Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center.

BACKGROUND: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. METHODS: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. RESULTS: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87-23.24, p = 0.003). CONCLUSIONS: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death.

Candidemia Following Severe COVID-19 in Hospitalised and Critical Ill Patients: A Systematic Review and Meta-Analysis.

RATIONALE: The epidemiology and clinical impact of COVID-19-associated candidemia (CAC) remained uncertain, leaving gaps in understanding its prevalence, risk factors and outcomes. METHODS: A systematic review and meta-analysis were conducted by searching PubMed, Embase and Scopus for reports of CAC prevalence, risk factors and clinical outcomes up to June 18, 2024. The generalised linear mixed model was employed to determine the prevalence and 95% confidence intervals (CIs). The risk factors and clinical outcomes were compared between patients with and without CAC using the inverse variance method. RESULTS: From 81 studies encompassing 29 countries and involving 351,268 patients, the global prevalence of CAC was 4.33% (95% Cl, 3.16%-5.90%) in intensive care unit (ICU) patients. In ICUs, the pooled prevalence of CAC in high-income countries was significantly higher than that of lower-middle-income countries (5.99% [95% Cl, 4.24%-8.40%] vs. 2.23% [95% Cl, 1.06%-4.61%], p = 0.02). Resistant Candida species, including C. auris, C. glabrata (Nakaseomyces glabratus) and C. krusei (Pichia kudriavzveii), constituted 2% of ICU cases. The mortality rate for CAC was 68.40% (95% Cl, 61.86%-74.28%) among ICU patients. Several risk factors were associated with CAC, including antibiotic use, central venous catheter placement, dialysis, mechanical ventilation, tocilizumab, extracorporeal membrane oxygenation and total parenteral nutrition. Notably, the pooled odds ratio of tocilizumab was 2.59 (95% CI, 1.44-4.65). CONCLUSIONS: The prevalence of CAC is substantial in the ICU setting, particularly in high-income countries. Several risk factors associated with CAC were identified, including several that are modifiable, offering the opportunity to mitigate the risk of CAC.

Candidaemia and Central Line-Associated Candidaemia in a Network of Indian ICUs: Impact of COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.

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.

Relationship between SARS-CoV-2 infection and ICU-acquired candidemia in critically ill medical patients: a multicenter prospective cohort study.

BACKGROUND: While SARS-CoV2 infection has been shown to be a significant risk-factor for several secondary bacterial, viral and Aspergillus infections, its impact on intensive care unit (ICU)-acquired candidemia (ICAC) remains poorly explored. METHOD: Using the REA-REZO network (French surveillance network of ICU-acquired infections), we included all adult patients hospitalized for a medical reason of admission in participating ICUs for at least 48 h from January 2020 to January 2023. To account for confounders, a non-parsimonious propensity score matching was performed. Rates of ICAC according to SARS-CoV2 status were compared in matched patients. Factors associated with ICAC in COVID-19 patients were also assessed using a Fine-Gray model. RESULTS: A total of 55,268 patients hospitalized at least 48 h for a medical reason in 101 ICUs were included along the study period. Of those, 13,472 were tested positive for a SARS-CoV2 infection while 284 patients developed an ICAC. ICAC rate was higher in COVID-19 patients in both the overall population and the matched patients' cohort (0.8% (107/13,472) versus 0.4% (173/41,796); p < 0.001 and 0.8% (93/12,241) versus 0.5% (57/12,241); p = 0.004, respectively). ICAC incidence rate was also higher in those patients (incidence rate 0.51 per 1000 patients-days in COVID-19 patients versus 0.32 per 1000 patients-days; incidence rate ratio: 1.58 [95% CI:1.08-2.35]; p = 0.018). Finally, patients with ICAC had a higher ICU mortality rate (49.6% versus 20.2%; p < 0.001). CONCLUSION: In this large multicenter cohort of ICU patients, although remaining low, the rate of ICAC was higher among COVID-19 patients.

Experimental study of specific and nonspecific blood culture bottles for the diagnosis of candidemia.

BACKGROUND: Early diagnosis of candidemia is critical for the correct management and treatment of patients. AIMS: To test the efficacy of different blood culture bottles in the growth of Candida strains. METHODS: We compared the performance of BD BACTEC™ Plus Aerobic/F (Aero) culture bottles with the specific BD BACTEC™ Mycosis IC/F Lytic (Myco) culture bottles using the BD BACTEC™ FX 40 automated blood culture system to determine the mean time-to-detection (TTD) in Candida species. One isolate each of six Candida species was inoculated into blood culture bottles (final concentration, 1-5CFUml-1) and incubated at 37°C until automated growth detection. RESULTS: Candida albicans and Nakaseomyces glabratus (Candida glabrata) were detected earlier in the specific culture bottle, whereas Candida tropicalis was detected earlier in the nonspecific bottle; Candida parapsilosis, Pichia kudriavzevii (Candida krusei), and Meyerozyma guilliermondii (Candida guilliermondii) presented similar TTD in both bottles. CONCLUSIONS: Our study suggests the suitability of using both bottles in clinical laboratories for a faster diagnosis and prompt starting of any treatment.

"A decade of candidaemia: A comprehensive analysis of prognosis and risk factors at a Belgian tertiary hospital".

Candidemia, predominantly caused by C. albicans, poses a significant threat in hospitals. Yet, non-albicans candidemia (NAC) and antifungal resistance are increasing concerns. This retrospective study at CHU UCL Namur Mont-Godinne, a Belgian university hospital, from January 2013 to February 2023, analyzed 148 candidemia cases. The mean annual incidence was 0.94 per 1000 admissions, with a notable surge in C. albicans cases in 2020, possibly due to COVID-19. Candidemia was most prevalent in the ICU (48 %), with C. albicans (57.1 %) and C. glabrata (18.4 %) being the predominant species and a 30-day mortality rate of 38 %. NAC was significantly higher in the hematology unit (81 %). Notably, no echinocandin resistance was observed, while fluconazoleresistance remained stable at 10 %. NAC was associated with azole resistance. This study provides a decade-long overview of candidemia at CHU UCL Namur Mont-Godinne, offering valuable insights into its epidemiology and clinical characteristics in Belgian hospital settings.

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity.

PURPOSE: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. METHODS: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. RESULTS: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. CONCLUSION: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

Clinical characteristics and outcomes of patients with candidemia during the COVID-19 pandemic: Insights from experience in the Omicron era.

BACKGROUND: In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. METHODS: The incidence of candidemia and fluconazole susceptibility of Candida species before (2015-2019) and during COVID-19 pandemic (2020-2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). RESULTS: Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01-1.03), ICU stay (AOR = 1.84, 95% CI: 1.29-2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03-1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04-2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29-0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38-0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. CONCLUSION: While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.

Nosocomial transmission of fluconazole-resistant Candida glabrata bloodstream isolates revealed by whole-genome sequencing.

The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C. glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles. IMPORTANCE: The prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy.

Multi-state evaluation of Candida infections in burn patients.

BACKGROUND: Burn patients are at high risk of developing secondary invasive fungal infections due to their compromised skin barrier, extensive use of antibiotics, and immunosuppression. OBJECTIVES: We investigated demographic characteristics and clinical factors associated with Candida infections in intensive care unit (ICU) burn patients, and the in vitro antifungal susceptibility of species of isolates. METHODS: A total of 353 burn patients admitted to three major ICUs of burn centers in Iran were evaluated between 2021 and 2023. Patients were considered as colonisation and candidemia. Demographic characteristics, burn-related factors, and clinical conditions were compared among the groups. Furthermore, we identified fungi at the species level and performed antifungal susceptibility testing according to CLSI guidelines. RESULTS: Overall, 46.2% of patients were colonised with a Candida species, leading to candidemia in 15.3%. The most frequently isolated species from candidemia and burn wound colonisation were Candida parapsilosis (37.0%) and Candida albicans (31.9%), respectively. Risk factors linked to candidemia included larger total body surface area (TBSA) (>50%), older patients, indwelling catheters, diabetes, and an extended ICU stay. Mortality rate was higher among candidemia patients (82.5%) compared to colonised patients (7.3%). The resistance rate of the strains isolated from candidemia to fluconazole and voriconazole was 28% and 18.2%, respectively. CONCLUSION: We found that a higher percentage of TBSA burn injuries, longer hospital stays, and catheterization are important predictors of candidemia. The mortality rate was significantly higher in people infected with non-albicans Candida species. Prevention and treatment strategies for candidemia should be based on updated, regional epidemiological data.

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.

Emerging trends in pediatric candidemia: mapping the rise in Candida parapsilosis incidence and antifungal resistance in Turkey.

Candidemia is emerging as a significant concern in children, particularly among those with underlying conditions like malignancies or prematurity. The interpretation of epidemiological data on candidemias and their antifungal resistance plays a vital role in aiding diagnosis and guiding clinicians in treatment decisions. From 2014 to 2021, a retrospective analysis was conducted in Istanbul, Turkey; comparing Candida albicans and non-albicans (NAC) spp in both surviving and deceased groups. Furthermore, an examination of Candida parapsilosis and other species was performed, assessing various clinical and laboratory parameters. Among 93 patients, with a median age of 17 months, C. parapsilosis emerged as the predominant isolated species (44%), followed by C. albicans (34.4%). Resistance to fluconazole, voricanozole, and echinocandins, along with a history of broad-spectrum antibiotic use were found to be significantly higher in the non-albicans Candida group compared to C. albicans group. In the C. parapsilosis group, statistically lower age was identified in comparison to the other groups (P = .018). In addition, high fluconazole and voriconazole resistance was detected in Candida parapsilosis spp. Our study highlights a notable prevalence of C. parapsilosis, particularly in younger children, which is different from similar studies in childhood. This trend may be attributed to the common use of total parenteral nutrition and central venous catheter in gastrointestinal disorders and metabolic diseases. Furthermore, as anticipated, high azole resistance is noted in C. parapsilosis and other non-albicans Candida species. Interestingly, resistance to both amphotericin B and echinocandins within this group has been notably high. It is crucial to emphasize the considerable antifungal resistance seen in C. parapsilosis isolates.

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.

Reducing candidaemia risk in urology patients: Revised algorithm & Pharmacist-Led Implementation.

BACKGROUND: Candidaemia is an invasive infection with high morbidity and mortality. All urology procedures carry risk of post-operative infection. Risk mitigation strategies include preoperative urine culture and treatment of cultured organism(s) regardless of symptoms. After zero cases of candidaemia for two years, there were five cases in elective urology patients within 15 weeks between June - September 2021. This increased incidence of candidaemia amongst these patients prompted multidisciplinary investigation. METHODS: Single centre case series, in a 250-bed hospital which annually performs 2000-2500 elective urology surgeries. Affected patients were elderly with multiple comorbidities. Notably, four of five patients had prior indwelling ureteral stents. All five patients had preoperative bacteriuria requiring antibiotics and one patient had pre-operative candiduria. RESULTS: Hypotheses including sterilisation failure, surgical instrument contamination, or surgical technique issues were unfounded. We propose that pre-operative duration of antibacterial therapy, particularly in the setting of ureteral stent biofilm, is a significant factor for candiduria. A new prescribing algorithm for urology patients was devised. Antibiotic treatment duration in asymptomatic patients with indwelling urinary tract foreign material was reduced from 14 to 3 days, and from 14 to 7 days in symptomatic patients. Dedicated pharmacist resources were allocated to support this change and pre-operatively manage these patients. These interventions led to zero candidaemia cases over the subsequent 21 months, along with zero post-operative bacterial bloodstream infections. CONCLUSIONS: Prolonged pre-operative antibacterial therapy poses a risk for post-operative candidaemia, especially in patients with ureteral stents. Shortening pre-operative antibiotic courses, coupled with increased pharmacist involvement, effectively reduced candidaemia incidence.

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 noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned 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.

Increase in candidemia cases and emergence of fluconazole-resistant Candida parapsilosis and C. auris isolates in a tertiary care academic hospital during the COVID-19 pandemic, Greece, 2020 to 2023.

BackgroundThe COVID-19 pandemic and the emergence of Candida auris have changed the epidemiological landscape of candidaemia worldwide.AimWe compared the epidemiological trends of candidaemia in a Greek tertiary academic hospital before (2009-2018) and during the early COVID-19 (2020-2021) and late COVID-19/early post-pandemic (2022-2023) era.MethodsIncidence rates, species distribution, antifungal susceptibility profile and antifungal consumption were recorded, and one-way ANOVA or Fisher's exact test performed. Species were identified by MALDI-ToF MS, and in vitro susceptibility determined with CLSI M27-Ed4 for C. auris and the EUCAST-E.DEF 7.3.2 for other Candida spp.ResultsIn total, 370 candidaemia episodes were recorded during the COVID-19 pandemic. Infection incidence (2.0 episodes/10,000 hospital bed days before, 3.9 during the early and 5.1 during the late COVID-19 era, p < 0.0001), C. auris (0%, 9% and 33%, p < 0.0001) and fluconazole-resistant C. parapsilosis species complex (SC) (20%, 24% and 33%, p = 0.06) infections increased over time, with the latter not associated with increase in fluconazole/voriconazole consumption. A significant increase over time was observed in fluconazole-resistant isolates regardless of species (8%, 17% and 41%, p < 0.0001). Resistance to amphotericin B or echinocandins was not recorded, with the exception of a single pan-echinocandin-resistant C. auris strain.ConclusionCandidaemia incidence nearly tripled during the COVID-19 era, with C. auris among the major causative agents and increasing fluconazole resistance in C. parapsilosis SC. Almost half of Candida isolates were fluconazole-resistant, underscoring the need for increased awareness and strict implementation of infection control measures.

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.

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.