Integrating omics techniques and culture-independent systems may improve the detection of persistent candidemia: data from an observational study.

INTRODUCTION: Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. METHODS: This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. RESULTS: 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00-1.00) when candidemia was defined according to both methods. CONCLUSION: Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

A privacy-preserving platform oriented medical healthcare and its application in identifying patients with candidemia.

Federated learning (FL) has emerged as a significant method for developing machine learning models across multiple devices without centralized data collection. Candidemia, a critical but rare disease in ICUs, poses challenges in early detection and treatment. The goal of this study is to develop a privacy-preserving federated learning framework for predicting candidemia in ICU patients. This approach aims to enhance the accuracy of antifungal drug prescriptions and patient outcomes. This study involved the creation of four predictive FL models for candidemia using data from ICU patients across three hospitals in China. The models were designed to prioritize patient privacy while aggregating learnings across different sites. A unique ensemble feature selection strategy was implemented, combining the strengths of XGBoost's feature importance and statistical test p values. This strategy aimed to optimize the selection of relevant features for accurate predictions. The federated learning models demonstrated significant improvements over locally trained models, with a 9% increase in the area under the curve (AUC) and a 24% rise in true positive ratio (TPR). Notably, the FL models excelled in the combined TPR + TNR metric, which is critical for feature selection in candidemia prediction. The ensemble feature selection method proved more efficient than previous approaches, achieving comparable performance. The study successfully developed a set of federated learning models that significantly enhance the prediction of candidemia in ICU patients. By leveraging a novel feature selection method and maintaining patient privacy, the models provide a robust framework for improved clinical decision-making in the treatment of candidemia.

Clinical evaluation of the T2Candida assay for the rapid diagnosis of candidemia.

We evaluated the clinical performance of the T2Candida assay. The overall agreement of the T2Candida assay results with the blood culture results was 95.3 % (121/127). The T2Candida assay detected three Candida albicans/tropicalis-positive specimens and one Candida krusei/glabrata-positive specimen; however, it did not detect two Candida glabrata specimens.

Prediction of candidemia with machine learning techniques: state of the art.

In this narrative review, we discuss studies assessing the use of machine learning (ML) models for the early diagnosis of candidemia, focusing on employed models and the related implications. There are currently few studies evaluating ML techniques for the early diagnosis of candidemia as a prediction task based on clinical and laboratory features. The use of ML tools holds promise to provide highly accurate and real-time support to clinicians for relevant therapeutic decisions at the bedside of patients with suspected candidemia. However, further research is needed in terms of sample size, data quality, recognition of biases and interpretation of model outputs by clinicians to better understand if and how these techniques could be safely adopted in daily clinical practice.

Candida is a type of fungus that can cause fatal infections. To confirm the presence of the infection, doctors may search for the fungus in the blood. Here, we discuss if computer systems can help to identify infection more easily and more rapidly.

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.

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.

Rapid identification,fluconazole and micafungin susceptibility testing of Candida species from blood culture by a short incubation method.

This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.

Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Evaluation of Candidemia in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients have high rates of invasive fungal infections. Candida species are the most commonly isolated fungi. Our aim was to identify risk factors, clinical presentations, and outcomes of candidemia in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated adult (≥18 years old) transplant recipients seen from May 2011 to December 2022 at Baskent University Ankara Hospital. From medical records, we retrospectively reviewed age, sex, transplant type, candidemia agent, risk factors, concomitant infections, and mortality of patients with Candida detected in blood culture. We used SPSS statistics software (version 25) to analyze data. RESULTS: There were 1080 organ transplants performed during the study period (717 kidney, 279 liver, 84 heart). There were 855 who were ≥18 years (655 kidney, 127 liver, 73 heart), of whom candidemia was detected in 26 (16 male; 11 kidney, 11 liver, 4 heart) with a median age of 47.5 years. The most common agents were Candida albicans and Candida glabrata. The most common chronic diseases were hypertension, cirrhosis, and cardiomyopathy. Eighteen patients had a concomitant focus of infection. Ten patients had pneumonia accompanying candidemia. The 30-day mortality rate was as high as 53.8%. The mean duration of candidemia after transplant was 23 months. Catheter-related candidemia was observed in 65% of patients. The 30-day mortality was found to be significantly higher in patients followed in the intensive care unit (P = .014), receiving total parenteral nutrition (P = .001), using broad-spectrum antibiotics (P = .001), and having pneumonia (P = .042) accompanying candidemia. CONCLUSIONS: For adult solid-organ transplant recipients with candidemia, careful monitoring is essential for successful management of total parenteral nutrition, central catheter, use of broadspectrum antibiotics, and invasive interventions.

Bloodstream infection caused by Wickerhamiella pararugosa in a patient with intestinal obstruction: A case report.

The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4-8 and 0.06 µg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient.

Unresolved issues in the diagnosis of catheter related candidemia: A position paper / Cuestiones no resueltas en el diagnóstico de la candidemia relacionada con el catéter: un documento de opinión

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper. (AU)

La incidencia y las tendencias recientes de la candidemia y la contribución de la pandemia de COVID-19 a su evolución no están bien documentadas. El catéter es uno de los principales focos de infecciones por Candida spp., pero los métodos empleados para confirmar el origen de la candidemia siguen basándose en los datos generados para la infección bacteriana. La presencia de Candida spp. en la punta de un catéter retirado es el método de referencia para la confirmación, pero no siempre es posible proceder a dicha retirada. Los métodos conservadores, sin retirada del catéter, no han sido estudiados específicamente para microorganismos cuyos tiempos de crecimiento son diferentes a los de las bacterias y, por tanto, estos resultados no son aplicables a la candidemia. Las diferentes especies de Candida spp. no tienen un tropismo particular para la colonización del catéter y los biomarcadores fúngicos, aún no han podido contribuir a la determinación del origen de la candidemia. Técnicas como la resonancia magnética T2MR todavía no se ha empleado para este fin. Por último, todavía no existe un consenso sobre cómo proceder cuando se aísla Candida spp. en un catéter extraído y los hemocultivos obtenidos por venas periféricas simultáneas son negativos. Ante esta falta de datos firmes, un grupo de expertos ha formulado una serie de preguntas y ha tratado de responderlas en base a la literatura, indicando las carencias presentes y ofreciendo su propia opinión. Todos los autores están de acuerdo con las conclusiones del manuscrito y lo ofrecen como documento de posición y discusión. (AU)

Evaluation of the mannan antigen assay in neonates with or without Candida albicans colonization.

Mannan antigen (MA) in neonates as a marker of invasive candidemia is not well studied, although 4% of all neonatal intensive care unit admissions are attributed to Candida spp. infections. The aim of this case-control study was to evaluate the performance of MA (Platelia™ Candida AgPluskit, Bio-Rad) in neonates who had rectal Candida colonization or in non-colonized controls. We cultured 340 rectal swabs of neonates and MA was negative in 24/25 C. albicans colonized (96% specificity) and in 30/30 non-colonized neonates (100% specificity). The results indicate a high specificity of the assay, which could be useful in neonates with possible candidemia.

The present study aimed to evaluate the use of mannan antigen (MA) assay in a neonatal unit and compared between C. albicans colonized and non-colonized infants. According to our results, MA found to have high specificity in both groups.

Candida parapsilosis complex in the clinical setting.

Representatives of the Candida parapsilosis complex are important yeast species causing human infections, including candidaemia as one of the leading diseases. This complex comprises C. parapsilosis, Candida orthopsilosis and Candida metapsilosis, and causes a wide range of clinical presentations from colonization to superficial and disseminated infections with a high prevalence in preterm-born infants and the potential to cause outbreaks in hospital settings. Compared with other Candida species, the C. parapsilosis complex shows high minimal inhibitory concentrations for echinocandin drugs due to a naturally occurring FKS1 polymorphism. The emergence of clonal outbreaks of strains with resistance to commonly used antifungals, such as fluconazole, is causing concern. In this Review, we present the latest medical data covering epidemiology, diagnosis, resistance and current treatment approaches for the C. parapsilosis complex. We describe its main clinical manifestations in adults and children and highlight new treatment options. We compare the three sister species, examining key elements of microbiology and clinical characteristics, including the population at risk, disease manifestation and colonization status. Finally, we provide a comprehensive resource for clinicians and researchers focusing on Candida species infections and the C. parapsilosis complex, aiming to bridge the emerging translational knowledge and future therapeutic challenges associated with this human pathogen.

Lack of relationship between genotype and virulence in Candida species / Ausencia de relación entre el genotipo y la virulencia en especies de Candida

BACKGROUND: The virulence of isolates among different Candida species causing candidemia may play a role in the prognosis of the patients. Furthermore, the potential relationship between genotype and virulence is still unclear and need to be further studied. AIMS: We aim to assess the relationship between genotype and virulence in Candida species using a Galleria mellonella larvae infection model. METHODS: One hundred and ninety-four isolates from 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) were compared against the same number of each species singleton genotypes in terms of survival of G. mellonella larvae. RESULTS: The median of survival and the IQR ranges of clusters and singleton were as follows: C. albicans (2 days, IQR 1.5-2 vs. 2 days, IQR 1-2.25), C. parapsilosis (2 days, IQR 1.5-2.6 vs. 2 days, IQR 2-3.3), and C. tropicalis (1 day, IQR 1-3.5 vs. 2 days, IQR 2-3.5; p < 0.05). High intra-cluster variability in terms of median of survival was found regardless the species. CONCLUSIONS: No relationship between genotype and virulence in Candida was observed with the G. mellonella model

ANTECEDENTES: La virulencia de cepas de diferentes especies de Candida causantes de candidemia puede jugar un papel en el pronóstico de los pacientes, y su estudio en el modelo de infección en Galleria mellonella puede ser útil para entender su contribución general a la infección. Además, la potencial relación entre genotipo y virulencia requiere de más estudios. OBJETIVOS: Se evaluó la relación entre genotipo y virulencia en especies de Candida mediante el modelo de infección de larvas de G. mellonella. MÉTODOS: Se estudió la supervivencia de las larvas infectadas con 194 aislados incluidos en 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) y con el mismo número de aislados con genotipos únicos por especie. RESULTADOS: La mediana de supervivencia y los rangos intercuartílicos (IQR) de clusters y genotipos únicos se muestra a continuación: C. albicans (2 días, IQR: 1,5-2 vs. 2 días, IQR: 1-2,25), C. parapsilosis (2 días, IQR: 1,5-2,6 vs. 2 días, IQR: 2-3,3), y C. tropicalis (un día, IQR: 1-3,5 vs. 2 días, IQR: 2-3,5; p < 0,05). Encontramos una importante variabilidad en la mediana de supervivencia entre cepas del mismo cluster, independientemente de la especie analizada. CONCLUSIONES: No se encontró relación entre el genotipo y la virulencia entre los aislados de Candida evaluados mediante el modelo de infección de G. mellonella

Biomarkers of fungal infection: expert opinion on the current situation / Biomarcadores de infección fúngica: opinión de expertos sobre la situación actual

The introduction of non-culture-based diagnostic techniques is revolutionizing the world of microbiological diagnosis and infection assessment. Fungi are no exception, and the introduction of biomarkers has opened up enormous expectations for better management of these entities. Biomarkers are diverse, their targets are also diverse and their evaluation has been done preferably in an individualized use and with deficient designs. Less is known about the value of the combined use of biomarkers and the impact of the negativity of two or more biomarkers on antifungal treatment decisions has been poorly studied. Given the paucity of prospective, randomized and definitive studies, we have convened experts from different fields, with an interest in invasive fungal infections, to answer some questions about the current relevant use of fungal biomarkers. This document summarizes the answers of these experts to the different questions

La introducción de técnicas de diagnóstico no basadas en cultivo está revolucionando el mundo del diagnóstico microbiológico y de la aproximación a las infecciones. Los hongos no son una excepción, y la introducción de biomarcadores ha abierto enormes expectativas para una mejor manejo de estas enfermedades. Hay diversos biomarcadores cuyo significado es también diverso pero su evaluación se ha hecho preferentemente en un uso individual y con estudios con distintos diseños. Se sabe menos sobre el valor de la combinación de biomarcadores y el impacto de la negatividad de dos o más de los mismos en las decisiones de tratamiento antifúngico ha sido poco estudiado. Dada la escasez de datos prospectivos, en estudios aleatorizados y definitivos, hemos convocado a expertos de diferentes campos con un interés en las infecciones micóticas invasivas, para responder a algunas preguntas sobre el uso actual y relevante de los biomarcadores fúngicos. Este documento resume las respuestas del grupo de expertos a las preguntas que se les formularon sobre el tema

Isolation of Candida in the blood cultures of patients admitted to the Emergency Room in a tertiary care hospital / Aislamiento de Candida en hemocultivos de pacientes ingresados en el Servicio de Urgencias de un hospital de tercer nivel

Background: In Spain, data of candidemia are limited to surveys conducted in specific areas or tertiary care centers. Also, in recent years, attention has shifted toward episodes of candidemia in non-ICU wards. Aims: We reviewed the cases of Candida isolates recovered from the blood of patients admitted to the Emergency Room (ER) in our tertiary care hospital. Methods: The patients selected for this study had an isolation of Candida in the blood culture. All data were collected retrospectively from the clinical records of a 11-year period. Results: Candida albicans and other species of the genus were present in 10 and 18 patients, respectively. The patients did not present different clinical features in comparison with other reports of hospitalized patients. All patients had several risk factors for candidemia. Only two patients had received previous antifungal therapy before admission. All the isolates of C. albicans, Candida glabrata and the only isolate of Candida tropicalis were susceptible to all the antifungal agents tested. Only one isolate of Candida parapsilosis was susceptible dose-dependent to fluconazole, and the only isolate of Candida metapsilosis was resistant to fluconazole. Conclusions: It is essential to evaluate the risk factors, underlying conditions and clinical features in non-hospitalized patients in order to determine whether an empirical treatment for candidemia is appropriate

Antecedentes: En España, los datos sobre candidemia están limitados a áreas específicas u hospitales de tercer nivel. En los últimos años el foco de atención sobre esta infección se ha desplazado a áreas de pacientes que no son críticos. Objetivos: Se revisaron los aislamientos de Candida obtenidos de hemocultivos de pacientes que ingresaron en el Servicio de Urgencias de nuestro hospital de tercer nivel. Métodos: Los pacientes se seleccionaron por presentar un aislamiento de Candida en hemocultivo. Todos los datos fueron recogidos retrospectivamente de las historias clínicas de los pacientes atendidos en un período de 11 años. Resultados: Candida albicans y otras especies del género se aislaron en 10 y 18 pacientes, respectivamente. Las características clínicas de los pacientes no mostraban diferencias en comparación con los datos publicados en la bibliografía sobre pacientes hospitalizados. Todos los pacientes presentaban factores de riesgo para desarrollar candidemia. Únicamente dos pacientes habían recibido tratamiento antimicótico antes del ingreso. Todas los aislamientos de C. albicans,Candida glabrata y el único de Candida tropicalis fueron sensibles a todos los antimicóticos probados. Solo un aislamiento de Candida parapsilosis fue sensible al fluconazol en función de la dosis y el único aislamiento de Candida metapsilosis fue resistente al fluconazol. Conclusiones: Es fundamental evaluar los factores de riesgo, las enfermedades de base y otras características clínicas de los pacientes no hospitalizados con el fin de establecer la instauración de un tratamiento empírico para la candidemia

Factores de riesgo y letalidad asociados a candidemia neonatal en una unidad de neonatología / Risk factors and lethality associated with neonatal candidemia in a neonatal unit

OBJETIVO: Determinar los principales factores de riesgo asociados a candidemia en neonatos. PACIENTES Y MÉTODO: Se realizó un estudio de casos y controles retrospectivo pareado, desde enero de 2014 a diciembre de 2016. Los casos fueron pacientes con aislamiento en hemocultivo y/o líquido cefalorraquídeo de Candida spp. luego de sus primeras 48 horas intrahospitalarias y los controles fueron neonatos escogidos del censo estadístico de la sala de neonatología pareados según su fecha de admisión a sala (rango de 30 días), peso al nacer, edad gestacional y condición de egreso (vivo o fallecido). Por cada caso seleccionamos dos controles. Los factores de riesgo evaluados fueron la estancia intrahospitalaria mayor a 7 días, el uso de antibióticos de amplio espectro, ventilación mecánica, nutrición parenteral mayor a 5 días, procedimientos invasivos como colocación de accesos venosos centrales y cirugías abdominales y torácicas, enterocolitis necrosante y crecimiento de microorganismo bacteriano en hemocultivo previo a la candidemia. RESULTADOS: Durante el período de estudio hubo aislamiento de Candida spp. en 141 neonatos. Se encontró que el 49% fue de Candida parapsilosis con la mayor letalidad asociada. En el análisis multivariado se identificaron como factores de riesgo la estancia intrahospitalaria mayor a 7 días (OR = 17,0, 95% IC = 2,36-122,4), uso de líneas umbilicales (OR = 9,04, 95% IC = 1,55-52,5), exposición a cirugía (OR = 12,4, 95% IC = 1,76-87,3) y el uso de meropenem (OR = 4,62, 95% IC = 1,34-15,9). CONCLUSIÓN: La estancia intrahospitalaria prolongada mayor a 7 días y la exposición a cirugía fueron los factores de riesgo más importantes en este estudio para el desarrollo de candidemia neonatal.

OBJECTIVE: To identify the main risk factors associated with neonatal candidemia. PATIENTS AND METHOD: A retrospective paired case-control study was conducted from January 2014 to December 2016. The cases were patients with isolation in blood culture and/or cerebrospinal fluid of Candida spp. after their first 48 hours in the hospital and the controls cases were neonates chosen from the statistical census of neonatology paired according to their admission date (30-day range), birth weight, gestational age, and discharge condition (alive or deceased). For each case, we select two controls. The risk factors evaluated were intrahospital stay over seven days, use of broad-spectrum antibiotics, mechanical ventilation, parenteral nutrition longer than five days, invasive procedures such as central venous access and abdominal and thoracic surgeries, necrotizing enterocolitis and growth of bacterial microorganisms in blood culture before candidemia. RESULTS: During the study period, 141 patients developed candidemia. 49% of the cases corresponded to Candida parapsilosis with the highest associated lethality rate. The multivariate analysis identified as risk factors hospital stay longer than seven days (OR = 17.0, 95% CI = 2.36-122.4), use of umbilical lines (OR = 9.04, 95% CI = 1.55-52.5), abdominal and/or thoracic surgery (OR = 12.4, 95% CI = 1.76-87.3), and treatment with Meropenem (OR = 4.62, 95% CI = 1.34-15.9). CONCLUSION: Prolonged intrahospital stay longer than seven days and thoracic and/or abdominal surgery were the most significant risk factors in this study for the development of neonatal candidemia.

Candidemia y colonización por Candida auris, un reto diagnóstico / Candidemia and colonization by Candida auris, a diagnostic challenge

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Identificación molecular y sensibilidad a los antifúngicos de aislamientos de sangre del complejo Candida parapsilosis en Venezuela / Molecular identification and in vitro antifungal susceptibility of blood isolates of the Candida parapsilosis species complex in Venezuela

Antecedentes. Candida parapsilosis constituye un complejo de especies formado por Candida parapsilosis sensu stricto, Candida orthopsilosis y Candida metapsilosis. Estudios a nivel mundial han descrito su epidemiología y sensibilidad a los antifúngicos. Objetivos. Los objetivos de este trabajo fueron identificar molecularmente aislamientos de sangre del complejo Candida parapsilosis y determinar su sensibilidad in vitro a los antifúngicos de uso sistémico. Métodos. Se estudiaron 86 aislamientos del complejo C. parapsilosis, provenientes de la Red de Vigilancia de Candidemia del Departamento de Micología del Instituto Nacional de Higiene Rafael Rangel, recogidos en el periodo 2008-2011. Se realizó la amplificación del gen de la deshidrogenasa alcohólica secundaria por reacción en cadena de la polimerasa y los productos fueron analizados mediante los polimorfismos de la longitud de sus fragmentos de restricción, mediante el uso de la enzima BanI. Las pruebas de sensibilidad se realizaron mediante Etest® según las instrucciones del fabricante, con modificaciones. Resultados. De los 86 aislamientos estudiados, 81 (94,2%) fueron C. parapsilosis sensu stricto, 4 (4,6%) C. orthopsilosis y uno (1,2%) C. metapsilosis. C. parapsilosis fue sensible a la anfotericina B y la caspofungina, y su porcentaje de resistencia al fluconazol y el voriconazol fue bajo. C. orthopsilosis y C. metapsilosis fueron sensibles a todos los antifúngicos probados. Conclusiones. Los resultados aportaron por primera vez en Venezuela información importante sobre la distribución del complejo C. parapsilosis en casos de candidemia, y apoyan la necesidad de continuar con los programas de vigilancia, incluyendo la discriminación molecular de las especies y las pruebas de sensibilidad a los antifúngicos, que permitirán orientar la terapia específica (AU)

Background. Candida parapsilosis is a species complex consisting of Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis. Studies worldwide have described its epidemiology and susceptibility to antifungal agents. Aims. The aims of this study were to carry out the molecular identification of blood isolates belonging to the Candida parapsilosis species complex, and to determine their in vitro susceptibility to antifungals of systemic use. Methods. A study of 86 strains of C. parapsilosis species complex collected in 2008-2011 and obtained from the Candidaemia Surveillance Network of Mycology Department of the Rafael Rangel National Institute of Hygiene, was made. Secondary alcohol-dehydrogenase gene amplification was performed using polymerase chain reaction, and the products were analysed by restriction fragments length polymorphisms using the enzyme BanI. Susceptibility tests were performed using Etest®, following the manufacturer's instructions with modifications. Results. Of the 86 isolates studied, 81 (94.2%) were C. parapsilosis sensu stricto, 4 (4.6%) C. orthopsilosis, and one (1.2%) C. metapsilosis. C. parapsilosis isolates were susceptible to amphotericin B and caspofungin, showing low rates of resistance to fluconazole and voriconazole. C. orthopsilosis and C. metapsilosis were susceptible to all the antifungals tested. Conclusions. The results obtained in Venezuela provide for the first time important information about the distribution of C. parapsilosis species complex in cases of candidaemia, and support the need for continuing surveillance programs, including molecular discrimination of species and antifungal susceptibility tests, which may guide specific therapy (AU)