risk factors, concomitant infections, and mortality of patients with Candida detected in blood culture. We used SPSS statistics software (version 25) to analyze data. RESULTS: There were 1080 organ transplants performed during the study period (717 kidney, 279 liver, 84 heart). There were 855 who were ≥18 years (655 kidney, 127 liver, 73 heart), of whom candidemia was detected in 26 (16 male; 11 kidney, 11 liver, 4 heart) with a median age of 47.5 years. The most common agents were Candida albicans and Candida glabrata. The most common chronic diseases were hypertension, cirrhosis, and cardiomyopathy. Eighteen patients had a concomitant focus of infection. Ten patients had pneumonia accompanying candidemia. The 30-day mortality rate was as high as 53.8%. The mean duration of candidemia after transplant was 23 months. Catheter-related candidemia was observed in 65% of patients. The 30-day mortality was found to be significantly higher in patients followed in the intensive care unit (P = .014), receiving total parenteral nutrition (P = .001), using broad-spectrum antibiotics (P = .001), and having pneumonia (P = .042) accompanying candidemia. CONCLUSIONS: For adult solid-organ transplant recipients with candidemia, careful monitoring is essential for successful management of total parenteral nutrition, central catheter, use of broadspectrum antibiotics, and invasive interventions.

Evaluation of the mannan antigen assay in neonates with or without Candida albicans colonization.

Mannan antigen (MA) in neonates as a marker of invasive candidemia is not well studied, although 4% of all neonatal intensive care unit admissions are attributed to Candida spp. infections. The aim of this case-control study was to evaluate the performance of MA (Platelia™ Candida AgPluskit, Bio-Rad) in neonates who had rectal Candida colonization or in non-colonized controls. We cultured 340 rectal swabs of neonates and MA was negative in 24/25 C. albicans colonized (96% specificity) and in 30/30 non-colonized neonates (100% specificity). The results indicate a high specificity of the assay, which could be useful in neonates with possible candidemia.

The present study aimed to evaluate the use of mannan antigen (MA) assay in a neonatal unit and compared between C. albicans colonized and non-colonized infants. According to our results, MA found to have high specificity in both groups.

The added value of (1,3)-ß-D-glucan for the diagnosis of Invasive Candidiasis in ICU patients: a prospective cohort study.

PURPOSE: Beta-D-Glucan (BDG) testing has been suggested to support the diagnosis of candidemia and invasive candidiasis. The actual benefit in critically ill high-risk patients in intensive care units (ICU) has not been verified so far. METHODS: In ICU patients receiving empirical echinocandin treatment for suspected invasive candidiasis (IC), serial BDG testing using the Fujifilm Wako Beta-Glucan Test was performed, starting on the first day of echinocandin administration and every 24-48 h afterwards. Diagnostic accuracy was determined for single testing and serial testing strategies using a range of cut-off values. In addition, we compared the added value of these testing strategies when their results were introduced as additional predictors into a multivariable logistic regression model controlling for established risk factors of IC. RESULTS: A total of 174 ICU patients, forty-six of which (25.7%) classified as cases of IC, were included in our study. Initial BDG testing showed moderate sensitivity (74%, 95%CI 59-86%) and poor specificity (45%, 95% CI 36-54%) for IC which could hardly be improved by follow-up testing. While raw BDG values or test results obtained with very high thresholds improved the predictive performance of our multivariable logistic regression model for IC, neither single nor serial testing with the manufacturer-proposed low-level cut-off showed substantial benefit. CONCLUSIONS: In our study of critically ill intensive care patients at high risk for candidemia or invasive candidiasis, diagnostic accuracy of BDG testing was insufficient to inform treatment decisions. Improved classification was only achieved for cases with very high BDG values.

Application of machine learning for mortality prediction in patients with candidemia: Feasibility verification and comparison with clinical severity scores.

BACKGROUND: Clinical severity scores, such as acute physiology, age, chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), Pitt Bacteremia Score (PBS), and European Confederation of Medical Mycology Quality (EQUAL) score, may not reliably predict candidemia prognosis owing to their prespecified scorings that can limit their adaptability and applicability. OBJECTIVES: Unlike those fixed and prespecified scorings, we aim to develop and validate a machine learning (ML) approach that is able to learn predictive models adaptively from available patient data to increase adaptability and applicability. METHODS: Different ML algorithms follow different design philosophies and consequently, they carry different learning biases. We have designed an ensemble meta-learner based on stacked generalisation to integrate multiple learners as a team to work at its best in a synergy to improve predictive performances. RESULTS: In the multicenter retrospective study, we analysed 512 patients with candidemia from January 2014 to July 2019 and compared a stacked generalisation model (SGM) with APACHE II, SOFA, PBS and EQUAL score to predict the 14-day mortality. The cross-validation results showed that the SGM significantly outperformed APACHE II, SOFA, PBS, and EQUAL score across several metrics, including F1-score (0.68, p < .005), Matthews correlation coefficient (0.54, p < .05 vs. SOFA, p < .005 vs. the others) and the area under the curve (AUC; 0.87, p < .005). In addition, in an independent external test, the model effectively predicted patients' mortality in the external validation cohort, with an AUC of 0.77. CONCLUSIONS: ML models show potential for improving mortality prediction amongst patients with candidemia compared to clinical severity scores.

Evaluation of the Performance of the Dynamiker Fungus (1-3)-ß-D-Glucan and Fungitell Assay for Diagnosis of Candidemia: Need for New Cut-off Development and Test Validation.

(1-3)-Beta-D Glucan (BDG) detection has shown to be a highly effective tool to diagnose invasive fungal infections. Therefore, this study aimed to compare clinical characteristics of the Fungitell (FA) and Dynamiker Fungus (1-3)-ß-D-Glucan assay (DFA) for the diagnosis of candidemia. Using DFA and FA, the BDG levels of 57 serum samples from case and control groups were determined. The kappa coefficient (κ) and Spearman's rank correlation (rs) were used to examine the consistency of assays on a quantitative and qualitative level, respectively. The sensitivity, specificity, and accuracy were 94.6 %, 65.0 %, and 87.7% for DFA, and 94.6 %, 75.0 %, and 89.4 % for FA, respectively. The performance of the DFA for the diagnosis of candidemia was highly consistent with that of the FA, both quantitatively (rs: 0.9) and qualitatively (kappa = 0.78). Collectively, the DFA assay performed excellently in comparison to the FA for the diagnosis of candidemia.

Identification of two anti-Candida antibodies associated with the survival of patients with candidemia.

IMPORTANCE: Candidemia (bloodstream invasion by Candida species) is a major fungal disease in humans. Despite the recent progress in diagnosis and treatment, therapeutic options are limited and under threat of antimicrobial resistance. The disease mortality remains high (around 40%). In contrast with deep-seated invasive candidiasis, particularly that occurring in patients with hematologic malignancies and organ transplants, patients with candidemia are often not immunocompromised and therefore able to mount memory anticandidal immune responses, perhaps primed by Candida commensalism. We investigated antibody immunity in candidemia patients and report here on the ability of these patients to produce antibodies that react with Candida antigens. In particular, the patients with high titers of IgG reactive with two immunodominant, virulence-associated antigens (Als3 and MP65) had a higher 30-day survival. If confirmed by controlled, prospective clinical studies, our data could inform the development of antibody therapy to better treat a severe fungal infection such as candidiasis.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Utility of incorporation of beta-D-glucan and T2Candida testing for diagnosis and treatment of candidemia.

The additive role of non-culture-based methods for the diagnosis of candidemia remains unknown. We evaluated 2 clinical practices followed in our hospitals for the diagnosis of candidemia, namely practice#1 including a combination of blood cultures and T2Candida, and practice#2 that also included Beta-D-glucan (BDG). Three out of 96 patients testing positive with practice#1 received a complete antifungal course. Of the 120 patients evaluated with practice#2, 29 were positive. Only 55.2% of those received a complete course. We observed significant differences in antifungal utilization, with 268.5 antifungal days/1000 patient-days for practice#1, as opposed to 371.9 days for practice#2, a nearly 40% difference. However, we found similar rates of antifungal discontinuation among negative patients at 3 days of testing (36.8% and 37.0% respectively). No differences were detected in death and/or subsequent diagnosis of candidemia. In summary, addition of BDG was interpreted variably by clinicians, was associated with an increase in antifungal utilization, and did not correlate with measurable clinical benefits for patients.