Epidemiological changes of invasive fungal disease in children with cancer: Prospective study of the National Child Program of Antineoplastic Drugs network, Chile.

BACKGROUND: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high-risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016-2020 compared to 2004-2006 in six hospitals in Chile. METHODS: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004-2006. The incidence rate was estimated. RESULTS: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent-HRFN occurring in 174 patients. The median age was 7 years (IQR: 3-12 years) and 52.3% (N = 91) were male. Fifty-three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent-HRFN with an IFD incidence of 14.6% (95% CI 10.5-19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5-20.0). Compared to 2004-2006 cohort (incidence: 8.5% (95% CI 5.2-13.5)), a significant increase in incidence of 6.1% (95% CI 0.2-12.1, p = .047) was detected in cohorts between 2016 and 2020. CONCLUSION: We observed a significant increase in IFD in 2016-2020, compared to 2004-2006 period.

[Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021]. / Microorganismos aislados de hemocultivos y su perfil de resistencia en niños con cáncer y neutropenia febril de alto riesgo. Red PINDA, Chile, 2016-2021.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

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.

Consenso de la Sociedad Chilena de Infectología para el manejo de episodios de neutropenia febril en adultos y niños con cáncer / Consensus of the Chilean Society of Infectious Diseases for the management of episodes of febrile neutropenia in adults and children with cancer

El Comité de Infecciones en Inmunocomprometidos de la Sociedad Chilena de Infectología presenta aquí una actualización en el Manejo de episodios de neutropenia febril en adultos y niños con cáncer, derivado de los grandes cambios ocurridos en los últimos años en el enfrentamiento de estos pacientes. Para estos efectos, un grupo multidisciplinario desarrolló recomendaciones en relación a: su enfrentamiento inicial, exámenes de laboratorio requeridos, el tratamiento antimicrobiano inicial empírico y frente a focos infecciosos conocidos, las infecciones fúngicas invasoras y profilaxis antimicrobiana.

The Committee of Infections in Immunocompromised Patients of the Chilean Society of Infectious Diseases presents an update in the Management of febrile neutropenia in adults and children with cancer. It comes from the significant changes that occurred in recent years in the confrontation of these patients. For which a multidisciplinary task force group developed recommendations in relation to their initial handling, laboratory exams required, the initial empirical antimicrobial treatment and in front of known infectious focus, invasive fungal infections and antimicrobial prophylaxis.

Clinical Outcome in Children With Cancer With Two or More Microorganisms Isolated From Blood Cultures During Episodes of Fever and Neutropenia.

BACKGROUND: Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN. METHODS: Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation. RESULTS: A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003). CONCLUSIONS: Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation.

Manejo de los episodios de neutropenia febril en niños con cáncer: consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021 / Management of episodes of febrile neutropenia in children with cancer: consensus of the Latin American Society of Pediatric Infectious Diseases 2021

Resumen El Comité de Infecciones en el Niño Inmunocomprometido de la Sociedad Latinoamericana de Infectología Pediátrica, entrega este documento de Consenso, llamado "Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021". El documento contiene recomendaciones sobre aspectos de prevención, predicción, diagnóstico, tratamiento y pronóstico de los episodios de fiebre y neutropenia, incluyendo recomendaciones específicas sobre: Análisis de ingreso; evaluación, ajustes y duración de terapias antimicrobianas; diagnóstico y manejo de infección fúngica invasora; análisis de los principales focos clínicos de infección; condiciones ambientales necesarias para hospitales que atienden niños con cáncer y quimioprofilaxis. Se ha puesto especial énfasis en entregar las mejores recomendaciones para optimizar el manejo de los episodios de fiebre y neutropenia en niños con cáncer, buscando la equidad y la excelencia a través de todos los centros que atienden estos pacientes en América Latina.

Abstract The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

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.

Cytokine and chemokine profiles in episodes of persistent high-risk febrile neutropenia in children with cancer.

BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.

[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.

[Management of episodes of febrile neutropenia in children with cancer. Consensus of the Latin American Society of Pediatric Infectious Diseases 2021]. / Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021.

The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

Multisystem inflammatory syndrome in children (MIS-C): Report of the clinical and epidemiological characteristics of cases in Santiago de Chile during the SARS-CoV-2 pandemic.

OBJECTIVE: To describe the clinical and epidemiological characteristics of hospitalized children with multisystem inflammatory syndrome in children (MIS-C) in Santiago, Chile. METHODS: This was an observational study of children with MIS-C (May 1 to June 24, 2020), in three pediatric hospitals in Santiago. Demographic characteristics and epidemiological data, medical history, laboratory tests, cardiology evaluations, treatment, and clinical outcomes were analyzed. RESULTS: Twenty-seven patients were admitted (median age 6, range 0-14 years). Sixteen of the 27 (59%) required intensive care unit admission; there were no deaths. Seventy-four percent had no comorbidities, and the median number of days of symptoms before admission was 4 (range 2-9 days). Gastrointestinal symptoms were the most frequent, and inflammatory markers were increased at admission. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was detected in 82% of cases. The severe group showed significantly lower hemoglobin and albumin levels, decreased platelet counts, and higher d-dimer during disease evolution. Echocardiography showed abnormalities (myocardial, pericardial, or coronary) in 12 patients (46%) during their hospital stay. Anti-inflammatory treatment (immunoglobulin and/or corticosteroids) was prescribed in 24 patients. MIS-C appeared in clusters weeks after the peak of SARS-CoV-2 cases, especially in the most vulnerable areas of Santiago. CONCLUSIONS: This study describes the first series (n = 27) of children with MIS-C in a Latin American country, showing favorable clinical outcomes. Education and alerts are required for clinical teams to establish an early diagnosis and prompt treatment.

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.

Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia.

BACKGROUND: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population. OBJECTIVES: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. PATIENTS/METHODS: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds. RESULTS: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04). CONCLUSIONS: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

[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.

Mujeres jóvenes con infección por VIH adquirida por transmisión vertical: expectativas de tener hijos no infectados / Young women with HIV infection acquired by vertical transmission: expectations of having uninfected children

Introduction: Pediatric antiretroviral therapy (ART), changed the prognosis of the disease, allowing young women infected by vertical transmission (TV) to be pregnant without risk for their fetus of acquiring this infection. Aim: To describe the clinical-immune status in pregnant women that acquired HV by vertical transmission, treatments received, monitoring of pregnancy and newborn characteristics. Material and Methods: A protocol was performed, evaluating clinical and immunological parameters during pregnancy, ART used, protocol preventing vertical transmission (PPTV), and follow up of children to 18 months of age. Results: Of 358 HIV-positive patients vertically infected, five women became pregnant, between 14 and 24 years old. Pregnancies were controlled in clinical/immune-stage N2 C3. They had received two to five therapies. Full PPTV was performed in all binomials. Pre-natal undetectable viral loads ranged from 4,700 ARN copies/mL. Five living children were born by Caesarean section, four of them with 37 weeks of completed gestation and one of them with 34 weeks of gestation. All received zidovudine (AZT) for 6 weeks. CD4 at 72 hours of life ranged from 48% to 74.6%. All children were born uninfected with HIV. Only two had mild anemia. Conclusions: Expectations of HIV mothers vertically infected to have healthy children are similar to those infected by horizontal transmission, using PPTV

Introducción: La terapia anti-retroviral en pediatría (TARV), cambió el pronóstico de la enfermedad, permitiendo embarazarse a mujeres jóvenes infectadas por transmisión vertical (TV). Objetivos: Conocer las características clínico-inmunológicas de las mujeres embarazadas, tratamientos recibidos, condición al embarazo y seguimiento de sus recién nacidos. Material y Método: Se efectuó un protocolo, evaluando etapas clínico-inmunológicas en el embarazo, TARV usadas, protocolo de prevención de transmisión vertical (PPTV) y seguimiento de los niños hasta 18 meses. Resultados: De 358 pacientes con infección por VIH adquirida por TV, cinco mujeres se embarazaron, con edades entre 14 a 24 años, embarazos que fueron controlados por el equipo de salud, encontrándose en etapa clínico-inmunológica N2 a C3. Habían recibido dos a cinco esquemas de TARV. Se efectuó PPTV completo en todos los binomios. Las cargas virales previas al parto fluctuaron entre indetectable y 4.700 copias ARN/ml. Nacieron por cesárea cinco niños vivos, cuatro de término y uno con 34 semanas de gestación. Todos recibieron zidovudina (AZT) durante seis semanas. Los CD4 a las 72 h de vida fluctuaron entre 48 y 74,6%. Ninguno de los niños adquirió la infección por VIH en forma vertical. Sólo dos presentaron anemia leve. Conclusiones: Las expectativas de madres con infección por VIH de adquisición vertical de tener hijos sanos son semejantes a las infectadas por transmisión horizontal, al usar PPTV.

Respiratory Viral Infections and Coinfections in Children With Cancer, Fever and Neutropenia: Clinical Outcome of Infections Caused by Different Respiratory Viruses.

BACKGROUND: Respiratory viral infections in episodes of fever and neutropenia (FN) in children with cancer are not well characterized. We compared the clinical outcome of infections caused by different respiratory viruses (RVs) and by RV coinfection in this population. METHODS: Children with cancer and FN at 3 hospitals in Chile were prospectively evaluated by clinical examination, blood cultures and detection of 17 RVs using multiplex polymerase chain reaction (nasopharyngeal samples). Clinical characterization and outcome variables were determined and compared by the type of RV detected. RESULTS: A total of 1044 episodes of FN in 525 children were included. At least 1 RV was detected in 46%. In 350 of 1044 (34%) episodes, we detected only RVs, of which 284 (81%) were classified as a single-RV infection and 66 (19%) as a viral coinfection. Respiratory symptoms were present at admission in 65% of the episodes with any detected RV. Median age was 6 years (interquartile range, 3-10), and 51% were women. The most common RVs detected were rhinovirus, respiratory syncytial virus, parainfluenza, influenza, adenovirus and human metapneumovirus. Episodes caused by different types of RVs had no differences in the clinical outcome (days of hospitalization, days of fever, O2 requirement, admission to the intensive care unit and death) and when comparing single and viral coinfection. CONCLUSIONS: To our knowledge, this is the largest report comparing clinical outcome in FN episodes caused by different RVs in children with cancer. A positive polymerase chain reaction for RV at admission was significantly associated with the presence of respiratory symptoms. Our data showed a favorable outcome in all episodes with RV detection, including single and viral coinfections.

[Young women with HIV infection acquired by vertical transmission: Expectations of having uninfected children]. / Mujeres jóvenes con infección por VIH adquirida por transmisión vertical: Expectativas de tener hijos no infectados.

INTRODUCTION: Pediatric antiretroviral therapy (ART), changed the prognosis of the disease, allowing young women infected by vertical transmission (TV) to be pregnant without risk for their fetus of acquiring this infection. AIM: To describe the clinical-immune status in pregnant women that acquired HV by vertical transmission, treatments received, monitoring of pregnancy and newborn characteristics. MATERIAL AND METHODS: A protocol was performed, evaluating clinical and immunological parameters during pregnancy, ART used, protocol preventing vertical transmission (PPTV), and follow up of children to 18 months of age. RESULTS: Of 358 HIV-positive patients vertically infected, five women became pregnant, between 14 and 24 years old. Pregnancies were controlled in clinical/immune-stage N2 C3. They had received two to five therapies. Full PPTV was performed in all binomials. Pre-natal undetectable viral loads ranged from 4,700 ARN copies/mL. Five living children were born by Caesarean section, four of them with 37 weeks of completed gestation and one of them with 34 weeks of gestation. All received zidovudine (AZT) for 6 weeks. CD4 at 72 hours of life ranged from 48% to 74.6%. All children were born uninfected with HIV. Only two had mild anemia. CONCLUSIONS: Expectations of HIV mothers vertically infected to have healthy children are similar to those infected by horizontal transmission, using PPTV.

[Pott's disease and immunological diagnosis of tuberculosis, about a pediatric clinical case]. / Mal de Pott y diagnóstico inmunológico de tuberculosis, a propósito de un caso pediátrico.

UNLABELLED: Tuberculosis (TB) remains a major health problem in the world. The clinical forms of TB in children are variable, pulmonary involvement occurs in two thirds of cases. In the remaining third, clinical forms incluye node, meningeal and osteoarticular involvement. CASE REPORT: 7 year old boy with a history of an osteolytic lesion of the right ischial branch. Three months later he presented with spondylodiscitis at L2-L3, associated with a large abscess in the right iliac psoas muscle. Pott's disease was suspected, and tuberculin test and T-SPOT®.TB test were performed, with a positive result. Antimicrobial treatment was initiated with isoniazid, rifampicin, pyrazinamide and ethambutol. After 30 days, Mycobacterium tuberculosis was isolated from psoas abscess. We discuss methods of TB diagnosis, with special emphasis on immunological methods: tuberculin test and interferon-gamma release assays. Methods of immunological TB diagnosis are an important contribution to the diagnosis of this disease, allowing early initiation of treatment.

Mal de Pott y diagnóstico inmunológico de tuberculosis, a propósito de un caso pediátrico / Pott's disease and immunological diagnosis of tuberculosis, about a pediatric clinical case

Tuberculosis (TB) remains a major health problem in the world. The clinical forms of TB in children are variable, pulmonary involvement occurs in two thirds of cases. In the remaining third, clinical forms incluye node, meningeal and osteoarticular involvement. Case report: 7 year old boy with a history of an osteolytic lesion of the right ischial branch. Three months later he presented with spondylodiscitis at L2-L3, associated with a large abscess in the right iliac psoas muscle. Pott's disease was suspected, and tuberculin test and T-SPOT®.TB test were performed, with a positive result. Antimicrobial treatment was initiated with isoniazid, rifampicin, pyrazinamide and ethambutol. After 30 days, Mycobacterium tuberculosis was isolated from psoas abscess. We discuss methods of TB diagnosis, with special emphasis on immunological methods: tuberculin test and interferon-gamma release assays. Methods of immunological TB diagnosis are an important contribution to the diagnosis of this disease, allowing early initiation of treatment.

La tuberculosis sigue siendo un importante problema en salud en el mundo. Las formas clínicas de TBC en los niños son muy variadas, presentándose en dos tercios de los casos compromiso pulmonar. En el tercio restante destacan los compromisos ganglionar, meníngeo y osteoarticular. Caso clínico: varón de 7 años que presentó una espondilodiscitis L2-L3, asociada a un absceso en músculo psoas-ilíaco derecho. Por sospecha de mal de Pott se realizó PPD y T-SPOT®.TB que resultaron positivos. Se inició tratamiento antimicrobiano asociado con isoniazida, rifampicina, pirazinamida y etambutol. Después de 30 días, se aisló Mycobacterium tuberculosis del absceso del psoas. Se discute los métodos de diagnóstico de TBC en pediatría, con especial énfasis en los métodos inmunológicos: reacción de tuberculina y test de liberación de interferón-gamma, los que son una importante contribución para el diagnóstico de esta enfermedad, permitiendo el pronto inicio de su tratamiento.