Candida Bloodstream Infections Research Articles

Deep learning-based characterization of neutrophil activation phenotypes in ex vivo human Candida blood infections

Early identification of human pathogens is crucial for the effective treatment of bloodstream infections to prevent sepsis. Since pathogens that are present in small numbers are usually difficult to detect directly, we hypothesize that the behavior of the immune cells that are present in large numbers may provide indirect evidence about the causative pathogen of the infection. We previously applied time-lapse microscopy to observe that neutrophils isolated from human whole-blood samples, which had been infected with the human-pathogenic fungus Candida albicans or C. glabrata, indeed exhibited a characteristic morphodynamic behavior. Tracking the neutrophil movement and shape dynamics over time, combined with machine learning approach, the accuracy for the differentiation between the two Candida species was about 75%. In this study, the focus is on improving the classification accuracy of the Candida species using advanced deep learning methods. We implemented (i) gated recurrent unit (GRU) networks and transformer-based networks for video data, and (ii) convolutional neural networks (CNNs) for individual frames of the time-lapse microscopy data. While the GRU and transformer-based approaches yielded promising results with 96% and 100% accuracy, respectively, the classification based on videos proved to be very time-consuming and required several hours. In contrast, the CNN model for individual microscopy frames yielded results within minutes, and, utilizing a majority-vote technique, achieved 100% accuracy both in identifying the pathogen-free blood samples and in distinguishing between the Candida species. The applied CNN demonstrates the potential for automatically differentiating bloodstream Candida infections with high accuracy and efficiency. We further analysed the results of the CNN using explainable artificial intelligence (XAI) techniques to understand the critical features and patterns, thereby shedding light on potential key morphodynamic characteristics of neutrophils in response to different Candida species. This approach could provide new insights into host-pathogen interactions and may facilitate the development of rapid, automated diagnostic tools for differentiating fungal species in blood samples.

Chip-Based Molecular Evaluation of a DNA Extraction Protocol for Candida Species from Positive Blood Cultures.

The diagnosis of Candida bloodstream infection (BSI) may rely on a PCR-based analysis of a positive blood culture (PBC) obtained from the patient at the time of BSI. In this study, a yeast DNA extraction protocol for use on PBCs was developed and evaluated with the molecular mouse (MM) yeast blood (YBL) chip-based PCR assay, which allowed us to detect nine medically relevant Candida species. We studied 125 simulated or clinical PBCs for Candida species. A positive correlation between the DNA concentration and colony-forming unit count was found for simulated (Spearman's ρ = 0.58; p < 0.0001) and clinical (Spearman's ρ = 0.23, p = 0.09) PBCs. The extracted DNA yielded positive results with the MM YBL chip assay that agreed with the Candida species-level identification results for 63 (100%) of 63 isolates from simulated PBCs and 66 (99.5%) of 67 isolates from clinical PBCs. The false-negative result was for one C. tropicalis isolate that grew together with C. albicans in PBC. None of the 30 (Candida)-negative clinical BCs included as negative controls yielded a positive result with the MM YBL chip assay. Our DNA extraction protocol for the Candida species couples efficiency and simplicity together. Nevertheless, further studies are needed before it can be adopted for use with the MM YBL chip assay.

2883. Comparative outcomes following Candida bloodstream infections in patients with left ventricular assist devices (LVAD)

Abstract Background Left ventricular assist devices (LVAD) are an important management strategy for end-stage heart failure, however they carry a risk of infection. This study examines attributable outcomes of LVAD presence in patients presenting with Candida bloodstream infection (Candidemia). Methods 1233 patients with candidemia admitted to Barnes Jewish Hospital between January 2010-December 2021 were retrospectively included, of whom 39 had an LVAD at the time of infection. Demographics, comorbidities, microbiologic data, and risk factors for infection were analyzed. Outcome measures included 30 and 90-day mortality, need for mechanical ventilation, and dialysis. Risk factors for candidemia, and outcomes following infection were compared between patients with and without LVAD presence. Results Candidemic patients in the LVAD cohort were more likely to be male (77%) compared to the non-LVAD group (54%) (Table 1). Patients with an LVAD were more likely to have central venous access (p-value 0.04), and to have received extracorporeal membrane oxygenation (ECMO) prior to infection (67% vs 46%, p-value=0.01). There were no statistically significant differences in rates of parenteral nutrition, abdominal surgeries, liver disease or malignancies between the two cohorts. C. parapsilosis was the most common causative species in patients with LVAD (38% in LVAD group vs 16%) followed by C. albicans compared to the non-LVAD cohort (24% in LVAD group vs 39%). Patients in both groups had similar rates of mechanical ventilation, and hemodialysis need. HeartMate2 was the most common LVAD strategy in 21 patients (54%). Two patients required LVAD exchange as part of treatment. Presence of an LVAD did not significantly impact 30-day (31% in LVAD group vs 35%, p-value=0.62) or 90-day mortality (38% in LVAD group vs 41%, p-value 0.77). Within the LVAD cohort, 90-day mortality was associated with a shorter time duration from LVAD placement to candidemia. Conclusion In patients presenting with Candidemia, presence of an LVAD did not impact 30 or 90-day mortality. A shorter time from LVAD placement to infection was associated with poorer outcomes. Disclosures All Authors: No reported disclosures

Predictors of outcomes in patients with candidemia in an Intensive Care Unit

Objective: Candidemia is a life-threatening infection that causes high mortality rates in intensive care units (ICUs). This study aims to&#x0D; evaluate predictors of the outcome of patients with candidemia in ICU.&#x0D; Patients and Methods: This observational, retrospective study included patients with Candida bloodstream infection (BSI) in ICUs&#x0D; between 6 years of the episode. A binary logistic regression analysis was conducted to inspect the association with mortality.&#x0D; Results: The median age of 74 patients was 68.5, and 53.8% were men. C. parapsilosis was the most frequently isolated fungal species.&#x0D; The 30-day mortality rate was 50%. In the logistic regression model the Acute Physiology and Chronic Health Evaluation (APACHE)&#x0D; II score, positive blood culture on the seventh day, inotropes needed on the day of blood culture positivity, and ventilator-associated&#x0D; pneumonia (VAP) were significant risk factors for the outcome of patients. There was no difference in mortality between an early start&#x0D; of antifungal treatment or central venous catheter removal time.&#x0D; Conclusion: A shift to C. parapsilosis is observed in this study. Host-related factors such as APACHE II score, need for mechanical&#x0D; ventilation or need for inotropes affect mortality more than early treatment and source control in patients with Candida BSI.

The evaluation of Candida-related central line-related bloodstream infections in pediatric cancer patients: A pre- and post-intervention study.

The purpose of this study was to assess the efficacy of a central line maintenance bundle in preventing catheter-related (implanted venous access devices, port) Candida bloodstream infections. The study encompassed two distinct time periods, namely, pre-bundle and bundle. The number of catheter-related bloodstream infections (CRBSI) episodes per catheter days for each timeframe was determined. Upon implementation of the central line bundle, the rate of CRBSI reduced significantly from 4.27 per 1000 central line days in the pre-bundle period to 1.0 per 1000 central line days in the bundle period (p < .001). Using a central line bundle to avoid CRBSIs in pediatric cancer patients with ports led to a significant decrease in Candida species-related CRBSIs.

Epidemiological Characteristics, Antifungal Susceptibility, Risk Factors, and Outcomes of Candida Bloodstream Infection: A Ten-Year Surveillance in a Teaching Hospital in China.

Candida is one of the most important pathogens of hospital-acquired bloodstream infections. Its morbidity and mortality are still high, which is a serious global public problem. To investigate the strain distribution, drug susceptibility, clinical characteristics of patients, and risk factors affecting the prognosis of Candida bloodstream infection (BSI). We retrospectively collected the clinical data, infection-related indicators, prognosis, strain prevalence and drug susceptibility of 163 patients with Candida BSI in a teaching hospital from January 2012 to December 2022. Univariate and multivariate logistic regression were used to analyze the risk factors affecting the prognosis. In 163 cases of Candida BSI, Candida albicans accounted for 48.47%, and Candida non-albicans accounted for 51.53%. A total of 163 patients with Candida BSI were mainly distributed in intensive care unit (ICU) and emergency department, accounting for 40.49% and 14.72%, respectively. The resistance rate of Candida albicans to fluconazole, itraconazole and voriconazole was less than 10%, and the sensitivity rate of Candida tropicalis to fluconazole, itraconazole and voriconazole was less than 80%. The mortality rate of 163 patients with Candida BSI was 33.13%, with Candida non-albicans higher than that of Candida albicans (p = 0.04). Multivariate analysis showed that hemodialysis (OR = 0.199, 95% CI: 0.059-0.673, P = 0.009), arteriovenous catheters (OR = 0.344, 95% CI: 0.130-0.913, P = 0.032), elevated neutrophil count (OR = 0.409, 95% CI: 0.194-0.862, P = 0.019) and APACHE II score (OR = 0.848, 95% CI: 0.789~0.911, P < 0.001) were independent risk factors for death in patients with candidemia. The blood flow infection rate of Candida non-albicans is increasing, and the mortality rate and resistance to antifungal drugs are higher than that of Candida albicans. Hemodialysis, arteriovenous catheters, elevated neutrophil count and APACHE II score were associated with death in patients with Candida BSI.

Epidemiology and Outcomes of Non-albicans Candida Bloodstream Infections in Transplant Recipients and Cancer Patients.

We performed a retrospective survey of non-Candida albicans candidemia in patients with cancer, including those with solid tumors and those with hematological malignancies as well as transplants patients both, solid-organ transplant recipients and hematopoietic stem cell transplant recipients. The study was performed at two healthcare centers in New York City and covered the years 2018-2022. A total of 292 patients (318 isolates) were included in the study. In order of frequency, C. glabrata (38%) was the most common species recovered, followed byC. parapsilosis(19.2%), C. tropicalis(12.6%),C. krusei(10.7%),C. lusitaniae(5.7%),andC. guilliermondii(4.4%). Micafungin was the most common antifungal treatment and 18.5% of patients were on antifungal prophylaxis. The 30-day crude mortality was 40%. 4.5% of patients had more than one non-albicans species detected. In conclusion, this study represents one of the largest surveys of non-albicans species in cancer and transplant patients and provides data on the current epidemiology of these Candida species in this patient population.

Candidemia - Species Distribution and Antifungal Resistance Patterns in Two Tertiary Care Centers in South India

Background: Bloodstream infections due to Candida species are a significant cause of morbidity and mortality in hospitalized patients worldwide. Epidemiology of Candidemia is dynamic with reports of non-albicans Candida species on a steady increase and the emergence of C.auris reported from many centers in India. This study was undertaken to analyze species distribution and antifungal susceptibility of Candida bloodstream infections in two tertiary care centers in Telangana, South India. Material and Methods: In a retrospective analysis, Candida isolates from blood cultures of patients with suspected bloodstream infection over five years (2017-2021) were identified and tested for antifungal susceptibility by Vitek 2 Compact (Biomerieux, France). Results: A total of 85,603 blood cultures were processed from two centers from January 2017 to December 2021. Among these, 270 (0.31%) Candida species were isolated. Of the total Candida isolates, C. tropicalis (49.2%) was the most common isolate, followed by C. albicans 55 (20.3%), C. glabrata 35 (12.9%), C. parapsilosis 25 (9.2%), C. auris (5.5%), C. guilliermondii (1.4%) and C. krusei (1.1%). We have tested six antifungals and of the total isolates, resistance to fluconazole was highest (11.9%) followed by amphotericin B (7.0%), caspofungin (2.9%), voriconazole (2.3%), flucytosine (1.8%) and micafungin (0.7%). C.auris isolates were found to be resistant to two or three classes of antifungals tested and 13.3% were pandrug -resistant. Conclusion: C.tropicalis was the most common isolate and each Candida species showed varied antifungal resistance rates. We emphasize the need for the identification of Candida species and antifungal susceptibility for every invasive isolate to tailor targeted preventive and therapeutic antifungal strategies in line with current evidence and guidelines.

Candida Bloodstream Infection and Antifungal Susceptibility Over Three Years in a Single Center from Medinah, Saudi Arabia

In the healthcare setting, Candida bloodstream infections significantly increase morbidity and mortality. There is little proof that invasive infections in Saudi Arabia are brought on by Candida spp. To identify Candida species that cause bloodstream infections and ascertain the clinical outcome and risk factors for mortality in a Saudi Arabian tertiary hospital. This retrospective analysis covered all instances in which patients hospitalized to Ohud hospital, a tertiary care facility in Madinah, Saudi Arabia, between January 2019 and December 2021, had positive blood cultures for Candida. Anaerobic and aerobic Bactec bottles were inoculated with blood samples and then incubated at 35°C for five days. Identification-YST card kits from VITEK II (BioMerieux, France) for yeast and yeast-like organisms. Testing for antifungal susceptibility was done using AST YS07. A total of 78 patients (71% men, 29% women) were found to have candidemia. Candida albicans (51.3%), Candida parapsilosis (16.7%), and Candida tropicalis (16.7%) were the three Candida spp. that were most frequently isolated. Those with Saudi (51%; P = 0.500), leukopenia (40%; P = 0.001), neutrophilia (92%; P = 0.638), and thrombocytopenia (42%; P = 0.374) had a higher incidence of candidemia. Fluconazole sensitivity in non-albicans Candida species was 39.5%. Nonetheless, caspofungin was effective against all species. This study discovered an epidemiological shift toward more non-albicans Candida spp. in Saudi Arabia as well as a changing pattern in the Candida spp. causing bloodstream infections.

T2Candida assay: diagnostic performance and impact on antifungal prescribing.

To assess the performance of T2Candida for the diagnosis of invasive candidiasis (IC) against gold standards of candidaemia or consensus IC definitions, and to evaluate the impact of T2Candida on antifungal drug prescribing. A retrospective review was undertaken of all T2Candida (T2MR technology, T2 Biosystems) performed from October 2020 to February 2022. T2Candida performance was evaluated against confirmed candidaemia or against proven/probable IC within 48 hours of T2Candida, and its impact on antifungal drug prescriptions. T2Candida was performed in 61 patients, with 6 (9.8%) positive results. Diagnostic performance of T2Candida against candidaemia had a specificity of 85.7% and negative predictive value (NPV) of 96.8%. When comparing T2Candida results with consensus definitions of IC, the specificity and NPV of T2Candida was respectively 90% (54/60) and 98.2% (54/55) for proven IC, and 91.4% (53/58) and 96.4% (53/55) for proven/probable IC. Antifungals were initiated in three of six patients (50%) with a positive T2Candida result. Thirty-three patients were receiving empirical antifungals at the time of T2Candida testing, and a negative result prompted cessation of antifungals in 11 (33%) patients, compared with 6 (25%) antifungal prescriptions stopped following negative beta-d-glucan (BDG) testing in a control population (n = 24). T2Candida shows high specificity and NPV compared with evidence of Candida bloodstream infection or consensus definitions for invasive Candida infection, and may play an adjunctive role as a stewardship tool to limit unnecessary antifungal prescriptions.

Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study)

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0-93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.

Candida bloodstream infection among children hospitalised in three public-sector hospitals in the Metro West region of Cape Town, South Africa

BackgroundCandida bloodstream infection (BSI) causes appreciable mortality in neonates and children. There are few studies describing the epidemiology of Candida BSI in children living in sub-Saharan Africa.MethodsA retrospective descriptive study was conducted at three public sector hospitals in Cape Town, South Africa. Demographic and clinical details, antifungal management and patient outcome data were obtained by medical record review. Candida species distribution and antifungal susceptibility testing results were obtained from the National Health Laboratory Service database.ResultsOf the 97 Candida BSI episodes identified during a five-year period, 48/97 (49%) were Candida albicans (C. albicans), and 49/97 (51%) were non-C. albicans species. The overall incidence risk was 0.8 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children’s Hospital. Of the 77/97 (79%) Candida BSI episodes with available clinical information, the median age (interquartile range) at the time of BSI was 7 (1–25) months, 36/77 (47%) were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22/77 (29%) study participants. Most of the Candida BSI episodes were healthcare-associated infections, 63/77 (82%). Fluconazole resistance was documented among 17%, 0% and 0% of C. parapsilosis, C. tropicalis and C. albicans isolates, respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of Candida BSI diagnosis was 13/75 (17%). On multivariable analysis, factors associated with mortality within 30 days of Candida BSI diagnosis included vasopressor therapy requirement during Candida BSI, adjusted Odds ratio (aOR) 53 (95% confidence interval 2–1029); hepatic dysfunction, aOR 13 (95% CI 1–146); and concomitant bacterial BSI, aOR 10 (95% CI 2–60).ConclusionThe study adds to the limited number of studies describing paediatric Candida BSI in sub-Saharan Africa. Non-C. Albicans BSI episodes occurred more frequently than C. albicans episodes, and vasopressor therapy requirement, hepatic dysfunction and concomitant bacterial BSI were associated with an increase in 30-day mortality.

Candida bloodstream infection in patients with cancer: A retrospective analysis of an 11-year period

BackgroundCandida bloodstream infection (CBSI) is a growing problem among patients with cancer. AimTo describe the main clinical and microbiological characteristics in patients with cancer who suffer CBSI. MethodsWe reviewed the clinical and microbiological characteristics of all patients with CBSI diagnosed between January 2010 and December 2020, at a tertiary-care oncological hospital. Analysis was done according to the Candida species found. Multivariate logistic regression analysis was used to determine the risk factors associated with 30-day mortality. ResultsThere were 147 CBSIs diagnosed, 78 (53%) in patients with hematologic malignancies. The main Candida species identified were Candida albicans (n=54), Candida glabrata (n=40) and Candida tropicalis (n=29). C. tropicalis had been mainly isolated from patients with hematologic malignancies (79.3%) who had received chemotherapy recently (82.8%), and in patients with severe neutropenia (79.3%). Seventy-five (51%) patients died within the first 30 days, and the multivariate analysis showed the following risk factors: severe neutropenia, a Karnofsky Performance Scale score under 70, septic shock, and not receiving appropriate antifungal treatment. ConclusionsPatients with cancer who develop CBSI had a high mortality related with factors associated with their malignancy. Starting an empirical antifungal therapy the soonest is essential to increase the survival in these patients.

Candida Lusitaniae Endophthalmitis: A Brief Literature Review with a Focus on Treatment Options

Intraocular fungal infections are uncommon. They may originate either exogenously, as occurs with penetrating trauma and postoperative infections, or endogenously, through hematogenous spread. Patients at the highest risk of endogenous endophthalmitis are those with central venous catheters, total parenteral nutrition, and active intravenous drug use, as well as those who are immunosuppressed [1]. Candida species are the most common fungi identified from endogenous sources related to the above. Although the incidence of ocular involvement is unclear, a few studies provide a range of 2.2–16% in patients with candidemia [2,3]. Non-albicans species of candida infections are very rare. In particular, C. lusitaniae is found in only approximately 1% of patients with candida blood stream infections [4]. Treating candida ophthalmologic infections usually requires expertise of both ophthalmology and infectious diseases. Patients who have evidence of only chorioretinitis should be treated with systemic antifungal agents. Intravitreal injection in combination with systemic antifungals is recommended for patients with infections involving the macula or vitreous humor. Vitrectomy along with intravitreal injection and systemic antibiotic therapy is needed for patients with heavy vitritis [5]. The duration of treatment is decided on a case-by-case basis but typically consists of four to six weeks of systemic antifungal therapy.

201. Utility of Incorporation of Beta-D-glucan Testing in Algorithms for Diagnosis and Treatment of Candidemia.

Abstract Background Candidemia is a common hospital acquired infection that is associated with significant morbidity and mortality. The optimal strategy for diagnosis remains unknown. Methods We evaluated 2 distinct diagnostic strategies in hospitalized patients with suspicion of Candida bloodstream infection, namely strategy #1 that included simultaneous blood cultures and T2Candida and strategy #2 that included blood cultures, T2Candida testing and Beta-D-glucan (BDG). We examined the consistency with which each diagnostic algorithm led to changes in antifungal prescribing, the overall rate of antifungal utilization and patients’ clinical outcomes. Flow Chart. Figure 1. Results Among 96 patients tested with strategy #1, 3 had a positive result. Of those 100% completed a 14-day antifungal course for candidemia or were on antifungals until hospital discharge. Of the 29 out 120 patients that tested positive with strategy #2, 55.2% received a complete 14-day course or were on antifungals until hospital discharge. The percentage of completed treatment increased to 75.0% and 80.0% when the threshold for BDG positivity was increased at 200 pg/ml and 500 pg/ml respectively. We observed a significant difference in the overall antifungal utilization with 268.5 days of antifungals per 1,000 patient days for strategy #1, as opposed to 371.9 days of antifungals for strategy #2, a 38.5% increase. Negative tests at both diagnostic strategies led to a similar rate of antifungal discontinuation 3 days after testing (36.8% and 37.0% for strategy #1 and #2 respectively). We did not find significant benefits in death and/or subsequent diagnosis of candidemia between the 2 diagnostic strategies. Sensitivity analyses performed based on indication for testing and severity of illness did not significantly alter results. Table 1.Characteristics of patients tested for suspicion of candidemia with the 2 diagnostic strategies. Figure 2. Duration of antifungal therapy among patients with positive BDG at different thresholds A. BDG&amp;lt;80 pg/ml, B. BDG&amp;lt;200 pg/ml, C. BDG&amp;lt;500 pg/ml. Figure 3. Percentage of patients who were taken off antifungals within 3 days of testing for different BDG thresholds, BDG&amp;lt;80 pg/ml, BDG&amp;lt;200 pg/ml, and BDG&amp;lt;500 pg/ml. Conclusion In summary, the addition of BDG in diagnostic algorithms for candidemia was interpreted variably by clinicians, was associated with a significant increase in antifungal utilization, and it did not appear to lead to measured clinical benefits for patients. Diagnostic strategies of common and serious infections that incorporate non-culture diagnostics need to be evaluated for added benefit. Table 2.Antifungal utilization among patients tested for suspicion of candidemia with the 2 diagnostic strategies. Table 3. Outcomes among patients tested for suspicion of candidemia with the two different diagnostic strategies. Disclosures All Authors: No reported disclosures.

Short Course of Antifungal Therapy in Patients With Uncomplicated Candida Bloodstream Infection: Another Case of Less Is More in the Clinical Setting?

The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5-11 days) or PC (12-24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7-11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14-16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31-1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20-5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35-1.50; P = .38) did not differ between groups. Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

Epidemiology, management and outcome of candidaemia in patients with diabetes.

Candidaemia is the commonest fungal bloodstream infection in hospitalised patients. Diabetes is one of the risk factors for mortality from candidaemia. We compared the epidemiology, clinical characteristics and management of candidaemia in patients with and without diabetes. Over a 10-year period, 200 episodes of Candida bloodstream infection were documented. Patients with diabetes were younger (58.7 vs 65.5 years), less likely to be suffering from cancer (21.8% vs 36%), and had significantly lower 30-day and 90-day crude mortality (17.2% vs 35.6% and 28.4% vs 48.6%, respectively). Candida glabrata was more common in patients with diabetes (39.3% vs 29.7%). Based on European Confederation of Medical Mycology (ECMM) quality indicators, the management of patients with and without diabetes was similar. Our study highlights the importance of epidemiological data in relation to candidaemia in patients with diabetes and the growing threat of invasive C. glabrata infection in this subset of patients.

Population Pharmacokinetic Model and Optimal Sampling Strategies for Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.

Candida bloodstream infections are associated with high attributable mortality, where early initiation of adequate antifungal therapy is important to increase survival in critically ill patients. The exposure variability of micafungin, a first-line agent used for the treatment of invasive candidiasis, in critically ill patients is significant, potentially resulting in underexposure in a substantial portion of these patients. The objective of this study was to develop a population pharmacokinetic model including appropriate sampling strategies for assessing micafungin drug exposure in critically ill patients to support adequate area under the concentration-time curve (AUC) determination. A two-compartment pharmacokinetic model was developed using data from intensive care unit (ICU) patients (n = 19), with the following parameters: total body clearance (CL), volume of distribution of the central compartment (V1), inter-compartmental clearance (CL12), and volume of distribution of the peripheral compartment (V2). The final model was evaluated with bootstrap analysis and the goodness-of-fit plots for the population and individual predicted micafungin plasma concentrations. Optimal sampling strategies (with sampling every hour, 24 h per day) were developed with 1- and 2-point sampling schemes. Final model parameters (±SD) were: CL = 1.03 (0.37) (L/h/1.85 m2), V1 = 0.17 (0.07) (L/kg LBMc), CL12 = 1.80 (4.07) (L/h/1.85 m2), and V2 = 0.12 (0.06) (L/kg LBMc). Sampling strategies with acceptable accuracy and precision were developed to determine the micafungin AUC. The developed model with optimal sampling procedures provides the opportunity to achieve quick optimization of the micafungin exposure from a single blood sample using Bayesian software and may be helpful in guiding early dose decision-making.

Pediatric Candida Bloodstream Infections Complicated with Mixed and Subsequent Bacteremia: The Clinical Characteristics and Impacts on Outcomes.

Background: Pediatricians face a therapeutic challenge when patients with Candida bloodstream infections (BSIs) simultaneously have positive bacterial culture. We aim to characterize the clinical characteristics of pediatric Candida BSIs complicated with mixed bacteremia and subsequent bacterial infections, risk factors and impacts on outcomes. Methods: All episodes of pediatric Candida BSIs between 2005 and 2020 from a medical center in Taiwan were reviewed. Mixed Candida/bacterial BSIs were defined as isolation of a bacterial pathogen from blood cultures obtained within 48 h before or after the onset of Candida BSI. The clinical features and impacts of mixed Candida/bacterial BSIs were investigated. Results: During the study period, 320 patients with a total of 365 episodes of Candida BSIs were identified and analyzed. Mixed Candida/bacterial BSIs were 35 episodes (9.6%). No significant difference was found between mixed Candida/bacterial BSIs and monomicrobial Candida BSIs in terms of patient demographics, Candida species distributions, most chronic comorbidities or risk factors. Patients with mixed Candida/bacterial BSIs were associated with a significantly higher risk of subsequent bacteremia (51.4% vs. 21.2%, p &lt; 0.001) and a relatively higher candidemia-attributable mortality rate (37.2% vs. 22.4%, p = 0.061) than those with monomicrobial Candida BSIs. Mixed Candida/bacterial BSIs were not an independent risk factor of treatment failure or final mortality according to multivariate logistic regression analyses. Conclusions: The clinical significance of mixed Candida/bacterial BSIs in children included a longer duration of septic symptoms, significantly higher likelihood to have subsequent bacteremia, and relatively higher risk of candidemia attributable mortality.

A longitudinal study of Candida bloodstream infections in a Japanese university hospital: species distribution, drug susceptibility, clinical features, and mortality predictors.

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.