[Clinical and cost characterization of hospitalization associated with varicella in children from the Metropolitan Region and Valparaíso, Chile]. / Caracterización clínica y de costos de la hospitalización asociada a varicela en niños de la Región Metropolitana y de Valparaíso, Chile.

BACKGROUND: Varicella is a relevant infection in Chile and may cause serious complications and death, which could be associated with significant health care resource utilization and associated costs. In Chile, sentinel surveillance is carried out only on an outpatient basis, without knowing the impact of varicella in serious cases who need to be hospitalized. AIM: To describe the clinical characteristics and the costs associated with hospitalized children with diagnosis of varicella prior to the vaccine introduction in the National Immunization Program in Chile. PATIENTS AND METHODS: A multicenter, observational, and retrospective study in hospitalized children (0-15 years) with a diagnosis of varicella, were conducted in five hospitals in Chile between January 2011 and December 2015. A review of the clinical records was performed to evaluate the clinical characteristics of the disease and costs associated with hospitalization episodes for varicella. RESULTS: A total of 685 hospitalized children for varicella were included in this study. The median age was 3 years (IQR: 1-5), most children were between 1 and 4 years of age (52% of total cases). 56% were male, and only 7 patients (1%) had a history of previous varicella vaccination. The median lenght of days of hospitalization was 3 days (IQR: 2-5). 13% of the cases required hospitalization in a more complex care unit, 6% in the intermediate unit and 7% in the pediatric intensive treatment unit, both with a median stay of 3 days. The main complications were: skin and soft tissue infections (42%), neurologic (8%) and septic or toxic shock (4%). There were 3 cases of death (0.4%). The direct cost of a varicella case was US $ 417, the indirect cost was US $ 224 and the proportional cost of a case of death was US $ 3,575. It is estimated that the total cost of a hospitalized varicella case in Chile was US $ 4,216. CONCLUSIONS: Varicella is associated with a significant burden of disease in Chile. The median hospital stay was three days with 13% of cases requiring medical care in a complex unit, with high associated costs which could be significantly reduced with the recently incorporation of the varicella vaccine into the National Immunization Program.

[Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation]. / Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos.

BACKGROUND: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. AIM: To determine clinical outcome of RVI, compared to BI in children with HSCT. METHODS: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. RESULTS: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). CONCLUSION: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

[Clinical characteristics and microbiological profile of viridans group streptococci bacteremia in children with cancer and high-risk febrile neutropenia]. / Caracterización clínica y microbiológica de episodios de bacteriemia por Streptococcus grupo viridans en niños con cáncer y neutropenia febril de alto riesgo.

BACKGROUND: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity. AIM: To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile. METHOD: Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains. RESULTS: 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to ß lactams. As expected, there were not non-susceptible strains to vancomycin. DISCUSSION: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to ß lactams is an issue that requires strict epidemiological surveillance in this population.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Caracterización clínica y de costos de la hospitalización asociada a varicela en niños de la Región Metropolitana y de Valparaíso, Chile / Clinical and cost characterization of hospitalization associated with varicella in children from the Metropolitan Region and Valparaíso, Chile

INTRODUCCIÓN: La varicela es una infección relevante en la salud pública de Chile, pudiendo causar en algunas ocasiones complicaciones graves e incluso la muerte, lo que se asocia a un significativo gasto en salud. En Chile sólo se realiza vigilancia centinela a nivel ambulatorio, sin conocerse el impacto de la varicela en casos más graves que determinan hospitalización. OBJETIVOS: Realizar una descripción clínica y de los costos asociados a la atención de niños hospitalizados con diagnóstico de varicela, en años previos a la introducción de la vacuna en el Programa Nacional de Inmunización en Chile. MATERIALES Y MÉTODOS: Estudio multicéntrico, observacional y retrospectivo, en todos los casos de niños hospitalizados (0-15 años) con diagnóstico de varicela, entre enero de 2011 y diciembre de 2015 en cinco hospitales de Chile. Se realizó revisión de fichas para evaluar características clínicas de la enfermedad y los costos asociados a la hospitalización por varicela. RESULTADOS: Un total de 685 hospitalizaciones por varicela fueron incluidas en el estudio. La mediana de edad fue de 3 años (RIC:1-5), siendo la mayoría de los niños con edades comprendidas entre los 1 y 4 años (52% del total de casos). El 56% fueron hombres y sólo 7 niño s (1%) tuvieron antecedente de vacuna varicela. La mediana de días de hospitalización fue de 3 días en cada episodio (RIC: 2-5). El 13% de los casos requirió hospitalización en unidades de mayor complejidad, 7% de los niños ingresó a Unidad de Tratamiento Intensivo y 6% ingresó a Intermedio, ambos con una mediana de 3 días de hospitalización. Las principales complicaciones fueron: infección de piel y tejidos blandos (42%), alteraciones neurológicas (8%) y shock séptico/tóxico (4%). La letalidad fue de 0,4%. El costo de un caso de varicela considerando los costos directos fue de US$417, el costo indirecto fue de US$224 y los costos proporcionales de una muerte de US$3.575. Se estima que el costo total de un caso de varicela hospitalizado en Chile, considerando todos los factores anteriores, fue de US$4.216. CONCLUSIONES: La varicela es una enfermedad inmunoprevenible frecuente. Se observaron casos con una mediana de 3 días de hospitalización por complicaciones, con 13% de los casos requiriendo hospitalización en unidades de mayor complejidad, con un alto costo asociado, que se estima podría disminuir significativamente con la reciente incorporación de la vacuna al Programa Nacional de Inmunizaciones.

BACKGROUND: Varicella is a relevant infection in Chile and may cause serious complications and death, which could be associated with significant health care resource utilization and associated costs. In Chile, sentinel surveillance is carried out only on an outpatient basis, without knowing the impact of varicella in serious cases who need to be hospitalized. AIM: To describe the clinical characteristics and the costs associated with hospitalized children with diagnosis of varicella prior to the vaccine introduction in the National Immunization Program in Chile. PATIENTS AND METHODS: A multicenter, observational, and retrospective study in hospitalized children (0-15 years) with a diagnosis of varicella, were conducted in five hospitals in Chile between January 2011 and December 2015. A review of the clinical records was performed to evaluate the clinical characteristics of the disease and costs associated with hospitalization episodes for varicella. RESULTS: A total of 685 hospitalized children for varicella were included in this study. The median age was 3 years (IQR: 1-5), most children were between 1 and 4 years of age (52% of total cases). 56% were male, and only 7 patients (1%) had a history of previous varicella vaccination. The median lenght of days of hospitalization was 3 days (IQR: 2-5). 13% of the cases required hospitalization in a more complex care unit, 6% in the intermediate unit and 7% in the pediatric intensive treatment unit, both with a median stay of 3 days. The main complications were: skin and soft tissue infections (42%), neurologic (8%) and septic or toxic shock (4%). There were 3 cases of death (0.4%). The direct cost of a varicella case was US $ 417, the indirect cost was US $ 224 and the proportional cost of a case of death was US $ 3,575. It is estimated that the total cost of a hospitalized varicella case in Chile was US $ 4,216. CONCLUSIONS: Varicella is associated with a significant burden of disease in Chile. The median hospital stay was three days with 13% of cases requiring medical care in a complex unit, with high associated costs which could be significantly reduced with the recently incorporation of the varicella vaccine into the National Immunization Program.

Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos / Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation

Resumen Introducción: Los niños que reciben trasplante de precursores hematopoyéticos (TPH) pueden presentar infecciones respiratorias virales (IRV) durante episodios febriles. Los datos sobre su evolución clínica son escasos, así como la comparación de ellos con infecciones bacterianas (IB). Objetivo: Caracterizar la evolución clínica de pacientes con IRV, en comparación con IB en niños con TPH, cursando un episodio febril. Método: Estudio prospectivo en pacientes ≤ 18 años con cáncer y TPH ingresados por fiebre en el Hospital Luis Calvo Mackenna (2016-2019). Se realizó evaluación clínica y de laboratorio: hemocultivos, RPC para patógenos respiratorios (Filmarray®), cuantificación viral y medición de citoquinas en muestra nasal (Luminex®, 38 citoquinas). Se compararon los grupos IRV, IB y los de etiología no precisada (ENP) en relación con: infección respiratoria aguda (IRA), citoquinas nasales, ingreso a UCI, necesidad de ventilación mecánica, mortalidad y suspensión de antimicrobianos. Resultados: De 56 episodios febriles, 35 fueron IRV, 12 IB y 9 de ENP. Mediana de edad fue 8,5 años, 62% masculino. Un 94% de los casos IRV presentó IRA sintomática, versus 33% en los grupos IB y ENP (p < 0,001), con IRA baja en 69% de las IRV (p < 0,001). Rinovirus (54%) y coronavirus (15%) fueron las etiologías más frecuentemente detectadas. No hubo diferencias en citoquinas nasales entre los grupos IRV e IB. Ingreso a UCI: 11% del grupo IRV, 17% de IB y 11% de ENP (p = 0,88). Requirieron ventilación mecánica sólo 2 pacientes (p = 0,37) sin fallecimiento. Tras la detección viral respiratoria por RPC, se suspendió antimicrobianos en 26% de los casos con IRV (p = 0,04). Conclusión: Las IRV son frecuentes en niños con TPH y episodios febriles. La detección viral podría optimizar y racionalizar el uso de antimicrobianos en esta población.

Abstract Background: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. Aim: To determine clinical outcome of RVI, compared to BI in children with HSCT. Methods: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. Results: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). Conclusion: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

Caracterización clínica y microbiológica de episodios de bacteriemia por Streptococcus grupo viridans en niños con cáncer y neutropenia febril de alto riesgo / Clinical characteristics and microbiological profile of viridans group streptococci bacteremia in children with cancer and high-risk febrile neutropenia

Resumen Introducción: Streptococcus grupo viridans (SGV) ha adquirido relevancia como microorganismo causante de neutropenia febril, asociándose a morbilidad significativa. Objetivo: Caracterizar episodios de bacteriemia causados por SGV en niños con cáncer que desarrollaron neutropenia febril de alto riesgo (NFAR) desde abril de 2004 a junio de 2018 en seis hospitales pediátricos de Santiago, Chile. Pacientes y Métodos: Análisis retrospectivo de bases de datos de cuatro proyectos FONDECYT sucesivos, prospectivos y multicéntricos, registrando características clínicas y de laboratorio de los pacientes, además de patrón de resistencia antimicrobiana de las cepas aisladas. Resultados: Se registraron 95 episodios de bacteriemia asociada a SGV en 91 niños con NFAR. Destacan: leucemia mieloide aguda como enfermedad de base, neutropenia profunda, hospitalización prolongada (15 días), uso extendido de antimicrobianos (14 días), uso de citarabina en esquemas de quimioterapia (86% episodios). Las manifestaciones clínicas más frecuentes fueron respiratoria y gastrointestinal, asociándose en 26% a síndrome de shock por Streptococcus grupo viridans. Hubo elevada resistencia a β lactámicos, sin cepas no susceptibles a vancomicina. Discusión: SGV es un patógeno relevante en niños con cáncer, fiebre y neutropenia en nuestro medio, asociado a casos de sepsis. La resistencia a β lactámicos es un aspecto que requiere vigilancia epidemiológica estricta en esta población.

Abstract Background: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity. Aim: To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile. Method: Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains. Results: 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to β lactams. As expected, there were not non-susceptible strains to vancomycin. Discussion: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to β lactams is an issue that requires strict epidemiological surveillance in this population.

Microorganismos aislados de hemocultivos en niños con cáncer y neutropenia febril de alto riesgo en cinco hospitales de Santiago, Chile, período 2012-2015 / Microorganisms isolated from blood cultures in children with cancer and high-risk febrile neutropenia from five hospitals in Santiago, Chile, 2012-2015

Resumen Antecedentes: Los microorganismos aislados de hemocultivos (HC) en pacientes con neutropenia febril (NF) varían en el tiempo, siendo necesaria su vigilancia para orientar una terapia empírica adecuada. Objetivo: Identificar microorganismos aislados de HC y su perfil de resistencia (R) a antimicrobianos en niños con cáncer y NF de alto riesgo. Método: Estudio prospectivo, multicéntrico de episodios de NF de alto riesgo en pacientes bajo 18 años de edad, de cinco hospitales en Santiago de Chile, 2012-2015. Análisis de HC positivos. Resultados: Se analizaron 206 microorganismos en 185 episodios de NF de alto riesgo con HC positivos. Los aislados principales fueron bacilos gramnegativos (BGN) (46,6%) y cocáceas grampositivas (CGP) (45,1%) y los microorganismos más frecuentes Escherichia coli (22,8%), Staphylococcus coagulasa negativa (18,0%) y Klebsiella spp (16,5%). En resistencia (R) a antimicrobianos destaca: E. coli y Klebsiella spp 4,2 y 67,6% R a cefalosporinas de tercera generación (cefotaxima/ceftriaxona) respectivamente, 10,6 y 40,6% R a ciprofloxacina y 2,1 y 26,5% a amikacina, respectivamente. S. coagulasa negativa y S. aureus 86,4% y 22,2% R a oxacilina, Streptococcus grupo viridans 71% R a penicilina. Discusión: Este estudio actualiza la etiología y el perfil de R de microorganismos aislados en HC de niños con cáncer y NF de alto riesgo, herramienta esencial para el adecuado manejo de estos pacientes.

Background: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy. Aim: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF. Method: Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015. Results: A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin. Discussion: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.