Episodes Of Candidemia Research Articles

Performance of a Real-Time PCR Assay for the Detection of Five Candida Species in Blood Samples from ICU Patients at Risk of Candidemia

The gold standard for diagnosing invasive candidiasis still relies on blood cultures, which are inefficient and time-consuming to analyze. We developed an in-house qPCR assay to identify the 5 major Candida species in 78 peripheral blood (PB) samples from ICU patients at risk of candidemia. Blood cultures and (1,3)-β-D-glucan (BDG) testing were performed concurrently to evaluate the performance of the qPCR. The qPCR was positive for DNA samples from all 20 patients with proven candidemia (positive PB cultures), showing complete concordance with Candida species identification in blood cultures, except for detection of dual candidemia in 4 patients, which was missed by blood cultures. Additionally, the qPCR detected Candida species in six DNA samples from patients with positive central venous catheters blood (CB) but negative PB cultures. BDG values were similarly high in these six samples and the ones with proven candidemia, strongly suggesting the diagnosis of a true candidemia episode despite the negative PB cultures. Samples from patients neither infected nor colonized yielded negative results in both the qPCR and BDG testing. Our qPCR assay was at least as sensitive as blood cultures, but with a shorter turnaround time. Furthermore, negative results from the qPCR provided strong evidence for the absence of candidemia caused by the five major Candida species.

Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections

BackgroundInvasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time.MethodsRetrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome.ResultsTwenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment.Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674).ConclusionsIn this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

Time-to-positivity in bloodstream infection for Candida species as a prognostic marker for mortality.

Time-to-positivity (TTP) may assist in predicting outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014-2015). Time to positivity was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12) and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 (95%CI 1.06-1.69). Shorter TTP was associated with increased mortality, with 1 day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%-46%) and 5-day TTP 11% (2/18) (95%CI: 2%-36%).

Ophthalmologic Examination and Echocardiography Should be the Essential Components of Candidemia Bundle.

Candidemia is the most common form of invasive candidiasis, and it is associated with end-organ involvement, prolonged hospitalization, increased mortality, and higher healthcare costs. Candidemia can lead to metastatic heart and ocular infections. This study aimed to define the incidence, characteristics, and mortality of candidemia episodes and compare the data with our center's previous results. In this single-center retrospective observational study, we enrolled 250 patients over 18 years diagnosed with candidemia between January 2015 and December 2020. We obtained patients' demographic, clinical, laboratory, and therapeutic data from medical records. An ophthalmologic examination and screening with echocardiography were carried out within the first week after candidemia diagnosis. There were 275 candidemia episodes from 250 patients. The incidence of candidemia was 2.8/1000 admissions and 5.68/ 10,000 inpatient days, higher than our previous results (1.23/1000 and 3.29/10,000). The median age was 65 (interquartile range [IQR]=52-75) years. Malignancies were the most frequent comorbidity (50%). The most common type was Candida albicans (n=115, 41.8%). Candida glabrata (n=61, 22.2%) was common, particularly in surgical patients, patients with malignancy, and critically ill patients. There was Infectious disease consultation in 93.3% (257) episodes.The ophthalmoscopic examination was made in 145 episodes (52.7%), and ophthalmitis was detected in 16 (11.0%). Echocardiography was performed in 139 (50.5%) episodes; one case had an endocarditis diagnosis. The 30-day mortality was 44.7% (n=123). Mortality rates in C. glabrata and Candida krusei infections were higher (54.1% and 66.7). The factors related to mortality were intensive care unit requirement (p=0.0001), chronic liver disease (p=0.005), corticosteroid usage (p=0.0001), previous antibiotic usage (p=0.013), multiple antibiotic usage ( p=0.020), and CVC related candidemia (p=0.010). Because of the life-threatening complications such as endocarditis, increased mortality rates, and higher healthcare costs, systematic and comprehensive candidemia bundle applications would be effective strategies for providing an effective antifungal stewardship program.

Risk factors and outcomes of fungal superinfections in patients with severe COVID-19: an observational study from Pisa academic hospital.

Superinfections acquired during the hospital course represent common complications in COVID-19 patients. Several studies reported an increasing incidence of COVID-19 associated pulmonary aspergillosis (CAPA) and candidaemia. The aim of this study is to describe fungal superinfections in a large cohort of hospitalized patients with COVID-19 and identify factors independently associated with the risk of fungal superinfections. Observational study including patients with COVID-19 admitted to the tertiary-care, University Hospital of Pisa, Italy from April 2020 to May 2021. Patients with pneumonia and laboratory confirmed SARS-CoV-2 infection with a RT-PCR test on a nasopharyngeal swab, were eligible for the study. Patients who died within 24 hours from admission and those with missing data were excluded. Data about fungal superinfections were collected. To identify factors independently associated with the development of fungal superinfections, a multivariate regression analysis was performed. Among 983 patients with COVID-19, 52 (5.3%) fungal superinfections were detected. Fungal superinfections included: 24/52 (46%) CAPA, 27/52 (51.9%) episodes of candidaemia and 1 case of pulmonary pneumocystosis in a haematological patient. All patients with CAPA were cared for in intensive care unit (ICU). The majority of patients received liposomal amphotericin B as antifungal treatment (83.3%). In-hospital mortality was 41.7%. Among 27 episodes of candidaemia, 16 (59.3%) occurred in ICU while 11 (40.7%) in medical wards. In-hospital mortality was 14.8%. Overall, patients with fungal superinfections had a median age of 73 (IQRs 59-77) years and a median length of ICU stay of 40 (17-50) days. In-hospital mortality among all patients with superinfections was 28.8%. On multivariable analysis, ICU stay (OR 17.63, 95% CI 8.3-37.41, p<0.001), high-dose steroids (OR 13.48, 95% CI 6.68-27.26, p<0.001), and diabetes mellitus (OR 2.14, 95% CI 1.09-4.17, p=0.026) were factors independently associated with the risk of developing a fungal superinfection. Fungal superinfections may complicate the hospital course of COVID-19 patients, especially of those admitted to ICU. Surveillance with detection of galactomannan on bronchoalveolar lavage in patients with clinical deterioration should be performed. A rational use of steroids is essential to avoid the risk of developing a fungal superinfection.

Validation of an Automated System for the Extraction of a Wide Dataset for Clinical Studies Aimed at Improving the Early Diagnosis of Candidemia

There is increasing interest in assessing whether machine learning (ML) techniques could further improve the early diagnosis of candidemia among patients with a consistent clinical picture. The objective of the present study is to validate the accuracy of a system for the automated extraction from a hospital laboratory software of a large number of features from candidemia and/or bacteremia episodes as the first phase of the AUTO-CAND project. The manual validation was performed on a representative and randomly extracted subset of episodes of candidemia and/or bacteremia. The manual validation of the random extraction of 381 episodes of candidemia and/or bacteremia, with automated organization in structured features of laboratory and microbiological data resulted in ≥99% correct extractions (with confidence interval < ±1%) for all variables. The final automatically extracted dataset consisted of 1338 episodes of candidemia (8%), 14,112 episodes of bacteremia (90%), and 302 episodes of mixed candidemia/bacteremia (2%). The final dataset will serve to assess the performance of different ML models for the early diagnosis of candidemia in the second phase of the AUTO-CAND project.

Epidemiology and associated risk factors for candidemia in a Canadian tertiary paediatric hospital: An 11-year review.

Candidemia represents a significant cause of morbidity and mortality in children. We examined the epidemiology and associated risk factors of candidemia at a Canadian tertiary care paediatric hospital over an 11-year period. A retrospective chart review was conducted on children with positive blood culture for Candida species between January 1, 2007 and December 31, 2018. Patient demographics, previously described candidemia risk factors, Candida species, follow-up investigations, interventions, and outcome data were included in the analysis. Sixty-one candidemia episodes were reported with an overall incidence rate of 5.1 cases per 10,000 patient admissions. Of the 66 species identified, the most common was Candida albicans (53%, 35), followed by Candida parapsilosis (18%, 12), and Candida glabrata (8%, 5). Mixed candidemia was noted in 8% (5/61) of episodes. The most common risk factors included presence of central venous catheter (95%, 58/61) and receipt of antibiotics in the last 30 days (92%, 56/61). Majority of patients received abdominal imaging (89%, 54/61), ophthalmology consult (84%, 51/61), and echocardiogram (70%, 43/61), regardless of age. Line removal was performed in 81% (47/58) of cases. Evidence of disseminated fungal disease on abdominal imaging was observed in 11% (6/54) of patients, all in non-neonates but with risk factors including immunosuppression and gastrointestinal abnormalities. The overall 30-day case fatality rate was 8% (5/61). C. albicans was the most commonly isolated species. Disseminated candidiasis was demonstrated mainly on abdominal imaging in patients with relevant risk factors, including immunosuppression and gastrointestinal abnormalities.

High Incidence of Candidemia in Critically Ill COVID-19 Patients Supported by Veno-Venous Extracorporeal Membrane Oxygenation: A Retrospective Study.

The incidence of candidemia in severe COVID-19 patients (0.8-14%) is two- to ten-fold higher than in non-COVID-19 patients. This retrospective analysis aimed to analyse the incidence of bloodstream infections (BSI) due to Candida in a cohort of COVID-19 patients supported with ECMO. Among 138 intubated and ventilated patients hospitalized for ≥10 days in the intensive care unit of a teaching hospital, 45 (32.6%) patients received ECMO support, while 93 patients (67.4%) did not meet ECMO criteria and were considered the control group. In the ECMO group, 16 episodes of candidaemia were observed, while only 13 in patients of the control group (36.0% vs. 14.0%, p-value 0.004). It was confirmed at the survival analysis (SHR: 2.86, 95% CI: 1.39-5.88) and at the multivariable analyses (aSHR: 3.91, 95% CI: 1.73-8.86). A higher candida score seemed to increase the hazard for candidemia occurrence (aSHR: 3.04, 95% CI: 2.09-4.42), while vasopressor therapy was negatively associated with the outcome (aSHR: 0.15, 95% CI: 0.05-0.43). This study confirms that the incidence of candidemia was significantly higher in critically ill COVID-19 patients supported with VV-ECMO than in critically ill COVID patients who did not meet criteria for VV-ECMO.

471. Comparison of Outcomes for Obese and Non-Obese Patients Receiving Micafungin 100 mg Daily for Candidemia

Abstract Background Echinocandins, such as micafungin, are first-line agents for the treatment of candidemia. Researchers have questioned the adequacy of the standard 100 mg dose for all patients, as certain characteristics such as obesity can significantly alter the pharmacokinetics of this agent. Prior data have shown obese patients may be less likely to achieve the pharmacodynamic targets shown to be associated with clinical success. The purpose of this study is to compare clinical outcomes for obese and non-obese patients receiving standard dosing of micafungin. Methods This is a multi-center, retrospective study conducted at two large academic hospitals. All adults admitted with a positive blood culture for Candida spp. between January 1st 2017 and December 31st 2021 were reviewed for inclusion. Patients who received &amp;gt; 1 dose of micafungin were designated as either obese (BMI ≥ 30 kg/m2) or non-obese (BMI &amp;lt; 30 kg/m2). Patients who received combination antifungal therapy or had subsequent episodes of candidemia were excluded. Results One hundred and eighty-five of 248 patients were included. Fifty-six (30.3%) patients were obese and 129 (69.7%) were non-obese. Most were critically ill (55.1%), middle-aged (median 60 years), Hispanic or Latino (52.7%) and male (57.8%). Patients received micafungin 100 mg IV daily for a median of 6 (IQR 3-11.5) days. Obese patients had a higher Charlson Comorbidity Index of 4.5 (IQR 3-6.8) compared to 4 (IQR 2-6) in non-obese patients. Critically ill obese and non-obese patients had median Sequential Organ Failure Assessment scores of 10 (IQR 6.75-11.5) and 9 (IQR 4-12), respectively. Clinical and microbiologic failure at day 14 were numerically higher in obese patients ([44.6% vs 32.3%; p = 0.13] and [19.6% vs 10.1%; p = 0.10], respectively), while in-hospital and 30-day mortality were significantly higher in the obese population ([39.3% vs 22.5%; p = 0.03] and [44.6% vs 27.1%; p = 0.03], respectively). Conclusion Obese patients treated for candidemia with micafungin 100 mg IV daily had a significantly higher in-hospital and 30-day mortality. Clinical and microbiological failure followed a similar trend, without meeting statistical significance. Additional studies are warranted to determine whether higher doses of micafungin may improve outcomes in obese patients. Disclosures All Authors: No reported disclosures.

1412. Racial Differences in Candidemic Patients at a Southern California Teaching Hospital

Abstract Background Racial disparities in diagnosis and management of infectious diseases in the US healthcare system have been reported. Candidemia is a leading healthcare associated bloodstream infection and is associated with significant mortality. Further, global rates of azole-resistant C. parapsilosis have dramatically increased. Nonetheless, literature describing racial and ethnic differences among candidemic patients is limited. The objective of this study was to describe infection characteristics and outcomes among non-Hispanic White (n-REM) and racially and ethnically minoritized (REM) patients with candidemia. Methods Adult patients hospitalized with ≥ 1 positive blood culture growing Candida between 1/2020 and 12/2021 were included. Based on documented race and ethnicity, patients were dichotomized into the n-REM or REM group. Pertinent data was collected and then compared between groups using univariate analysis. Significance was defined as P ≤0.05. Results 86 unique episodes of candidemia were included. REM patients were significantly younger (mean age 54 vs 62 years; P = 0.017) and had more risk factors for candidemia (median 4 vs 3). REM patients were also more likely to present with sepsis/septic shock (87% vs 81%) and require an ICU stay (57% vs 53%). Time to detection of candidemia was shorter in the REM group (median 38.5 vs 43 hours); however, time to initiation of active antifungal therapy was longer (median 48 vs 44 hours). Additionally, hospital LOS was longer in the REM group (median 25.5 vs 19.5 days). Central line infection was the most common source of candidemia. Despite similar documented sources of infection, microbiological differences were noted. Candida glabrata was more often isolated in n-REM patients (50% vs 27%; P = 0.04), whereas C. parapsilosis was more often isolated in REM patients (17% vs 3%; P = 0.048). Conclusion Despite being younger, REM patients were at an increased risk for candidemia. Furthermore, C. parapsilosis, a globally growing species of concern due to azole resistance, was more frequently isolated among REM patients. Rapid detection and speciation of candidemia may be particularly important among REM patients to ensure early initiation of optimal therapy. Further research exploring racial differences among candidemic patients is needed. Disclosures All Authors: No reported disclosures.

476. Epidemiology and Outcomes of Candidemia in a Large Academic Medical Center

Abstract Background Candidemia is an important cause of morbidity and mortality. Fluconazole resistance is associated with increased mortality in candidemia and thus echinocandins are recommended as first line empiric therapy. To understand the current landscape of candidemia treatment, we evaluated the epidemiology and outcomes of candidemia at our medical center, with a focus on differences in traditional azole-susceptible and non-susceptible candida species. Methods This is a retrospective cohort study including unique episodes of candidemia from 7/2017 – 12/2021 in hospitalized adult patients. We characterized candidemia episodes by species, age, hospital-onset, hospital location and critical illness. We compared traditionally azole susceptible organisms (e.g. C.albicans, C. parapsilosis, C.tropicalis) to non-susceptible (e.g. C.krusei, C.glabrata) based on antibiogram (cut off &amp;gt;94% susceptible) with the primary outcome of 30-day mortality. Secondary outcomes were recurrent/persistent candidemia, 90-day mortality and length of stay. Comparisons were done with χ2 or Wilcoxon rank sum tests. Logistic regression was performed to determine if azole-nonsusceptible candidemia was associated with 30-day mortality. Results 404 candidemic episodes for 389 patients were identified, of which 72% were due to azole-susceptible Candida spp. and C.glabrata and C.krusei were 23% and 5%, respectively. Critically ill patients were more likely to have azole-non-susceptible Candida spp (59 vs. 48%, p=0.04). Overall 30-day mortality was 35%, and was similar between azole-susceptible and non-susceptible groups, with no difference in other outcomes (Table 1). After adjusting for age and hospital-onset, critically ill patients with azole-non-susceptible candidemia had odds ratio of 1.5 (95% CI 0.87 – 2.7 p=0.13) for 30-day mortality. Distribution of candida species and associated 30-day mortality are found in Table 2. Demographics and Outcome Distribution of most common Candida spp. in candidemia in critically ill (n=205) Conclusion We found similar 30-day mortality rates in azole-susceptible and non-susceptible candida species since echinocandin first-line empiric therapy was implemented in guidelines. The impact on critically ill and invasive infections, including ocular involvement, needs further evaluation. Disclosures All Authors: No reported disclosures.

481. Risk Factors and Clinical Outcomes of Candidemia Associated with Severe Coronavirus Disease 2019 (COVID-19)

Abstract Background COVID-19 can cause serious illness requiring multimodal treatment of the viral infection and its associated complications, including the potential for secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear. Methods A multi-center, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 to August 2021. Risk factors associated with candidemia and mortality were characterized using multivariate analyses. Results A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 patients with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of all patients received biologic for COVID-19. In-hospital mortality was significantly higher in the case group compared to the control group (68% vs 40%, P &amp;lt; 0.01). Multivariable logistic regression revealed that the use of central lines, biologic and paralytic therapy were independent risk factors for candidemia. The presence of candidemia, older age, central line use, and intensive care unit admission were significantly associated with mortality. Demographics and Baseline Characteristics of Study Patients with SARS-CoV-2 Positive With or Without Candidemia Hospitalization Details and Outcomes Conclusion Clinicians should be aware of the possibility of development of candidemia in hospitalized older patients with severe COVID-19 and should closely monitor those patients at risk. Risk factors for developing candidemia in the setting of COVID-19 are largely consistent with classic risk factors previously identified. Disclosures Tanaya Bhowmick, MD, Gilead: Grant/Research Support|Shinogi: Advisor/Consultant Steven Smoke, PharmD, BCPS, BCIDP, Karius: Advisor/Consultant|Shionogi: Advisor/Consultant.

Epidemiology of Nosocomial Candidemia, Mortality, and Antifungal Resistance: 7-Year Experience in Turkey.

Candidemia is an important clinical condition that prolongs hospital stays and increases morbidity, mortality, and hospital costs. The aim of this retrospective study was to evaluate the epidemiological and microbiological characteristics of patients with candidemia between January 2013 and December 2019. Two hundred forty-one episodes of candidemia were observed in 230 patients, 45% of whom were female. The median age was 63 years, and 53.9% of the episodes were in the intensive care unit (ICU). Commonly observed predisposing factors for candidemia included antibiotic use (71.3%), urinary catheterization (56.3%), central venous catheter placement (50.3%), total parenteral nutrition (47.9%), solid-organ malignancy (46%), surgery (48.6%), chemotherapy (37%), and steroid treatment (25.5%). The crude mortality rate was 52.7%. A significant difference was found between survivors and non-survivors (P = 0.007) according to the Charlson Comorbidity Index. However, no statistically significant association was found between mortality and age, sex, surgical procedure, catheter-related candidemia, or Candida spp. infection. The most frequently isolated Candida sp. was C. albicans (51%). Overall resistance rates to fluconazole, voriconazole, caspofungin, micafungin, and flucytosine were 3.7%, 0%, 2.5%, 1.8%, and 1.8%, respectively. Consequently, there is a need for tests that provide higher success rates, rapid diagnosis of candidemia, and local epidemiological data on antifungal resistance.

Candida species associated with urinary tract infections

Around the world, candidemia is becoming more common. In the past thirty years, a number of factors, including the AIDS epidemic, an increase in the number of patients receiving immune-suppressive therapy for transplantation, and an increase in the use of antibiotics in hospital settings and even in the community, have changed the epidemiology of invasive fungal infections in general and candidemia in particular. Usage of broad-spectrum antibiotics, cancer treatment, Candida species colonization of mucosal surfaces and broad-spectrum use antifungal. Five species of the Candida genus are in charge of causing Urinary Tract Infections (UTIs): Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. The key to managing candidemia episodes is early diagnosis and appropriate therapy.

Fluconazole-resistant Candida parapsilosis: A new emerging threat in the fungi arena.

Candida parapsilosis is a leading cause of invasive candidiasis in southern Europe, Latin America and Asia. C. parapsilosis has been mostly considered susceptible to triazoles, but fluconazole resistance is on the rise in some countries. The main mechanism related to fluconazole resistance is the presence of ERG11p substitutions, dominated by the Y132F amino acid substitution. Isolates harbouring this substitution mimic C. auris given that they may cause hospital outbreaks, become endemic, and emerge simultaneously in distant areas around the world. At the moment, Spain is experiencing a brusque emergence of fluconazole resistance in C. parapsilosis; isolates harbouring the Y132F substitution were detected for the first time in 2019.A recent study on Candida spp isolates from blood cultures collected in 16 hospitals located in the Madrid metropolitan area (2019 to 2021) reported that fluconazole resistance in C. parapsilosis reached as high as 13.6%. Resistance rates rose significantly during those three years: 3.8% in 2019, 5.7% in 2020, and 29.1% in 2021; resistant isolates harboured either the dominant Y132F substitution (a single clone found in four hospitals) or G458S (another clone found in a fifth hospital). The COVID-19 pandemic may have increased the number of candidaemia cases. The reason for such an increase might be a consequence of uncontrolled intra-hospital patient-to-patient transmission in some hospitals, as an increase not only in C. parapsilosis candidaemia episodes but also in the spread of clonal fluconazole-resistant isolates might have occurred in other hospitals during the pandemic period. Patients affected with fluconazole-resistant C. parapsilosis harbouring the Y132F substitution presented a mortality rate ranging from 9% to 78%, were mainly admitted to intensive care wards but did not have differential risk factors compared to those infected by susceptible isolates. With scarce exceptions, few patients (≤20%) infected with fluconazole-resistant isolates had previously received fluconazole, thus supporting the fact that, although fluconazole might have been a key factor to promote resistance, the main driver promoting the spread of fluconazole-resistant isolates was patient-to-patient transmission.

Time to Positivity Facilitates an Early Differential Diagnosis of Candida tropicalis from Other Candida species.

BackgroundCandidemia caused by Candida tropicalis has more serious adverse consequences and an even higher mortality. Time to positivity (TTP) has been widely used to identify microbial species, resistant microorganisms and distinguish real pathogens and pollutants. However, few studies have demonstrated TTP as a presumptive diagnosis of C. tropicalis in patients with candidemia.Patients and MethodsA retrospective study of 136 episodes of candidemia and simulated blood cultures with 314 episodes of confirmed Candida strains were applied to explore the role of TTPs in diagnosing C. tropicalis. TTPs were recorded as the shorter one if both aerobic and anaerobic vials were positive. Lastly, relationships were tested between TTPs and resistance and initial inocula concentration.ResultsFor the retrospective study, the mean of TTPs for C. tropicalis from 136 patients with candidemia was significantly shorter than other Candida species. The area under the receiver operating characteristics (ROC) curve was 0.8896 ± 0.030 with a sensitivity of 92.86% and a specificity of 77.87%, respectively, indicating TTPs with a cut-off value of <25.50 h had a strong diagnostic power for C. tropicalis in patients with candidemia. Moreover, TTPs from 314 simulated blood cultures showed similar results as the retrospective study, demonstrating TTP is a powerful diagnostic tool in early diagnosing C. tropicalis in patients with candidemia. Additionally, our results showed no statistical significance between TTPs and initial inocula concentration and resistance of Candida species, suggesting initial inocula concentration does not impact TTPs, and TTPs may not be promising in predicting the resistance of all Candida species.ConclusionTTP can be employed to early distinguish C. tropicalis from other Candida species in patients with candidemia, which is extremely helpful to initiate empiric antifungal treatments to improve clinical outcomes.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BackgroundThe development of candidemia is a highly fatal condition in severe COVID‐19 infection.ObjectivesThis study aimed to develop a candidemia prediction score in COVID‐19 patient based on the patient's clinical characteristics, and healthcare‐related factors during intensive care units (ICU) follow‐up.Patients/MethodsSevere COVID‐19 patients hospitalised in ICU in Ankara City Hospital during the one‐year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score.ResultsOf 1305 COVID‐19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12–44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39–3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42–5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34–0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81–0.87).ConclusionWe developed and validated an easy‐to‐use clinical prediction score for candidemia in severe COVID‐19 infection. In COVID‐19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Clinical utility of time to positivity of blood cultures in cases of fungaemia: A prospective study

PurposeFungaemia due to yeast is a major cause of morbidity and mortality in critically ill patients. Although, automated blood cultures have improved the time to diagnosis, very few studies have systematically evaluated the utility of blood culture time to positivity (TTP) of fungaemia in the clinical scenario. In this study, we evaluated the TTP for different yeast species to determine its clinical utility. Material and methodsA prospective study including 244 consecutive patients admitted to the adult (n ​= ​76) and paediatric (n ​= ​168) intensive care units (ICUs) was conducted between December 2017 through March 2019. The clinical and demographic characteristics, BACTEC blood culture results and TTP for yeast positive blood cultures were recorded for analysis. ResultsA total of 244 patients with 357 episodes of candidaemia were enrolled during the study period. The TTP (mean ​± ​SD) for all yeast species was 26.8 ​± ​23.6 ​h while it was significantly longer in paediatric than adult patients (30.5 ± 24.7 vs. 25.2 ​± ​22.9 ​h; p ​= ​<0.0001). Wickerhamomyces anomalus and Cyberlindnera jadinii (previously C. utilis) were exclusively isolated from paediatric population where W. anomalus demonstrated significantly longer TTP than C. jadinii. Among adult cases, C. albicans exhibited significantly longer TTP than C. tropicalis. In paediatric cases, >80% of C. tropicalis and C. utilis flagged positive in blood culture before 24 ​h while majority (65.9%) of W. anomalus isolates flagged positive later than 24 ​h. Similarly in adult samples, 63% of C. tropicalis isolates beeped positive before 24 ​h. ConclusionTTP for yeast may provide insight regarding the responsible yeast species before final identification among critical patients with candidaemia. Larger studies are warranted for evaluating clinical utility of TTP considering other complex factors like yeast burden, generation time, virulence and host factors, which may affect TTP. Keywords: fungaemia; time to positivity; candidaemia; paediatric; adult.

P193 Candidemia in coronavirus disease 2019 patients in a university hospital in Buenos Aires, Argentina

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMIt is known that the incidence and epidemiology of candidemia vary according to different geographic regions and/or hosts. Between 1998 and 2019, the incidence in a university hospital in the city of Buenos Aires Argentina, ‘HCJSM’, was 2.19/1000 discharges. The coronavirus disease 2019 (COVID-19) pandemic altered the previously recognized course of severe infections, including candidemia.ObjectiveThe aim of this report is to determine the incidence of candidemia in critically ill COVID-19 patients, and the clinical and microbiological aspects of these episodes hospitalized at HCJSM.MethodsThe source documents of this retrospective study are medical records from patients with Sars-Cov-2 and candidemia who were diagnosed between March 1, 2020 and June 30, 2021. At the onset of the pandemic, the HCJSM began admitting patients with COVID-19, and elective procedures were canceled. Demographic, clinical, and laboratory data were reviewed. All data were analyzed using RStudio, a statistical computing platform (version 4.0.2).ResultsDuring the period under review, 61 episodes of candidemia were identified: 23 episodes (39.7%) in COVID-19 patients, and 38 episodes (60,3%) in no COVID-19 patients. Incidence (x 1000 admission) in no COVID-19 patients was 2.5 (38/14 903): in COVID-19 patients 14.4 (23/1595) and in COVID-19–ICU was 42.3 (20/472). The average age of patients is of 65 years (32-84 range years). The time from admission to ICU to the development of candidemia had a median of 18 days (RIC 9-23). A total of 87.5% of the patients had been on mechanical ventilation and 100% of the patients received broad-spectrum antibiotics and had catheters. Episodes were caused by C. parapsilosis (39.7%), C. albicans (35%), C. glabrata (14%), and other species of Candida (11%). A total of 62% of COVID-19 patients who developed episodes of candidemia died during the period under examination. The survival likelihood at 30 days of COVID-19 patients who developed candidemia was higher for C. parapsilosis episodes and lower for C. glabrata episodes.ConclusionThe incidence of candidemia showed an increase in COVID-19 hospitalized severe patients. The use of broad-spectrum antibiotics, the presence of catheters, and the use of ventilatory support in COVID-19 patients were the risk factors most associated with the development of candidemia. Although the number of episodes of candidemia is low, without the strength of statistical analysis, it is important to consider that the likelihood of survival of patients with episodes of candidemia varies according to the species recovered.

P399 Diagnostic value of Candida coloni zation index and serum Candida mannan antigen for candidemia in febrile episodes of pediatric lymphoreticular malignancies

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: To evaluate the diagnostic performance of Candida colonization index and serum Candida mannan antigen predicting candidemia in febrile episodes of pediatric lymphoreticular malignanciesMethodsIt was a prospective observational study done for 18 months, from November 2018 to April 2020 at the pediatric oncology unit of a multispecialty tertiary care center. Based on our patient load, duration of the proposed study, and available resources, a sample size of 49 (n = 49) was decided and 100 febrile episodes in children with lymphoreticular malignancy were studied. Children below 12 years, receiving chemotherapy for hematological malignancy having oral or axillary temperature ˃38.3°C for ˃1 h were included in this study. Children receiving the antifungal treatment in last 7 days were excluded from the study. Blood collected on day1 and day4 was cultured in BACTEC-9120. For colonization, swabs and samples were collected and cultured on SDA on day1, day4, and day8. All Candida isolates were subcultured on SDA and subjected to Gram's stain, germ tube test followed by Microscan identification. DNA sequencing followed by phylogenetic analysis was done for all the isolates of Candida recovered from blood. Antifungal susceptibility of yeast stains was done. Serum collected on day1 was used for C. mannan antigen detection using ELISA system.ResultsPrevalence of candidemia was 5%. Non-albicans Candida spp were isolated from blood cultures on day 4. Candida colonization decreased from day1 to day8. Colonization index (CI) day1 showed 80% sensitivity 98.9% specificity, and 98.9% negative predictive value. Significant colonization (CI ≥0.5) was seen in a larger proportion of cases that developed candidemia. There was a significant association of Candida colonization (CI ≥0.5) with occurrence of candidemia on day1 and day4. A total of 4 (80%) of candidemia episodes were positive for serum mannan antigen while 1 (20%) was negative. Mannan antigen was detected earlier with 80% sensitivity, 92.6% specificity, and 98.9% negative predictive value. All Candida isolates were sensitive to fluconazole, amphotericin-B, and caspofungin.Receiver operator characteristic curves for diagnostic performance of various parameters in predicting candidemia show the following trends:Best parameter in terms of AUROC is the CI (Day 1).Best parameters in terms of sensitivity are the CI (Day 1), CI (Day 4), and mannan antigen level.Best parameter in terms of specificity is the CI (Day 8).Best parameter in terms of positive predictive value is the CI (Day 1).Best parameters in terms of negative predictive value are the CI (Day 1), CI (Day 4), and mannan antigen level.Best parameters in terms of diagnostic accuracy are the CI (Day 1), CI (Day 8).ConclusionThe CI can predict candidemia but the threshold value needs to be explored in pediatric patients with lymphoreticular malignancies. Mannan antigen detection gives early results with a high negative predictive value.