Invasive candidiasis in a Brazilian neonatal intensive care unit / Candidíase invasiva em uma Unidade de Terapia Intensiva Neonatal brasileira

Abstract Objectives: to describe the epidemiology of invasive candidiasis in a neonatal intensive care unit. Methods: cross-sectional study that included all neonates with invasive candidiasis confirmed by blood culture from April 2015 to June 2018. Demographic, clinical and microbiological data were analyzed, comparing neonates with extreme low birth weight (ELBW) with neonates ≥ 1000g birth weight, considering a p <0.05 as statistically significant. Results: there were 38 cases of invasive candidiasis, resulting in an overall incidence of 2.5%. Twelve (32%) were ELBW neonates and 26 (68%) neonates ≥ 1000g birth weight, an incidence of 4.4% and 2.0%, respectively. Abdominal surgery was more frequent among neonates with birth weight ≥ 1000g compared to ELBW neonates (85% vs. 17%; p <0.01), as well as the median in days of antibiotics use (18 vs. 10.5; p = 0.04). The median in days of mechanical ventilation was more frequent among ELBW neonates (10 vs. 5.5; p = 0.04). The majority of Candida species were non-albicans (64%). Fatality rate was 32%. Conclusions: the incidence of invasive candidiasis among neonates with birth weight ≥ 1000g was higher than that found in the literature. This group has a higher proportion of gastrointestinal malformations that require surgery. Thus, fluconazole prophylaxis may be necessary for a broader group of neonates.

Resumo Objetivos: descrever a epidemiologia de candidíase invasiva em uma unidade de terapia intensiva neonatal. Métodos: estudo transversal que incluiu todos recém-nascidos com candidíase invasiva confirmada por hemocultura de abril de 2015 a junho de 2018. Foi analisado dados demográficos, clínicos e microbiológicos, comparando recém-nascidos de extremo baixo peso ao nascer (EBPN) com os recém-nascidos com peso ao nascer ≥1000g, considerando um valor de p<0,05 como estatisticamente significativo. Resultados: houve 38 casos de candidíase invasiva, resultando em uma incidência global de 2,5%. Doze (32%) eram neonatos de EBPN e 26 (68%) neonatos com peso ao nascer ≥1000g, resultando em uma incidência de 4,4% e 2,0%, respectivamente. A realização de cirurgia abdominal foi mais frequente nos neonatos com peso ao nascer ≥1000g em comparação com os neonatos de EBPN (85% vs. 17%; p<0,01), assim como a mediana dos dias de uso de antibióticos (18 vs. 10,5; p =0,04). Já o a mediana dos dias de ventilação mecânica foi mais frequente entre recém-nascido de EBPN (10 vs. 5,5; p = 0,04). A maioria das espécies de Candida eram não-albicans (64%). A letalidade foi de 32%. Conclusões: a incidência de candidíase invasiva entre os recém-nascidos ≥1000g ao nascer foi superior ao encontrado na literatura. Este grupo tem uma maior proporção de malformações gastrointestinais que requerem cirurgia. Assim, a profilaxia com fluconazol pode ser necessária para um grupo mais amplo de recém-nascidos.

Incidencia y etiología de la candidiasis invasiva en la Unidad de Cuidados Intensivos de Niños del Centro Hospitalario Pereira Rossell / Incidence and etiology of invasive candidiasis in the Pediatric Intensive Care Unit of of the Pereira Rossell Hospital Center

Introducción: en los últimos años ha aumentado la incidencia de candidiasis invasiva (CI) a nivel mundial. En nuestro país no se disponen de estudios epidemiológicos sobre CI. El objetivo fue determinar incidencia de CI en la Unidad de Cuidados Intensivos de Niños del Centro Hospitalario Pereira Rossell. Metodología: estudio descriptivo retrospectivo. Se incluyeron los niños con CI hospitalizados entre 1/1/2009-1/6/2014. A partir de los cultivos micológicos se identificaron las historias clínicas de los pacientes que desarrollaron CI. Se definió CI al aislamiento de Candida en algún sitio estéril. Se calcularon la densidad de incidencia y de prevalencia. Se registró motivo de ingreso y presencia de factores de riesgo para CI. Resultados: se identificaron 6 casos de CI, incidencia de 1,86 c/1000 ingresos. Los aislamientos se realizaron en hemocultivos (n=3) y líquido peritoneal (n=3). Las especies de Candida aisladas fueron C. albicans (n=3), C. parapsilosis (n=2) y C. tropicalis (n=1). Los factores de riesgo para CI presentes fueron dispositivos invasivos (n=6), antibióticos de amplio espectro (n=6), alimentación parenteral (n=5), cirugía abdominal(n=4). Todos los aislamientos fueron sensibles a los azoles. En 1 de las 6 CI se inició tratamiento empírico previo al aislamiento. Fallecieron 4 de los 6 pacientes. Discusión: la incidencia fue similar a otra experiencia realizada en cuidados intensivos pediátricos. Los pacientes que desarrollaron CI presentaron asociación de factores de riesgo. Los aislamientos fueron sensibles a fluconazol. Caracterizar a estos niños permitirá iniciar en forma oportuna el tratamiento antifúngico. Se destaca la importancia de desarrollar la vigilancia continua sobre las especies de Candida y su patrón de sensibilidad a los antifúngicos.

Introduction: invasive infections by Candida strains have increased around the world in the last years. There are no epidemiological studies on invasive candidiasis (IC) in Uruguay. The study aimed to find out the incidence of IC in the Pediatric Intensive Care Unit (PICU) at the Pereira Rossell Hospital Center (CHPR). Method: a retrospective and descriptive study was conducted. Children hospitalized in PICU of the CHPR between 1/1/2009 and 1/6/2014 were included in the study. The medical records of patients who developed IC were identified based on mycological cultures. Invasive candidiasis was defined as the isolation of the fungus in a sterile site. Incidence and prevalence density were calculated. Cause for hospitalization and risk factors for IC were recorded. Results: six cases of IC were identified and the incidence was of 1.86/1000 hospitalized children in PICU. Isolation of Candida was done in blood cultures (n=3) and peritoneal fluid (n=3). The species of Candida isolated were C. albicans (n=3), C.parapsilosis (n=2) and C. tropicalis (n=1). Risk factors for IC were identified in the 6 cases. Use of invasive prosthesis and a wide spectrum antibiotics were identified in the 6 cases, as well as parenteral nutrition (n=5) and abdominal surgery (n=4). All isolations of Candida were sensitive to fluconazole. Antifungal empiric treatment was started in one case prior to the isolation of Candida. Four out of six children died. Discussion: the incidence of IC found was similar to that in another study in a PICU. Children who developed IC presented several risk factors for IC. The 6 isolations of Candida were sensitive to fluconazole. Analyzing the clinical features of these children will allow the identification of patients with high risk of IC and to timely initiate antifungal treatment. It is necessary to maintain a continuous surveillance on Candida species and their sensitivity pattern to antifungal medication.

Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients

Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Paraná state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2%) and the majority of isolates from GenBank (71.4%). The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated.

Candidiasis invasoras en el paciente crítico adulto / Invasive candidiasis in critically ill adult patient

Las infecciones invasoras por Candida spp, representan una patología relevante en los pacientes críticos. Para su oportuno diagnóstico es necesaria una elevada sospecha clinica, tomando en consideración el cuadro clinico y la presencia de factores de riesgo. Pese a la incorporación de nuevos fármacos al arsenal terapéutico durante la última década, mantiene una elevada mortalidad. Las claves para mejorar los desenlaces clínicos en estos pacientes son el empleo de una terapia precoz, eficaz y que permita la cobertura de distintas especies de Candida: C albicans y no albicans. Recientes guías internacionales sugieren la terapia empírica con equinocandinas ante la sospecha de candidiasis invasora en esta población de pacientes. Este grupo de fármacos ha documentado adecuada eficacia clínica y seguridad en estos pacientes. Se espera que la incorporación de nuevas equinocandinas al mercado aminore sus costos y mejore el acceso a este grupo de fármacos.

Invasive infections by Candida strains are a relevant pathology in critically ill patients. Candida should be considered where a high risk of infection is present for a critical early diagnosis. Despite the incorporation of new drugs in the therapeutic armamentarium over the last decade, mortality remains high. The key in improving clinical outcomes of these patients are the use of early effective therapies that offer coverage against different strains of Candida: C. albicans and non-albicans. Recent international guidelines suggest empiric therapy with echinocandins in suspected invasive candidiasis in this patient population. This group of drugs adequately documented clinical efficacy and safe use in these patients. The emergence of new echinocandins could improve access to these drugs by reducing their cost.