Screening of susceptibility genes and an immunological study in a patient with recurrent cervical lymphadenitis caused by Candida albicans / 中华皮肤科杂志

Objective:To explore genetic etiology and evaluate antifungal immunity in a patient with recurrent cervical lymphadenitis caused by Candida albicans. Methods:Next-generation sequencing was performed to screen susceptibility genes for mycosis in a patient with recurrent cervical lymphadenitis caused by Candida albicans and his parents. Peripheral blood mononuclear cells (PBMCs) and neutrophils were extracted from the patient and 6 healthy controls, and subjected to in vitro co-culture with Candida albicans. Western blot analysis was performed to determine the expression of caspase recruitment domain-containing protein 9 (CARD9) in PBMCs of the patient, enzyme-linked immunosorbent assay to detect levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-17A, IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the co-culture medium, and a colony-counting method was used to detect the survival rate of Candida albicans after treatment with neutrophils. Statistical analysis was carried out by using t test for comparisons between two groups. Results:Two compound heterozygous mutations were identified in the CARD9 gene of the patient, including c.68C>A (p.S23X) in exon 2 inherited from his father and c.820dupG (p.D274Gfs*61) in exon 6 inherited from his mother. Western blot analysis showed that the relative expression level of CARD9 protein in the PBMCs was 0.41 ± 0.07 in the healthy control group, but CARD9 expression was absent in the patient. After stimulation with heat-inactivated Candida albicans spores, the levels of TNF-α, IL-6, IL-17A, IL-1β and GM-CSF secreted by PBMCs of the patient were significantly lower than those by PBMCs of the healthy controls (all P < 0.001). After 30- and 120-minute in vitro co-culture with neutrophils, the survival rates of Candida albicans were significantly higher in the patient (78.00%, 74.00%, respectively) than in the healthy controls (70.91% ± 1.75%, 34.55% ± 5.35%, t = 3.74, 6.99, respectively, both P < 0.05) . Conclusion:Compound heterozygous mutations were identified in the CARD9 gene of the patient with recurrent cervical lymphadenitis caused by Candida albicans, which led to the absence of CARD9 protein expression, and the patient had a defect in the immunity against Candida albicans.

Infección invasiva por Candida spp. En pacientes inmunocomprometidos: Descripción de curso clínico experiencia diagnóstica, manejo y seguimiento en centro de alta complejidad / Invasive infection by Candida spp. in immunocompromised patients: A description of clinical, diagnostics, therapeutic and follow up experience in high complexity healthcare center

Introducción: Candida spp. Es la principal causa de fungemia, cuya incidencia ha aumentado en los últimos años. Existen datos locales insuficientes sobre este tipo de infecciones. Materiales y métodos: Este fue un estudio observacional retrospectivo de 44 pacientes diagnosticados con candidiasis invasiva hospitalizados en la Fundación Valle del Lili, el cual es un centro de cuarto nivel afiliado a la Universidad Icesi en el Suroccidente Colombiano, entre los años 2012 a 2017. Resultados: Se identificaron 44 pacientes con candidiasis invasiva, 27 de ellos mujeres (61%). La mediana de edad fue de 56 años (36 - 70). Más del 50% tenían una enfermedad crónica subyacente, uso de antibióticos (84%), catéter venoso central (80%), ventilación mecánica (68%) y nutrición enteral (66%) El 80% requirió manejo en unidad de cuidados intensivos (UCI) donde debutaron con sepsis (68%) y falla respiratoria (61%). En el 90% de los casos se aisló alguna especie de Candida spp. A partir de hemocultivo y sólo al 22% se le realizó prueba de sensibilidad. El tratamiento de elección fue con fluconazol (80%), asociado a caspofungina (70%). La tasa de mortalidad fue del 49%, con una mediana de 33 (22-49,5) días desde el ingreso hasta el fallecimiento. C. albicans fue el principal microorganismo aislado. La resistencia a azoles en especies no albicans existe en nuestro medio. Conclusión: La candidiasis se presenta como candidemia asociada a infección bacteriana concomitante, que cobra mayor importancia en el contexto del paciente inmunosuprimido asociado a elevadas tasas de mortalidad.

Introduction: Candida spp. is the main cause of fungemia, whose incidence has increased in recent years. There are insufficient local data about this pathology. Materials and methods: This was an observational, retrospective chart review of 44 patients diagnosed with invasive candida who were hospitalized at Fundación Valle del Lili, which is a fourth level center affiliated to Icesi university between 2012 and 2017. Results: We identified 44 patients with invasive candidiasis, 27 of them women (61%). The median age was 56 years (36 - 70). More than 50% had an underlying chronic disease, use of antibiotics (84%), central venous catheter (80%), mechanical ventilation (68%) and enteral nutrition (66%). 80% required management in an intensive care unit. Sepsis (68%) and respiratory failure (61%) were the most common clinical presentation. Almost 90% of the cases, had positive blood cultures, but only 22% presented susceptibility tests. The treatment was mainly fluconazole (80%), associated with caspofungin (70%). The mortality rate was 49%, median of 33 (22-49.5) days from admission to death. Candida albicans was the main isolated organism. Azole resistance in non-albicans species was observed. Conclusion: Candidiasis presents as bacterial infection associated candidemia, which becomes more important in the context of the immunosuppressed patient with high mortality rates.

Candidemia en Colombia / Candidemia in Colombia

En Colombia, especialmente en las unidades de cuidados intensivos, la candidemia es una causa frecuente de infección del torrente sanguíneo y representa el 88 % de las infecciones fúngicas en pacientes hospitalizados, con una mortalidad entre 36 y 78 %. Su incidencia en Colombia es mayor a la reportada en los países desarrollados e, incluso, en otros países de Latinoamérica. Para su manejo deben considerarse los factores de riesgo del paciente, luego valorar las características clínicas y, finalmente, hacer los estudios microbiológicos y, si es necesario, pruebas moleculares. En general, las guías estadounidenses, latinoamericanas y europeas recomiendan las equinocandinas como el tratamiento de primera línea de la candidemia y difieren en el uso de fluconazol dependiendo de la 'evidencia', la gravedad de la enfermedad, la exposición previa a los azoles y la prevalencia de Candida no albicans. Dada su gran incidencia en nuestro país, asociada con una elevada mortalidad, esta infección debe buscarse sistemáticamente en pacientes con factores de riesgo, con el fin de iniciar oportunamente el tratamiento antifúngico.

In Colombia, especially in intensive care units, candidemia is a frequent cause of infection, accounting for 88% of fungal infections in hospitalized patients, with mortality ranging from 36% to 78%. Its incidence in Colombia is higher than that reported in developed countries and even higher than in other Latin American countries. First, the patient's risk factors should be considered, and then clinical characteristics should be assessed. Finally, microbiological studies are recommended and if the evidence supports its use, molecular testing. In general, American, Latin American, and European guides place the echinocandins as the first-line treatment for candidemia and differ in the use of fluconazole based on evidence, disease severity, previous exposure to azoles, and prevalence of Candida non-albicans. Taking into account the high incidence of this disease in our setting, it should be looked for in patients with risk factors to start a prompt empirical anti-fungal treatment.

Candidiasis invasiva en pacientes pediátricos ingresados / Invasive candidiasis in hospitalized pediatric patients

RESUMEN Introducción: la candidiasis es una infección fúngica causada principalmente por especies de candida no albicans que aparece generalmente en la piel o las membranas mucosas de los pacientes. Objetivos: caracterizar la incidencia de especies de candida con mayor número de aislamientos en los pacientes pediátricos hospitalizados, en el Hospital Mariana Grajales (Servicio de Neonatología) y Hospital José Luis Miranda, en el período 2013 - 2018, en Villa Clara. Métodos: estudio descriptivo y transversal con 50 aislamientos del género candida en hemocultivos de pacientes hospitalizados Hospital Mariana Grajales (Servicio de Neonatología) y Hospital José Luis Miranda (Servicio de Terapia Intensiva), Villa Clara, de enero 2013 - septiembre 2018. Se utilizó la estadística descriptiva e inferencial, mediante el test de Ji cuadrado de Pearson (x2) o el test exacto de Fisher a las variables: año de estudio, tipo de hospital, tipo de servicio y especie de candida aislada. Resultados: los mayores aislamientos de candidiasis invasiva correspondieron al pediátrico, en el servicio de Terapia Intensiva, 2018 (única con significación estadística).En esta misma unidad, el grupo de candida spp obtuvo el mayor índice, seguido de candida tropicalis, sin significaciones estadísticas. En el servicio de Neonatología el mayor número de aislamientos correspondió a candida spp, seguido de candida guillermondii, ambas sin significación estadística. Conclusiones: el servicio de Terapia Intensiva fue el que mayor número de casos de candidiasis invasiva y el año 2018 fue el más representativo. El grupo de candida spp fueron las especies que más se aislaron en ambos hospitales.

ABSTRACT Introduction: candidiasis is a fungal infection caused mainly by non-albicans Candida species that usually appears on the skin or mucous membranes of patients. Objective: to characterize the incidence of Candida species with the highest number of isolates in hospitalized pediatric patients, at Mariana Grajales Hospital (Neonatology Service) and José Luis Miranda Hospital, in the period 2013 - 2018, in Villa Clara. Methods: descriptive and cross-sectional study with 50 Candida genus isolates in blood cultures of patients hospitalized at Mariana Grajales Hospital (Neonatology Service) and José Luis Miranda Hospital (Intensive Care Service), Villa Clara, from January 2013 to September 2018. Descriptive and inferential statistics using Pearson's chi-squared test (χ2) or Fisher's exact test to the variables: year of study, type of hospital, type of service and isolated Candida species. Results: the largest isolates of invasive candidiasis corresponded to the Intensive Therapy service from the pediatric hospital in 2018 (only with statistical significance). In this same hospital, the Candida spp group obtained the highest index, followed by Candida tropicalis, without statistical significance. The largest number of isolates corresponded to Candida spp in the Neonatology service, followed by Candida guillermondii, both without statistical significance. Conclusions: the Intensive Therapy service was the one with the highest number of cases of invasive candidiasis and the year 2018 was the most representative. The group of Candida spp was the most isolated species in both hospitals.

Fatal necrotizing Candida esophagitis in a patient with leukocytoclastic cutaneous vasculitis and ankylosing spondylitis

Esophageal infection by Candida spp. is a common opportunistic entity in immunocompromised hosts; however, systemic fungal dissemination due to perforation or transmural necrosis, also known as necrotizing Candida esophagitis (NCE), is rare. We report the case of a 61-year-old male patient with diagnosed ankylosing spondylitis, severe arteriosclerosis, and vasculitis under immunosuppressive therapy who presented NCE with fungal and bacterial septicemia diagnosed at autopsy. Necrotizing esophagitis is a rare manifestation of Candida infection, which may be a final complication in severely ill patients. Unfortunately, it may be underdiagnosed, and we call attention to this devastating complication in patients with leukocytoclastic cutaneous vasculitis and ankylosing spondylitis.

Retrospective analysis of 76 neonates with invasive fungal infection in 2004-2014 / 中华围产医学杂志

Objective To investigate the clinical features of neonatal invasive fungal infection(IFI) so as to guide diagnosis,prevention and treatment of IFI.Methods Seventy-six neonates with IFI admitted to the Neonatal Intensive Care Unit (NICU) at Children's Hospital of Fudan University from 2004 to 2014 were included in the study.Pathogens,clinical manifestation,risk factor exposure,laboratory findings,complications,and clinical outcome of neonatal IFI were analyzed.Results Seventy-six cases were diagnosed as IFI between 2004 and 2014,with an yearly increasing trend.Sixty-eight patients were premature infants (89.5％).Of the 76 cases,except one with unknown birth weight,11(14.7％),34(45.3％),20(26.7％)and 10 (13.3％) cases had birth weight ＜ 1 000 g,(≥ 1 000-＜1 500) g,(≥ 1 500-＜2 500) g and ≥ 2 500 g,respectively.The pathogens were mainly Candida (74/76,97.4％),including 26 cases of Candida albicans (34.2％).However,the incidence of non-Candida albicans infection was increasing.Candida guilliermondii was the most common in nonCandida albicans,accounting for 29.2％ (14/48).All Candida albicans were sensitive to fluconazole.One strain of Candida glabrata was resistant to fluconazole.The most common risk factors included use of broad-spectrum antibiotics(93.3％,56/60),parenteral nutrition(70.0％,42/60),central vein catheterization(53.3％,32/60),invasive ventilation(40.0％,24/60) and history of abdominal surgery(21.7％,13/60).Clinical manifestations of IFI included temperature instability,frequent apnea,increased requirement of respiratory support and feeding intolerance.Among all cases,six were diagnosed as central nervous system infection.Of the patients who received cranial MRI,46.8％(22/47) showed multiple abnormal signals in cerebral parenchyma.Fiftytwo patients were cured and seven patients died before discharge,including one death due to fungal infection.Conclusions There is an increasing trend of IFI cases in NICU,especially in premature infants.Non-Candida albicans has become the main pathogenic fungus.There are no specific clinical manifestations in neonatal IFI.Use of broad-spectrum antibiotics,parenteral nutrition and central venous catheterization are common risk factors,and preventive measures should be taken in high-risk infants.In addition,IFI in neonates may affect important organs such as central nervous system,thus early treatment is necessary in suspected patients.

Candidíase invasiva e alterações bucais em recém-nascidos prematuros / Invasive candidiasis and oral manifestations in premature newborns

OBJETIVO: Investigar a prevalência de candidíase invasiva em Unidade de Terapia Intensiva Neonatal e avaliar alterações bucais e colonização bucal por Candida spp. em recém-nascidos prematuros com baixo peso. MÉTODOS: Estudo epidemiológico descritivo em duas etapas. Na primeira, analisou-se prevalência de candidíase invasiva em base de dados de 295 prematuros com tempo de internação superior a 10 dias e peso ao nascer inferior a 2.000g. Na segunda etapa, avaliaram-se alterações bucais e colonização por Candida spp. em 65 pacientes com peso inferior a 2.000g, com até 4 semanas de idade, internados há mais de 10 dias e apresentando alterações bucais compatíveis com lesões fúngicas. Coletaram-se amostras com swab bucal e identificou-se a colonização fúngica. RESULTADOS: Na análise da base de dados, constatou-se que a prevalência de candidíase foi de 5,4%. Houve correlação com o tempo prolongado de internação (p<0,001), que foi, em média, de 31 dias, com risco de desenvolver infecção de 85% nos primeiros 25 dias. Houve correlação com o baixo peso ao nascer (p<0,001), com média de 1.410g. No exame dos pacientes, constatou-se que as alterações bucais mais frequentes foram placas brancas, moles, destacáveis localizadas na mucosa jugal e língua. Houve colonização bucal expressiva por Candida spp. (80%). CONCLUSÃO: A frequência de candidíase invasiva foi baixa e teve correlação com baixo peso ao nascer e tempo de internação prolongado. As alterações bucais mais frequentes foram placas brancas compatíveis com candidíase pseudomembranosa e a colonização por Candida spp. foi acima da média.

OBJECTIVE: To investigate prevalence of invasive candidiasis in a Neonatal Intensive Care Unit and to evaluate oral diseases and Candida spp. colonization in low birth weight preterm newborns. METHODS: A descriptive epidemiological study performed in two stages. First, prevalence of candidiasis was analyzed in a database of 295 preterm patients admitted to hospital for over 10 days and birth weight less than 2,000g. In the second stage, oral changes and Candida spp. colonization were assessed in 65 patients weighing less than 2,000g, up to 4 week-old, hospitalized for over 10 days and presenting oral abnormalities compatible with fungal lesions. Swab samples were collected in the mouth to identify fungi. RESULTS: Prevalence of candidiasis was 5.4% in the database analyzed. It correlated with prolonged hospital length of stay (p<0.001), in average, 31 days, and 85% risk of developing infection in the first 25 days. It correlated with low birth weight (p<0.001), with mean of 1,140g. The most frequent alterations were white soft plaques, detachable, in oral mucosa and tongue. Intense oral colonization by Candida spp was observed (80%). CONCLUSIONS: The frequency of invasive candidiasis was low and correlated with low birth weight and prolonged hospital stay. The most common oral changes were white plaques compatible with pseudomembranous candidiasis and colonization by Candida spp. was above average.