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.

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.

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.

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.

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.

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-a systematic review to inform the world health organization fungal priority pathogens list.

The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.

Initial micafungin treatment does not improve outcomes compared to fluconazole treatment in immunocompromised and critically ill patients with candidaemia.

BACKGROUND: Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES: To understand optimal initial treatment of candidaemia. METHODS: We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS: A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS: These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.

Implication of genotypes for prognosis of Candida glabrata bloodstream infections.

BACKGROUND: Genotyping isolates of a specific pathogen may demonstrate unique patterns of antimicrobial resistance, virulence or outcomes. However, evidence for genotype-outcome association in Candida glabrata is scarce. We aimed to characterize the mycological and clinical relevance of genotypes on C. glabrata bloodstream infections (BSIs). METHODS: Non-duplicated C. glabrata blood isolates from hospitalized adults were genotyped by MLST, and further clustered by the unweighted pair group method with arithmetic averages (UPGMA). A clonal complex (CC) was defined by UPGMA similarities of >90%. Antifungal susceptibility testing was performed by a colorimetric microdilution method and interpreted following CLSI criteria. RESULTS: Of 48 blood isolates evaluated, 13 STs were identified. CC7 was the leading CC (n = 14; 29.2%), including 13 ST7. The overall fluconazole and echinocandin resistance rates were 6.6% and 0%, respectively. No specific resistance patterns were associated with CC7 or other CCs. Charlson comorbidity index (adjusted OR, 1.49; 95% CI, 1.05-3.11) was the only predictor for CC7. By multivariable Cox regression analyses, CC7 was independently associated with 28 day mortality [adjusted HR (aHR), 3.28; 95% CI, 1.31-8.23], even after considering potential interaction with neutropenia (aHR, 3.41; 95% CI, 1.23-9.42; P for interaction, 0.24) or limited to 34 patients with monomicrobial BSIs (aHR, 2.85; 95% CI, 1.15-7.08). Also, the Kaplan-Meier estimate showed greater mortality with CC7 (P = 0.003). Fluconazole resistance or echinocandin therapy had no significant impact on mortality. CONCLUSIONS: Our data suggested comorbid patients were at risk of developing CC7 BSIs. Further, CC7 was independently associated with worse outcomes.

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.

In vitro activity of taurolidine against clinical Candida auris isolates: relevance to catheter-related bloodstream infections.

Candida auris is an evolving and concerning global threat. Of particular concern are bloodstream infections related to central venous catheters. We evaluated the activity of taurolidine, a broad-spectrum antimicrobial in catheter lock solutions, against 106 C. auris isolates. Taurolidine was highly active with a MIC50/MIC90 of 512/512 mg/L, over 20-fold lower than lock solution concentrations of ≥13,500 mg/L. Our data demonstrate a theoretical basis for taurolidine-based lock solutions for prevention of C. auris catheter-associated infections.

Candida parapsilosis candidemia in children admitted to a tertiary hospital in Turkey: clinical features and antifungal susceptibility.

In recent years, the incidence and drug resistance of Candida parapsilosis have increased. Our study aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. Two hundred pediatric patients with C. parapsilosis candidemia were included in the study between 1 January 2010 and 1 August 2023. Clinical samples were evaluated on a BACTEC-FX-40 automatic blood culture device (Becton Dickinson, USA). Yeast isolates were identified to the species level via identification cards (YST) using the VITEK 2 Compact (bioMeriéux, France) system. Antifungal susceptibility was performed using antifungal cell cards (AST-YST01). Approval for the study was received from the "University Faculty of Medicine" Hospital Clinical Research Ethics Committee. Non-catheter candidemia was detected in 127 (63.5%) patients, and catheter-related candidemia was detected in 73 (36.5%) patients. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care unit stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy. We think that our study can provide important information about the clinical profiles, distributions, susceptibility profiles, and control of antifungal resistance of C. parapsilosis isolates. IMPORTANCE: It has been observed that the frequency and antifungal resistance of Candida parapsilosis have increased recently. In our study, we aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy.

An Alarming Rise of Candidemia Caused by Non-Albicans Candida Species in Intensive Care Unit in Mymensingh, Bangladesh.

In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.

Factors influencing outcomes in candidemia: A retrospective study of patients in a Swedish county.

BACKGROUND: Candidemia is a diverse condition and associated with a broad spectrum of clinical presentation. As mortality is high, timely diagnosis of candidemia and start of correct therapeutic treatment are essential. OBJECTIVES: To investigate characteristics and factors influencing outcomes for patients with candidemia in a Swedish setting. METHOD: All positive blood cultures for any Candida species in Östergötland County from 2012 to 2016 were screened. Medical records of patients fulfilling all inclusion criteria and no exclusion criteria were retrospectively reviewed to obtain data on risk factors, diagnostic and therapeutic procedures and at what wards candidemia was diagnosed. Univariate logistic regression and multivariable regression analysis were used to obtain odds ratio to determine risk factors for 30-day all-cause mortality associated with candidemia. A p-value <.05 was considered statistically significant. RESULTS: Of all analysed risk factors, increasing age, renal failure with haemodialysis, immunosuppressant treatment, and severity of the infection (i.e. if septic shock was present) were significantly associated with 30-day mortality in univariate analysis (p < .05). Removal of a central venous catheter or an infectious diseases consultant was associated with a significantly lower odds ratio for death at 30 days (p < .05). With multivariable analysis, age, time to start of treatment and infectious disease consultant remained significant (p < .05). CONCLUSION: In conclusion, this study provides an update of the epidemiology and outcomes of candidemia in a Swedish setting, highlighting that patients with candidemia are present at various departments and indicates the importance of an infectious disease consultant when candidemia is present.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study.

BACKGROUND: As limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6-10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. METHODS: A retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. RESULTS: Of 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0-76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01-0.63; P = 0.005). CONCLUSION: Short courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Antifungal susceptibility and virulence determinants profile of candida species isolated from patients with candidemia.

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.

Analysis of candidemia cases in a city hospital during the COVID-19 pandemic.

OBJECTIVE: The frequency and mortality of candidemia remain important. Non-albicans Candida species such as C. auris are increasing. PATIENTS AND METHODS: A retrospective review of adult patients diagnosed with bloodstream infection due to Candida species in the 17 months between July 1, 2020, and December 1, 2021, was performed. Yeast colonies grown in culture were identified by matrix-assisted laser desorption/ionization time-of-flight. Antifungal susceptibility tests of Candida strains were performed with Sensititre YeastOne (TREK Diagnostic Systems Inc., Westlake, Ohio) kits, and minimum inhibitory concentration values were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints. RESULTS: In total, 217 patients (mean age 64.9±15.7 years) were included. C. albicans was the most common fungus (detected in 82 patients; 37.8%), followed by C. parapsilosis (17.1%), C. glabrata (15.2%), C. tropicalis (15.2%), and C. auris (9%). Candidemia developed in 175 (81.4%) of the cases during their intensive care unit stay. Fluconazole (41.0%) and caspofungin (36.4%) were the two most frequently used antifungal agents in antifungal therapy. There were 114 (52.3%) deaths in the study group. Mortality rates were found to be lower in patients infected with C. parapsilosis or C. auris. Age and previous COVID-19 infection were other important risk factors. When the 217 Candida spp. were examined, resistance and intermediate susceptibility results were higher when EUCAST criteria were used. While the two methods were found to be fully compatible only for fluconazole, a partial agreement was also observed for voriconazole. CONCLUSIONS: As our study observed, the COVID-19 pandemic brought increasing numbers of immunosuppressed patients, widespread use of antibacterials, and central venous catheters, increasing the frequency and mortality of candidemia cases. All health institutions should be prepared for the diagnosis and treatment of candidemia. In addition, C. auris, the frequency of which has increased in recent years, is a new factor that should be considered in candidemia cases.

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.

Epidemiology, clinical characteristics, outcome and biofilm forming properties in candidaemia: A single-centre retrospective 4-year analysis from Hungary.

BACKGROUND: Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm-related properties is limited. OBJECTIVE: This study evaluated the clinical characteristics of candidaemia, to assess the biofilm-forming properties of isolates, and to identify the risk factors of mortality. PATIENTS AND METHODS: A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1-day-old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30-day mortality rate. RESULTS: The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty-six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30-day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17-8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62-11.42, p = .004), and pneumonia (OR 0.261, 95% CI 0.1-0.67, p = .006). CONCLUSIONS: This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients.

Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital.

Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.

Among all fungemia episodes, hematological malignancies, immunosuppressive therapy, neutropenia, and preexposure to antifungals were risk factors for non-Candida yeast fungemia; diabetes mellitus, urinary catheters, and total parenteral nutrition were risks for candidemia.