Valentina Gutiérrez

Respiratory syncytial virus (RSV) remains a leading cause of infant lower respiratory tract infection, hospitalization, and death in Latin America and the Caribbean, where unequal access to diagnosis, medical care, oxygen, referral, and intensive care worsens outcomes. New passive immunization tools, maternal RSV prefusion F vaccination and long-acting monoclonal antibodies, can protect infants before peak vulnerability. Still, their population impact depends on timing, coverage, equity, financing, surveillance, and program design. Emerging regional experience with hybrid strategies may help close protection gaps among infants missed or insufficiently protected by maternal immunization. Severe early-life RSV disease is consistently associated with recurrent lower respiratory tract infections, wheezing, asthma, impaired lung-function trajectories, and increased health-care use. However, causality and long-term effects of current preventive products remain uncertain. A regional agenda linking maternal-infant cohorts, surveillance, equity analyses, and life-course economic evaluation is needed to define the full public health value of RSV prevention.

Background/Objectives: The objective of this study is to evaluate the efficacy and safety of maintaining antimicrobial (AM) therapy or adjusting AM therapy during episodes of febrile neutropenia (FN) catalogued as a fever of unknown origin (FUO) in children with cancer. Methods: This is a prospective, multicenter, noninferiority, randomized study, approved by ethics committee, in children with episodes of FN in eight hospitals in Chile. Microbiological and molecular samples were drawn at admission. Patients with FUO (negative bacterial and viral study with no clinical focus suggesting infection) and favorable evolution during the first 48–72 h of AM therapy were randomized 1:1 to maintain or adjust treatment, reducing the number and spectrum of AMs. The primary endpoint was the percentage of episodes with an uneventful resolution; the secondary endpoints were the re-adjustment of AM therapy, days of fever/hospitalization/AM therapy, days of vancomycin and meropenem per 1000 days of neutropenia, number of AMs after randomization, pediatric intensive care unit (PICU) admission, sepsis, and death. Results: A total of 266 of 939 FN episodes recruited between March 2021 and January 2024 were catalogued as FUO, of which 231 had a favorable evolution at 48–72 h and were randomized, 111 to maintain and 120 to adjust AM therapy. Both groups presented the same percentage of uneventful resolution, with 106 (96%) in the group that maintain AM therapy and 114 (95%) in the adjusted group (p = 1.00); relative risk 1.01, (95%CI 0.95–1.06); absolute risk difference 0.01, (95%CI −0.05–0.06). Conclusions: The main finding of this study demonstrates that adjusting antimicrobial therapy appears safe in carefully selected FUO cases with a favorable early evolution, during episodes of FN catalogued as FUO in children with cancer. These findings open an opportunity to new AM stewardship strategies in this population, with a possible future impact on AM resistance.

Isavuconazole is increasingly being used for the treatment of invasive fungal disease (IFD), although real-world pediatric data remain limited. We retrospectively reviewed patients aged ≤18 years who received isavuconazole for fungal infection at two tertiary centers in Chile between 2021 and 2025. Twenty patients were included, with a median age of 13.7 years (IQR, 9.4–15.5); 14 (70%) had an underlying malignancy, and 6 (30%) were allogeneic hematopoietic cell transplant recipients. Isavuconazole was used for treatment in 16 patients and for prophylaxis in 4, predominantly as second-line therapy due to prior antifungal intolerance, inadequate response, drug–drug interactions, or QT prolongation. Fifteen patients had IFD, with Mucorales (n=3) being the most frequently identified pathogens in proven cases and pulmonary involvement predominating in probable IFD. A succesful response at 90 days was achieved in 60% (6/10) of evaluable cases. No breakthrough fungal infections occurred during treatment or prophylaxis. Hepatic enzyme elevations were observed in four patients. Isavuconazole was associated with favorable outcomes and an acceptable safety profile, supporting its use as an alternative antifungal in pediatric patients.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and mortality in immunocompromised pediatric patients. This is a multicenter prospective cohort study with a nested retrospective analysis aimed at identifying risk factors for IFD in immunocompromised children with cancer and episodes of persistent high-risk febrile neutropenia (HRFN). One hundred and seventy-four episodes of persistent HRFN were analyzed, of which 34 (19.5%) were confirmed as IFD, 52.9% were caused by filamentous fungi, and 47.1% by yeasts. Logistic regression and survival analyses identified the following significant risk factors for IFD: male sex (OR 4.04), adolescence (OR 4.65), C-reactive protein ≥ 90 mg/L at admission (OR 3.13), and transfer to a critical care unit (OR 10.73). The predictive model demonstrated strong discriminatory capacity (AUC 0.84), with 79.4% sensitivity and 82.1% specificity. These findings highlight that adolescents, particularly males with severe clinical conditions and elevated inflammatory markers, are at the highest risk for IFD during episodes of HRFN. The proposed risk factor-based model may support early risk stratification and guide targeted antifungal prophylaxis or therapy, potentially improving outcomes in this population. Validation an external cohort is required to confirm these results and optimize clinical applicability.

Interleukin‐33 (IL‐33) is an IL‐1 family cytokine that activates various immune cells and induces both systemic and localized Th2 responses during infection. An association between IL‐33 and its suppresion of tumorigenicity 2 (ST2) receptor with inflammation during respiratory tract infection has been previously reported. Furthermore, some data suggest that during respiratory infections, IL‐33 may serve as an indicator of disease severity, as high levels of this cytokine have been found in nasopharyngeal swab (NPS) samples of infants with lower respiratory tract disease caused by respiratory syncytial virus (RSV). As viral diagnosis is mostly compartmentalized in NPS, in this report, we aimed at detecting IL‐33 in NPS from patients with respiratory tract infections that were collected in two different transport media (universal transport medium [UTM], and phosphate‐buffered saline [PBS]). IL‐33 levels were evaluated in 230 NPS samples, 121 obtained in PBS, and 109 in UTM. The samples were tested for RSV, metapneumovirus, adenovirus (ADV), influenza, and parainfluenza. In this cohort, higher levels of IL‐33 were detected in virus‐positive samples collected in PBS compared to virus‐negative samples collected in the same transport medium. In addition, RSV‐ and FLU‐positive samples collected in PBS showed higher measured IL‐33 levels than those collected in UTM. No significant differences were found for the other viruses included in this study. These findings highlight the importance of considering sample collection and transport conditions when interpreting IL‐33 measurements in NPS, particularly in future studies evaluating IL‐33 as a potential severity‐associated biomarker during RSV or influenza infection.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and mortality in immunocompromised pediatric patients. This is a multicenter prospective cohort study with a nested retrospective analysis aimed to identify risk factors for IFD in immunocompromised children with cancer and episodes of persistent high-risk febrile neutropenia (HRFN). One hundred and seventy-four episodes of persistent HRFN were analyzed, of which 34 (19.5%) were confirmed as IFD, 52.9% caused by filamentous fungi and 47.1% by yeasts. Logistic regression and survival analyses identified the following significant risk factors for IFD: male sex (OR 4.04), adolescence (OR 4.65), C-reactive protein ≥ 90 mg/L at admission (OR 3.13), and transfer to a critical care unit (OR 10.73). The predictive model demonstrated strong discriminatory capacity (AUC 0.84), with 79.4% sensitivity and 82.1% specificity. These findings highlight that adolescent, particularly males with severe clinical conditions and elevated inflammatory markers, are at highest risk for IFD during episodes of HRFN. The proposed risk factors-based model may support early risk stratification and guide targeted antifungal prophylaxis or therapy, potentially improving outcomes in this population. Validation in external cohort is required to confirm these results and optimize clinical applicability.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac^® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac^®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac^® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Palabras clave: infección fúngica invasora; neutropenia febril; profilaxis antifúngica

La infección del tracto urinario (ITU) es una de las infecciones bacterianas más frecuentes en la infancia. Un adecuado diagnóstico es esencial para poder realizar un tratamiento racional, eficiente y eficaz; sin embargo, existe gran heterogeneidad en los métodos diagnósticos, específicamente en el estudio de la susceptibilidad antimicrobiana. El objetivo de estas recomendaciones es entregar herramientas para uniformar los criterios diagnósticos, el estudio de susceptibilidad bacteriana in vitro y el tratamiento antimicrobiano de la ITU en la población pediátrica, con un enfoque de uso racional de los antimicrobianos. En esta primera parte, se presentan las recomendaciones en cuanto a cómo obtener una adecuada muestra de orina, el diagnóstico de laboratorio incluyendo puntos de corte –unidades formadoras de colonias/mL de orina–, además de consideraciones microbiológicas para el estudio de susceptibilidad y finalmente, el manejo de la ITU en pediatría. En la segunda parte se detalla el tratamiento antimicrobiano de sus complicaciones, el manejo de ITU en situaciones especiales y consideraciones farmacocinéticas y farmacodinámicas de los antimicrobianos a indicar en ITU.

La infección del tracto urinario (ITU) es una de las infecciones bacterianas más frecuentes en la infancia. Un adecuado diagnóstico es esencial para poder realizar un tratamiento racional, eficiente y eficaz; sin embargo, existe gran heterogeneidad en los métodos diagnósticos, específicamente en el estudio de la susceptibilidad antimicrobiana. El objetivo de estas recomendaciones es entregar herramientas para uniformar los criterios diagnósticos, el estudio de susceptibilidad bacteriana in vitro y el tratamiento antimicrobiano de la ITU en la población pediátrica, con un enfoque de uso racional de los antimicrobianos. En la primera parte, se presentaron las recomendaciones en cuanto a cómo obtener una adecuada muestra de orina, el diagnóstico de laboratorio incluyendo puntos de corte-unidades formadoras de colonias/mL de orina-, además de consideraciones microbiológicas como estudio de susceptibilidad y finalmente, el manejo de la ITU en pediatría. En esta segunda parte se detalla el tratamiento antimicrobiano de sus complicaciones, el manejo de ITU en situaciones especiales y consideraciones farmacocinéticas y farmacodinámicas de los antimicrobianos a indicar en ITU.