Insights from Three Pan-European Multicentre Studies on Invasive Candida Infections and Outlook to ECMM Candida IV.

Invasive candidiasis and candidemia remain a significant public health concern. The European Confederation of Medical Mycology (ECMM) conducted three pan-European multicentre studies from 1997 to 2022 to investigate various aspects of invasive Candida infections. These studies revealed shifting trends in Candida species distribution, with an increase of non-albicans Candida species as causative pathogens, increasing rates of antifungal resistance, and persistently high mortality rates. Despite advancements in antifungal treatment, the persistently high mortality rate and increasing drug resistance, as well as limited drug access in low-income countries, underscore the need for continued research and development in the treatment of Candida infections. This review aims to summarize the findings of the three completed ECMM Candida studies and emphasize the importance of continued research efforts. Additionally, it introduces the upcoming ECMM Candida IV study, which will focus on assessing candidemia caused by non-albicans Candida species, including Candida auris, investigating antifungal resistance and tolerance, and evaluating novel treatment modalities on a global scale.

Antifungal susceptibility pattern of Candida auris strains: Analysis of clinical strains in a tertiary-care educational university hospital.

Herein, we aimed to investigate the antifungal susceptibility pattern of Candida auris clinical strains in our setting Bahrain Oncology Center-King Hamad University Hospital-Bahrain. C. auris strains isolated from different clinical specimens in the Microbiology Laboratory from October-2021 to November-2022 were evaluated. Species-level identification of fungi was performed by MALDI-TOF (Bruker, Germany). Minimum inhibitory concentration (MIC) was determined either by E-test strips or by MICRONAUT MIC system based on CDC guidelines for C. auris antifungal interpretation. Fluconazole, amphotericin-B, voriconazole, and caspofungin susceptibility data of the clinical strains were analyzed. A total of 40 clinical isolates were included: 25% were blood culture isolates, 65% were urinary, and 10% were soft tissue isolates. Only 29 strains could be tested for amphotericin-B and 32 for voriconazole. Overall resistance pattern was as follows: 100% resistance to fluconazole, 2.5% resistance to caspofungin, and 0% resistance to amphotericin b. Median voriconazole MIC was 0.015 ug/ml (min 0.08, max= 0.064 ug/ml). We had no fluconazole-sensitive strain and only one caspofungin-resistant strain. A single isolate (2.5%), which was associated with candidemia, demonstrated resistance to two antifungal agents: fluconazole and caspofungin. No triple or quadruple drug resistant strain existed.

Predominance of Candida glabrata in candidemia among patients with solid tumor cancer in Oman: A retrospective study.

Objectives: Candida species frequently cause bloodstream infections; however, there is a lack of epidemiological studies on candidemia in Oman. Methods: To address this, we conducted a retrospective study at Sultan Qaboos Comprehensive Cancer and Research Center from October 2021 to October 2023. Results: Our study identified 27 episodes of candidemia among 26 patients with cancer, with an incidence of 4.9 per 1000 admissions. Non-albicans Candida (NAC) prevailed over C. albicans (70.37% vs 29.62%), with C. glabrata as the predominant NAC species (n = 10; 37%). The 30-day mortality rate was 40.7%, showing no significant difference between NAC and C. albicans but was notably higher in critically ill patients (P = 0.03). Conclusion: In Oman, NAC surpasses C. albicans as a causative pathogen for candidemia with a high mortality rate.

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.

Recurrent Fungemia Due to Candida auris.

We present a case of recurrent multidrug-resistant Candida auris (C. auris) in a patient who required multiple hospitalizations. The patient's case was complicated by interval admissions to the intensive care unit for septic and hypovolemic shock for 12 months to manage C. auris fungemia. Despite adequate isolation precautions and appropriate antifungal treatment, this case demonstrates the profound implications of this emerging pathogen, specifically regarding invasive infections. Moreover, C. auris is rapidly becoming known as a multidrug-resistant organism, which limits treatment options and thus contributes to high mortality.

Spontaneous Remission of Acute Lymphoblastic Leukemia Following Candida tropicalis Fungemia.

Spontaneous remission (SR) in acute lymphoblastic leukemia (ALL) is a poorly understood phenomenon that has been sporadically reported in medical literature for over a century, and the molecular and immunologic mechanisms of remission pose interesting clinical questions. Furthermore, the often-transient nature of these remissions poses a challenge to physicians in formulating an approach to treatment. We report on a rare case of Candida tropicalis sepsis in a three-year-old female with high-risk ALL who received less than two months of treatment prior to sepsis and subsequent SR.

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia.

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.

Epidemiology of candidemia during COVID-19 pandemic era in a teaching hospital: A non-concurrent cohort study.

During the COVID-19 pandemic, an increase in the incidence of bloodstream infections caused by fungi of the Candida genus, also known as candidemia, was observed in patients with SARS-CoV-2 infection. This study aimed to assess the incidence of candidemia, the factors related to COVID-19-associated candidemia (CAC), and prognostic factors. A non-concurrent cohort of 87 cases of patients aged over 18 years with candidemia between March 2020 and February 2022 was evaluated. Incidence density (ID) was calculated by the number of patient-days during the period. All causes of mortality within 30 days of observation were considered. Logistic regression and Cox proportional hazards regression were used, respectively, to determine factors associated with CAC and prognostic factors. Values <0.05 were considered significant. The ID of CAC was eight times higher than candidemia in patients without COVID-19 [2.40 per 1000 person-days vs. 0.27 per 1000 person-days; P < .01]. The corticosteroid therapy was as an independent factor associated with CAC [OR = 15.98 (3.64-70.03), P < .01], while abdominal surgery was associated with candidemia in patients without COVID-19 [OR = 0.09 (0.01-0.88), P = .04]. Both patients with and without COVID-19 had a high 30 days-mortality rate (80.8% vs. 73.8%, respectively; P = .59). Liver disease [HR = 3.36 (1.22-9.27); P = .02] and the Charlson score [HR = 1.17 (1.01-1.34); P = .03] were independent factors of death, while the use of antifungals [HR = 0.15 (0.07-0.33); P < .01] and removal of the central venous catheter [HR = 0.26 (0.12-0.56); P < .01] independently reduced the risk of death. These findings highlight the high incidence of candidemia in COVID-19 patients and its elevated mortality.

This study found that bloodstream infections by Candida spp. were significantly more common in patients with than without COVID-19, and Candida glabrata played a significant role in these infections. Liver disease and a higher number of comorbidities were associated with an increased risk of death.

Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was non-inferior to caspofungin for Day 30 all-cause mortality (ACM) and Day 14 global cure in the Phase 3 ReSTORE trial (NCT03667690). We conducted pre-planned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization, or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included Day 30 ACM, Day 14 global cure rate, and Day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively: Day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval] 4.6% [-13.7, 23.5]); Day 14 global response was 55.3% and 50.0% (between-group difference 5.3% [-16.1, 26.0]); and Day 5 mycological eradication was 71.1% and 50.0% (between-group difference 21.1% [-0.2, 40.2]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

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.

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.

Epidemiology of Candidemia in Mashhad, Northeast Iran: A Prospective Multicenter Study (2019-2021).

Candidemia is a major cause of morbidity and mortality in health care settings, and its epidemiology is changing. In the last two decades, the proportion of non-albicans Candida (NAC) yeasts in candidemia has increased. These yeasts more often display resistance to common antifungals. In many western countries, candidemia is mainly caused by susceptible C. albicans, while in resource-limited countries, including Iran, the candidemia species distribution is studied less often. Here, we investigated the species distribution, resistance levels, and characteristics of patients with candidemia in five hospitals in Mashhad (northeast Iran) for two years (2019-2021). Yeast isolates from blood were identified with MALDI-TOF MS and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method, while molecular genotyping was applied to Candida parapsilosis isolates. In total, 160 yeast isolates were recovered from 160 patients, of which the majority were adults (60%). Candidemia was almost equally detected in men (48%) and women (52%). Almost half of patients (n = 67, 49%) were from intensive care units (ICUs). C. parapsilosis (n = 58, 36%) was the most common causative agent, surpassing C. albicans (n = 52, 33%). The all-cause mortality rate was 53%, with C. albicans candidemia displaying the lowest mortality with 39%, in contrast to a mortality rate of 59% for NAC candidemia. With microbroth AFST, nearly all tested isolates were found to be susceptible, except for one C. albicans isolate that was resistant to anidulafungin. By applying short tandem repeat (STR) genotyping to C. parapsilosis, multiple clusters were found. To summarize, candidemia in Mashhad, Iran, from 2019 to 2021, is characterized by common yeast species, in particular C. parapsilosis, for which STR typing indicates potential nosocomial transmission. The overall mortality is high, while resistance rates were found to be low, suggesting that the high mortality is linked to limited diagnostic options and insufficient medical care, including the restricted use of echinocandins as the first treatment option.

Comparative efficacies of the three echinocandins for Candida auris candidemia: real world evidence from a tertiary centre in India.

Though echinocandins are the first line of therapy for C. auris candidemia, there is little clinical data to guide the choice of therapy within this class. This was the first study to compare the three echinocandins in terms of efficacy and outcomes for C. auris candidemia. This was a retrospective analysis of 82 episodes of candidemia caused by C. auris comparing outcomes across the three echinocandins. Majority patients in our study were treated with micafungin. Susceptibility rates were the lowest for caspofungin (35.36% resistance), with no resistance reported for the other two echinocandins. When a susceptible echinocandin was chosen, caspofungin resistance was not a factor significantly associated with mortality. Also, when a susceptible echinocandin was used for therapy, the choice within the class did not affect clinical cure, microbiological cure, or mortality (P > 0.05 for all). Failure to achieve microbiological cure (P = 0.018) and receipt of immune-modulatory therapy (P = 0.01) were significantly associated with increased mortality. Significant cost variation was noted among the echinocandins. Considering the significant cost variation, comparable efficacies can be reassuring for the prescribing physician.

This is the first study comparing efficacy of the three echinocandins in C. auris candidemia. The clinical efficacy of the three echinocandins was found to be comparable. Micafungin and anidulafungin had lower minimum inhibitory concentrations. A significant cost variation was noted.

Candida auris central line-associated blood stream infection in critically ill patients: the worst end of a bad scenario.

BACKGROUND: Candida auris (C. auris) is an emerging aggressive pathogen that causes severe infections in critically ill patients. Therefore, the assessment of this pathogen, characterized by inclination for biofilm formation, elevated colonization rate, and resistance to multiple drugs, holds a paramount importance. There is no data regarding the isolation of C. auris in our tertiary care hospitals' intensive care units (ICUs). The current case study was arranged to assess the incidence of C. auris central line-associated bloodstream infection (CLABSI) problem in our (ICUs). METHODS: Specimens of central venous catheter blood, peripheral blood, and catheter tips were collected from 301 critically ill patients with suspected (CLABSI). Microbiological cultures were utilized to diagnose bacterial and fungal superinfections. The fungal species identification and antifungal susceptibility testing were conducted using the Brilliance Chrome agar, VITEK® 2 compact system, and MALDI-TOF MS. RESULTS: All included specimens (100%) yielded significant growth. Only 14 specimens (4.7%) showed fungal growth in the form of different Candida species. When comparing the identification of C. auris, MALDI-TOF MS is considered the most reliable method. Brilliance CHROMagar demonstrated a sensitivity of 100%, whereas VITEK only showed a sensitivity of approximately 33%. All recovered isolates of C. auris were fluconazole resistant. CONCLUSION: C. auris is a highly resistant emerging pathogen in our ICUs that is often overlooked in identification using conventional methods.

Evaluation of candidemia risk factors and Candida species distribution in intensive care units among patients with and without COVID-19.

OBJECTIVES: To assess the risk variables related to the types of candidemia for each patient, who was admitted into the intensive care unit regardless of the patient with or without complete diagnosis of COVID-19, during the period of March 2019 to December 2022. METHODS: The evaluation comparison of demographic and clinical data of COVID-19 positive and negative patients with candidemia confirmed in blood, 113 cases were assessed. Variables such as gender, age, age of hospitalization, history of hospitalization, concurrently infection, The acute physiology and chronic health evaluation-II scores, comorbidity checking, intubation, central venous catheter use, parenteral nutrition use, steroid use, antibiotic use, lymphopenia, and laboratory variables were evaluated. Candida species distribution, antifungal susceptibility in blood culture were determined. RESULTS: Coronavirus disease-19 was present in 62.8% of cases confirmed candidemia, and these cases were significantly different from COVID-19 negative cases. Significance was found in more intubation, central venous catheter use, parenteral nutrition, and steroid therapy in Group 2. There was no significance with species distribution and associated infection. In total, COVID-19 positive had higher hemoglobin, aspartate aminotransferase, alanine transaminase, and white blood cell levels, which may be associated with the possibility of revealing and controlling candidemia. CONCLUSION: Candida albicans and Candida Parapsilosis (C. parapsilosis) are the species seen in infected COVID-19 patients, while C. parapsilosis and Candida tropicalis are found in non-COVID-19 ones. Risk factors were intubation, parenteral nutrition, central venous catheter, and steroid in the COVID-19 group.

Fungal Foe and Mechanical Hearts: A Retrospective Case Series on Candida auris Bloodstream Infection With Left Ventricular Assist Devices.

No guidelines currently exist for the management of Candida auris bloodstream infection in patients with left ventricular assist devices (LVADs). We aim to share our management experience through this retrospective case series outlining 15 episodes of C auris candidemia identified in 7 patients over 18 months. The initial source of candidemia was central venous catheter in 5 patients, driveline exit site infection in 1 patient, and possible pump infection in 1 patient. All patients were initially treated with micafungin. Despite susceptibility to micafungin, 4 patients experienced recurrent C auris candidemia. All patients died within 1 year of their first episode of C auris candidemia. Source control is challenging in patients with LVADs, and strict infection prevention measures should be practiced. More studies are needed to evaluate the role of newer antifungal agents, use of combination antifungal regimens, and impact on morbidity in patients with LVADs.

Risk analysis of candidemia and its effect on mortality in COVID 19 and non COVID 19 patients.

Background and Objectives: Candidemia is the most common serious fungal infection in critically ill patients in intensive care units (ICU). It series fourth among bloodstream infectious agents. In this study, candidemia risk analysis was examined in COVID 19 and non-COVID 19 patients during the pandemic period. Materials and Methods: COVID 19 and non-COVID 19 cases who were followed up with candidemia in the ICU of our hospital were retrospectively screened. Demographic data, intubation, central venous catheter (CVC), medications, and total parenteral nutrition (TPN) status were evaluated in terms of risk between the two groups. Isolated Candida species and susceptibilty were evaluated. Results: When age, gender, medication, intubation, TPN and CVC were evaluated, no difference was seen in terms of risk. Differences were detected in terms of comorbidities. While the most frequently identified Candida species was C. albicans, the most frequently detected species in the COVID19 patient group was C. parapsilosis. Conclusion: There was no difference in candidemia incidence and risk factors between the two groups. Since candidemias were evaluated in terms of comorbidities, it was determined that Diabetes Mellitus (DM) and chronic obstructive pulmoner disease (COPD) were more common in patients with COVID 19 and less common in coronary artery disease (CAD) and malignancy.

The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.