Infecciones fúngicas invasivas en niños hospitalizados en un centro de referencia de Uruguay / Invasive fungal infections in children hospitalized at a pediatric reference hospital in Uruguay / Infecções fúngicas invasivas em crianças internadas em um centro hospitalar de referência no Uruguai

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.

Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.

Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.

Candidiasis invasora: un enfoque a la infección en el sistema nervioso central

Resumen La candidemia es la micosis invasora más frecuente en los pacientes internados en hospitales de alta complejidad en el mundo. La infección fúngica en el sistema nervioso central constituye una complicación potencialmente mortal que agrava el pronóstico de los pacientes. El presente artículo aborda aspectos relevantes sobre las características clínicas de esta enfermedad, los mecanismos de invasión del hongo, la respuesta inmunitaria local frente a Candida albicans y el impacto de los defectos genéticos en receptores de la inmunidad innata, que aumentan la susceptibilidad a la neurocandidiasis.

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.

A Ten-year Retrospective Study of Invasive Candidiasis in a Tertiary Hospital in Beijing / 生物医学与环境科学（英文）

Objective@#This study aimed to evaluate the epidemiological, clinical and mycological characteristics of invasive candidiasis (IC) in China.@*Methods@#A ten-year retrospective study including 183 IC episodes was conducted in a tertiary hospital in Beijing, China.@*Results@#The overall incidence of IC from 2010-2019 was 0.261 episodes per 1,000 discharges. Candidemia (71.0%) was the major infective pattern; 70.3% of the patients tested positive for @*Conclusion@#The incidence of IC has declined in the recent five years.

Estudo do potencial antifúngico e do mecanismo de ação do timol contra cepas de Candida parapsilosis resistentes ao fluconazol e a anfotericina B / Study of the antifungal potential and mechanism of action of thymol against strains of Candida parapsilosis resistant to fluconazole and amphotericin B

Objetivo: investigar a suscetibilidade de cepas fúngicas de Candida parapsilosis isoladas de sangue humano frente ao timol, bem como seu mecanismo de ação. Metodologia: foram utilizadas técnicas de microdiluição em placas de 96 poços para determinar a concentração inibitória mínima (CIM) e concentração fungicida mínima (CFM). Além disso, foram realizados testes com o sorbitol e o ergosterol para investigar a ação do timol na parede e na membrana celular fúngica respectivamente. Resultados: nos testes de CIM e CFM, foi observado que as cepas de C. parapsilosis são resistentes ao fluconazol e a anfotericina B, no entanto, o timol desempenhou efeito fungicida com razão CFM/CIM entre 1 e 2. Além disso, a CIM do timol não aumentou quando o sorbitol ou o ergosterol foi adicionado no meio, sugerindo fortemente que este monoterpeno não age na parede celular fúngica ou por ligação ao ergosterol na membrana plasmática. Conclusão: portanto, esses resultados contribuem para a elucidação do mecanismo de ação do timol, sugerindo outros possíveis alvos de interação fármaco-receptor. No entanto, mais investigações de caráter enzimático e molecular em modelos in vitro são necessários para que se possa elucidar completamente o modo de ação desse promissor monoterpeno.

Objective: to investigate the susceptibility of fungal strains of Candida parapsilosis isolated from human blood against thymol, as well as its mechanism of action. Methodology: microdilution techniques were used in 96-well plates to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). In addition, tests were performed with sorbitol and ergosterol to investigate the action of thymol on the wall and on the fungal cell membrane respectively. Results: in the CIM and CFM tests, it was observed that C. parapsilosis strains are resistant to fluconazole and amphotericin B, however, thymol had a fungicidal effect with MFC/MIC ratio between 1 and 2. In addition, thymol MIC did not increase when sorbitol or ergosterol was added in the medium, strongly suggesting that this monoterpene does not act on the fungal cell wall or by binding to ergosterol on the plasma membrane. Conclusion: therefore, these results contribute to the elucidation of the mechanism of action of thymol, suggesting other possible targets of drug-receptor interaction. However, further investigations of enzymatic and molecular character in in vitro models are necessary to fully elucidate the mode of action of this promising monoterpene.

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.

Colombian consensus on the diagnosis, treatment, and prevention of Candida Spp. disease in children and adults, / Consenso Colombiano Para el Diagnóstico, Tratamiento y Prevención de la Enfermedad por Candida Spp. en Niños y Adultos

Invasive Candidiasis (IC) and candidemia (as its most frequent manifestation) have become the main cause of opportunistic mycosis at hospital settings. This study, made by members of the Colombian Association of Infectious Diseases (ACIN), was aimed at providing a set of recommendations for the management, follow-up and prevention of IC / candidemia and mucous membrane candida infection in adult, pediatric and neonatal patients in a hospital setting, including the hemato-oncological and critical care units. All the data obtained through an exhaustive search were reviewed and analyzed in a comprehensive manner by all the members of the group, and the recommendations issued are being made after a careful review of the scientific literature available and the consensus of all specialists involved; the emergence of Candida Spp. problem is highlighted and a correct orientation to health professionals regarding the management of patients with candidiasis is provided in a rational and practical way, emphasizing patient evaluation, diagnostic strategies, prophylaxis, empirical treatment, directed treatment and preventative therapy.

La Candidiasis Invasora (CI) y la candidemia, como su manifestación más frecuente, se ha convertido en la principal causa de micosis oportunista a nivel hospitalario. Este manuscrito realizado por miembros de la Asociación Colombiana de Infectología (ACIN), tuvo como objetivo proporcionar un conjunto de recomendaciones para manejo, seguimiento y prevención de la CI/candidemia y de la infección candidiásica de mucosas, en población adulta, pediátrica y neonatal, en un entorno hospitalario, incluyendo las unidades hemato-oncológicas y unidades de cuidado crítico. Todos los datos obtenidos mediante una búsqueda exhaustiva, fueron revisados y analizados de manera amplia por todos los miembros del grupo, y las recomendaciones emitidas se elaboraron luego de la evaluación de la literatura científica disponible, y el consenso de todos los especialistas involucrados, reconociendo el problema de la emergencia de las infecciones por Candida Spp. y brindando una correcta orientación a los profesionales de la salud sobre el manejo de pacientes con enfermedad candidiásica, de una forma racional y práctica, enfatizando en la evaluación del paciente, estrategias de diagnóstico, profilaxis, tratamiento empírico, tratamiento dirigido y terapia preventiva.

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.

Comparison of the identification results of Candida species obtained by BD PhoenixT and Maldi-TOF (Bruker Microflex LT Biotyper 3.1) / Comparación de los resultados de identificación de especies del género Candida obtenidos por BD PhoenixT y Maldi-TOF (Bruker Microflex LT Biotyper 3.1)

In patients with invasive fungal infections, the accurate and rapid identification of the genus Candida is of utmost importance since antimycotic sensitivity is closely related to the species. The aim of the present study was to compare the identification results of species of the genus Candida obtained by BD PhoenixT (Becton Dickinson -#91;BD-#93;) and Maldi-TOF MS (Bruker Microflex LT Biotyper 3.1). A total of 192 isolates from the strain collection belonging to the Mycology Network of the Autonomous City of Buenos Aires, Argentina, were analyzed. The observed concordance was 95%. Only 10 strains (5%) were not correctly identified by the BD PhoenixT system. The average identification time with the Yeast ID panels was 8h 22 min. The BD PhoenixT system proved to be a simple, reliable and effective method for identifying the main species of the genus Candida.

En pacientes con infecciones fúngicas invasoras, la identificación certera y rápida de las especies del género Candida es de suma importancia, ya que la sensibilidad a los antifúngicos está íntimamente relacionada con la especie. El objetivo del presente estudio fue comparar los resultados de identificación de especies del género Candida obtenidos con el equipo comercial BD PhoenixT (Becton Dickinson -#91;BD-#93;) y con la técnica de Maldi-TOF MS (Bruker Microflex LT Biotyper 3.1.) Se analizaron 192 aislamientos provenientes del cepario perteneciente a la Red deMicología de la Ciudad Autónoma de Buenos Aires, Argentina. La concordancia observada fue del 95%. Solo 10 cepas (5%) no fueron identificadas correctamente por el sistema BD PhoenixT. El tiempo promedio de identificación con los paneles Yeast ID fue de 8 h 22 min. El sistema BD PhoenixT demostró ser un método simple, confiable y efectivo para la identificación de las principales especies del género Candida.

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins / Identificação e susceptibilidade de isolados clínicos de Candida spp. para toxinas assassinas

Abstract Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.

Resumo Embora as infecções invasivas e a mortalidade causada por espécies de Candida estejam aumentando entre pacientes comprometidos, a resistência a agentes antifúngicos comuns também é um problema crescente. Analisamos 60 leveduras isoladas de pacientes com candidíase invasiva utilizando como estratégia PCR/RFLP baseada na região espaçadora transcrita interna (ITS2) para identificar diferentes espécies patogênicas de Candida. A análise por PCR foi realizada a partir de ADN genómico com um par de iniciadores da região ITS2-5.8S rDNA. As amostras PCR-positivas foram caracterizadas por RFLP. A restrição resultou em 23 isolados identificados como C. albicans usando AlwI, 24 isolados como C. parapsilosis usando RsaI e 13 como C. tropicalis usando XmaI. Em seguida, avaliou-se o grupo de todos os isolados quanto à sua susceptibilidade a um painel de leveduras killer previamente descritas, resultando em 75% sendo suscetíveis a pelo menos uma levedura killer, enquanto que as restantes não foram inibidas por qualquer cepa. C. albicans foi o grupo mais suscetível enquanto C. tropicalis teve o menor número de inibições. Não se obteve um padrão de inibição específico da espécie com este painel de leveduras killer. Metschnikowia pulcherrima, Pichia kluyveri e Wickerhamomyces anomalus foram as cepas que inibiram a maioria dos isolados de Candida spp.

Evaluación del rendimiento de 1, 3-β -d-glucano como apoyo diagnóstico de infecciones invasoras por Candida spp. en pacientes críticos adultos / The 1,3-β -d-glucan in critical adult patients as diagnostic tool for invasive Candida spp. infection, performance evaluation

Resumen Introducción: La enfermedad fúngica invasora (EFI) se reconoce como causa importante de morbi-mortalidad en pacientes críticos. La mayoría de estas infecciones son provocadas por Candida spp. para cuyo diagnóstico existen importantes limitaciones. Objetivo: Realizar una evaluación inicial de la utilidad de la medición del 1,3-β-D- glucano (BDG) como herramienta diagnóstica de apoyo de las infecciones invasoras por Candida spp. en pacientes críticos. Pacientes y Método: Estudio prospectivo de pacientes mayores de 18 años hospitalizados en unidades de pacientes críticos por más de cinco días, con fiebre sin foco claro y dos o más factores de riesgo para EFI por Candida spp. Se obtuvieron muestras para BDG en dos días consecutivos. Los resultados se confrontaron con el diagnóstico definitivo de candidemia/candidiasis invasora (C/CI) demostrado según cultivos. Resultados: El valor promedio de BDG en los pacientes con diagnóstico de C/CI fue 224,3 ± 213,7 pg/ml y en aquellos sin C/CI 63,8 ± 76,7 pg/ml (p: 0,02). La sensibilidad y especificidad de BDG para diagnóstico de C/CI fue 60 y 92%, respectivamente. El valor predictor positivo fue 60% y el valor predictor negativo de 92%. Conclusión: BDG puede considerarse como un examen de apoyo en el diagnóstico de C/CI en pacientes críticos con factores de riesgo.

Background: Invasive fungal infections are important causes of morbimortality in critical patients. Most of these infections are caused by Candida spp. which diagnosis has important limitations. Aim: Initial evaluation of the utility of 1,3-β-D-glucan (BDG) as a diagnostic tool for invasive candida infections in critical patients. Patients and Methods: Adult patients over 18 years old, hospitalized in intensive care units for more than five days, with fever > 38 °C of unclear origin and two or more risk factors for invasive Candida spp. infection were included. Samples for BDG were obtained on two consecutive days. The results were compared with definitive diagnosis of candidemia/invasive candidiasis (C/IC) confirmed by cultures. Results: Median value of BDG in patients with C/IC was 224.3 ± 213.7 pg/ml and in patients without C/IC was 63.8 ± 76.7 pg/ml (p: 0.02). Sensitivity and specificity for the diagnosis of C/IC were 60 and 92%, respectively. Positive predictive value was 60% and negative predictive value was 92%. Conclusion: BDG could be considered as a complementary diagnostic tool for the diagnosis of C/IC in critical patients with risk factors.

Fluconazole prophylaxis in preterm infants: a systematic review

ABSTRACT Objective: This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. Methods: This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Results: Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Conclusion: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.

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.

Candidiasis intraabdominal masiva secundaria a cirugías digestivas en pacientes inmunocompetentes. A propósito de 2 casos / Massive intra-abdominal candida infection secondary to digestive surgery in inmunocompetent patients: A report on 2 cases

La perforación asociada a infección intraabdominal difusa por Candida spp. es excepcional. Suele asociarse a pacientes inmunodeprimidos o con enfermedad tumoral avanzada. Presentamos 2 casos de perforación digestiva secundaria a candidiasis invasiva. En el primer caso, una mujer de 68 años con una perforación duodenal secundaria a Candida spp., se realiza laparotomía exploradora y reparación de la perforación duodenal. Sin embargo, la paciente requiere más de 2 intervenciones, observándose Candida spp. macroscópica diseminada por toda la cavidad abdominal. El segundo caso es el de un varón de 60 años que presenta un postoperatorio complicado de una hemicolectomía derecha, que se asocia con pancretitis, y con posterior diseminación fúngica abdominal secundaria a Candida parapsilopsis, con múltiples complicaciones infecciosas. En ambos casos se intentó un tratamiento basado en resección quirúrgica y cambio de anti-fúngicos, sin éxito. El tratamiento antifúngico precoz evita la diseminación hematógena y el shock séptico, disminuyendo la morbimortalidad de estos pacientes.

Candida spp. as cause of diffuse intraabdominal infection is very rare. Often associated with immunocompromised or patients with advanced tumor disease. We are reporting 2 cases of gastrointestinal perforation secondary to invasive candidiasis. The first case, a 68 years old female with a Candida spp. duodenal perforation. An emergency exploratory laparotomy was performed and a duodenal perforation repair was done. However, the patient required 2 more reoperation due to Candida spp. macroscopic intra-abdominal disemination. The second case, is presented in the context of a postoperative period of a right hemicolectomy, pancreatitis associating abdominal spread and subsequent secondary fungal Candida parapsilopsis with multiple infectious complications. In both cases there were unsuccessful surgical resection and antifungal change. The early antifungal treatment prevents hematogenous dissemination and septic shock, reducing the morbidity and mortality of these patients.

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.

Tuberculosis ineection might increase the risk f invasive candidiasis in an immmunocompetent patient / Tuberculose pode aumentar o risco de candidíase invasiva em paciente imunocompetente

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicans and spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient.

As infecções profundas por Candida ocorrem geralmente em pacientes imunossuprimidos. Relatamos caso raro de infecções profundas em múltiplos órgãos por Candida albicans e neuro tuberculose em homem jovem saudável. Um jovem de 19 anos de idade queixou-se de febre e lombalgia há um mês. Relatava ainda histórico de síndrome da boca escaldada. Foi diagnosticada co-infecção por Mycobacterium tuberculosis e Candida albicans em cultura do aspirado de diferentes regiões do organismo. Os sintomas melhoraram significativamente após a terapia antifúngica e antituberculosa. Este caso é apresentado para mostrar que a tuberculose pode prejudicar o sistema imune do hospedeiro e aumentar o risco de candidíase invasiva em paciente imunocompetente.

Infecciones fúngicas en un Servicio de Terapia Intensiva de Adultos de un hospital especializado / Fungal infections in Intensive Care Service of a specialized hospital Adults

RESUMEN Introducción: las infecciones fúngicas son frecuentes en las Unidades de Terapia Intensiva, debida a múltiples factores predisponentes. Objetivos: determinar la prevalencia de infecciones fúngicas y las características clínicas de los pacientes afectados. Metodología: estudio observacional, descriptivo, retrospectivo, realizado en pacientes adultos internados en el Servicio de Terapia Intensiva del Hospital Nacional (Itauguá, Paraguay) en el año 2013. Resultados: fueron incluidos 1034 pacientes, encontrándose 85 con infección por hongos (prevalencia 8,22%). Las especies más frecuentemente aisladas fueron: Cándida spp. (51,76%), C. tropicalis (27,06%) y C. albicans (14,12%). Las comorbilidades más frecuentes fueron hipertensión arterial (91,76%), diabetes mellitus (44,71%) y obesidad (28,24%). Los sitios de aislamientos predominantes fueron el urocultivo (51,76%), hemocultivo (22,35%) y secreción traqueal (21,18%). Hubo 26 óbitos (30,59%). Los factores asociados al óbito fueron los score APACHE y SOFA elevados. Conclusiones: la prevalencia de infecciones fúngicas fue 8,22%, con predominio de Cándida spp. La mortalidad fue 30,59%.

ABSTRACT Introduction: fungal infections are common in intensive care units due to multiple risk factors. Objectives: To determine the prevalence of fungal infections and clinical characteristics of affected patients. Methodology: observational, descriptive and retrospective study, conducted in adult patients admitted to the Intensive Care Service of the National Hospital (Itauguá, Paraguay) in 2013. Results: 1034 patients were included, been 85 with patients affected fungal infection (prevalence 8, 22%). The most frequently isolated species were: Candida spp. (51.76%), C. tropicalis (27.06%) and C. albicans (14.12%). The most common comorbidities were hypertension (91.76%), diabetes mellitus (44.71%) and obesity (28.24%). Predominant sites of isolation were urine culture (51.76%), blood culture (22.35%) and tracheal secretion (21.18%). There were 26 deaths (30.59%). Factors associated with death were the high APACHE score and SOFA. Conclusions: The prevalence of fungal infections were 8.22%, with a predominance of Candida spp. Mortality was 30.59%.

Identificación molecular de Candida lusitaniae en infección de tracto respiratorio inferior / Molecular identification of Candida lusitaniae in lower respiratory tract infection

Candida lusitaniae es una levadura que ha sido descrita como un patógeno nosocomial emergente de baja frecuencia en infecciones profundas. La identificación oportuna de C. lusitaniae es importante porque puede desarrollar resistencia in vivo a la amfotericina B durante la terapia. Reportamos el aislamiento de C. lusitaniae como agente etiológico de infección de tracto respiratorio inferior en un paciente masculino. Los cultivos de orina y esputo fueron negativos para bacterias y positivos para esta levadura. Los aislamientos fueron identificados por métodos fenotípicos de rutina y confirmados por secuenciación y polimorfismos de longitud de fragmentos de restricción y PCR de la región espaciadora interna del DNA ribosómico.

The yeast Candida lusitaniae has been described as an emerging low frequency nosocomial pathogen in deep infections. Early identification of C. lusitaniae is important because it can readily develop in vivo resistance to amphotericin B during treatment. We report the isolation of C. lusitaniae as etiologic agent of a lower respiratory tract infection in a male patient. Urine and sputum cultures were negative for bacteria and positive for yeast. Isolates were identified by routine phenotypic methods and confirmed by ribosomal DNA internal spacer region restriction fragment length polymorphism PCR and sequencing.