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.

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.

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.

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.

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.

Ten-year review of invasive Candida infections in a tertiary care center in Saudi Arabia

To review the epidemiology of invasive Candida infections in a single center in Saudi Arabia over a subsequent 10-year period. This retrospective study was carried out in a single center in Saudi Arabia over a 10-year period. Records of all patients with invasive Candida infections [ICI] over the period from January 2003 to December 2012 were reviewed. Mann-Whitney U test was used for comparison of Candida albicans [C. albicans] versus non-albicans Candida species, and fluconazole resistance versus fluconazole susceptible in relation to crude mortality at 30 days and 90 days. Eight hundred positive sterile site cultures, associated with 652 ICI were identified. Median age was 52 years and 53% of patients were males. Candida albicans were the most common species [38.7%], followed by Candida tropicalis [18.9%], and Candida glabrata [C. glabrata] [16.3%]. The proportion of ICI caused by C. albicans remained stable over time [p=0.07], but C. glabrata increased significantly [p<0.001]. The median rate of ICI per 1,000 hospital discharges per year was 1.65, with a significant trend towards higher rates over time [p=0.01]. Most isolates were susceptible to fluconazole, voriconazole, and amphotericin B. Only 66.7% of Candida krusei were susceptible to caspofungin. Overall 30-day crude mortality was 40.6%. There was no significant difference in crude mortality in association with C. albicans compared with non-albicans species, nor in association with fluconazole resistance. The rate of ICI increased significantly in the proportion of ICI caused by C. glabrata. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. The crude mortality remains high

Invasive candidosis: contrasting the perceptions of infectious disease physicians and intensive care physicians

Introduction We analyze how infectious disease physicians perceive and manage invasive candidosis in Brazil, in comparison to intensive care unit specialists. Methods A 38-question survey was administered to 56 participants. Questions involved clinicians' perceptions of the epidemiology, diagnosis, treatment and prophylaxis of invasive candidosis. P < 0.05 was considered statistically significant. Results The perception that candidemia not caused by Candida albicans occurs in less than 10% of patients is more commonly held by intensive care unit specialists (p=0.018). Infectious disease physicians almost always use antifungal drugs in the treatment of patients with candidemia, and antifungal drugs are not as frequently prescribed by intensive care unit specialists (p=0.006). Infectious disease physicians often do not use voriconazole when a patient's antifungal treatment has failed with fluconazole, which also differs from the behavior of intensive care unit specialists (p=0.019). Many intensive care unit specialists use fluconazole to treat candidemia in neutropenic patients previously exposed to fluconazole, in contrast to infectious disease physicians (p=0.024). Infectious disease physicians prefer echinocandins as a first choice in the treatment of unstable neutropenic patients more frequently than intensive care unit specialists (p=0.013). When candidemia is diagnosed, most infectious disease physicians perform fundoscopy (p=0.015), whereas intensive care unit specialists usually perform echocardiograms on all patients (p=0.054). Conclusions This study reveals a need to better educate physicians in Brazil regarding invasive candidosis. The appropriate management of this disease depends on more drug options being available in our country in addition to global coverage in private and public hospitals, thereby improving health care. .

Invasive candidiasis: A review of nonculture-based laboratory diagnostic methods.

Invasive candidiasis is a life-threatening complication of critically ill immunocompromised patients with high attributable mortality. Due to non-specific clinical presentation, early detection of candidemia and accurate identification of Candida species are essential pre-requisites for improved therapeutic outcome. Since blood culture-based methods lack sensitivity and species-specific identification by conventional methods is time-consuming, detection of immunological and molecular markers has provided an alternative for early diagnosis of invasive candidiasis. Additionally, serial estimations of these biomarkers have provided opportunities to monitor response to therapy and initiate pre-emptive therapy in suspected patients before clinical signs appear. Antigen-based methods include detection of β-D-glucan, a panfungal marker, and Candida mannan, a genus-specific marker. Although both these markers have moderate sensitivity, they provide a useful adjunct to the diagnosis if performed in select patient population in parallel for exclusion of false positive/negative results. A negative β-D-glucan test on at least two occasions has a high negative predictive value. Concomitant detection of Candida mannan and anti-mannan antibodies has sensitivity of ~70% before blood cultures become positive. Significant advances have also been made in nucleic acid-based detection methods, including a commercial real-time PCR assay (SeptiFast) for detection of five major clinically important Candida spp. in blood specimens within 6 h. Furthermore, matrix-assisted laser desorption ionization time-of-flight mass spectrometry enables species-specific identification of yeast isolates within an hour. While these immunological and molecular tools mark a significant advance towards early and specific diagnosis of candidemia and invasive candidiasis, further evaluation of these approaches in different clinical settings is warranted.

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.