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Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host.In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals—usually used off-label in paediatrics—to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring.The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population. Resumen: La monitorización terapéutica de antibióticos y antifúngicos en el paciente pediátrico, basada en parámetros farmacocinéticos y farmacodinámicos (PK/PD), es una estrategia cada vez más utilizada para la optimización del tratamiento de infecciones con el fin de mejorar la eficacia, reducir la aparición de toxicidades y prevenir la selección de resistencias antimicrobianas, especialmente en poblaciones vulnerables como neonatos, pacientes críticos o inmunodeprimidos.En la población neonatal y pediátrica, las infecciones representan un porcentaje elevado de los ingresos hospitalarios, siendo los antimicrobianos los fármacos más utilizados en este grupo poblacional. Sin embargo, establecer los regímenes posológicos óptimos en esta población es complejo debido a la menor evidencia respecto a la eficacia y seguridad de algunos antimicrobianos, especialmente en los de reciente comercialización que son utilizados habitualmente fuera de ficha técnica y al limitado número de estudios PK/PD disponibles en pediatría. Es bien conocido que el paciente pediátrico se caracteriza por presentar una serie de variaciones de los parámetros farmacocinéticos (como el aclaramiento o el volumen de distribución) debido a los propios cambios madurativos que pueden modificar la exposición a los antimicrobianos y comprometer el éxito del tratamiento. A su vez, es un grupo poblacional más susceptible a presentar potenciales efectos adversos a los fármacos, hecho que conlleva la necesidad de una monitorización más estricta.El objetivo de este documento de consenso, elaborado entre la Sociedad Española de Farmacia Hospitalaria (SEFH) y Sociedad Española de Infectología Pediátrica (SEIP), es describir la evidencia disponible sobre las indicaciones de la monitorización terapéutica de antibióticos y antifúngicos en pacientes neonatales y pediátricos, y proporcionar recomendaciones prácticas para su monitorización y ajuste de dosis, con el fin de optimizar el tratamiento, maximizando su eficacia y seguridad.

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient’s characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance.The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends. Resumen: La neutropenia febril es una de las principales complicaciones infecciosas que sufren los pacientes pediátricos oncohematológicos, y a pesar los avances en diagnóstico y tratamiento, siguen condicionando una mortalidad y morbilidad significativa. Estos pacientes agrupan una serie de factores de riesgo de infección, donde destaca la neutropenia asociada a quimioterapia, la disrupción de barreras cutáneo-mucosas y el uso de dispositivos intravasculares. El abordaje diagnóstico y terapéutico precoz de los episodios de neutropenia febril en los pacientes oncohematológicos, ajustado a las características individuales de cada paciente, es fundamental para mejorar su pronóstico. Por ello, diseñar protocolos de abordaje, que sistematicen su atención, permite optimizar y homogeneizar su abordaje. Además, racionalizar el uso de los antimicrobianos, ajustando la duración y el espectro de los mismos, es crucial para hacer frente al incremento de resistencias a antimicrobianos.El objetivo de este documento, elaborado entre la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Hematología y Oncología Pediátrica, es dar recomendaciones de consenso sobre el manejo de la neutropenia febril en el paciente oncohematológico, respecto al abordaje inicial, terapia secuencial y de soporte e infección fúngica invasiva, que cada centro debe adaptar a las características de sus pacientes y epidemiología local.

Introduction: Actions to reduce and optimize antimicrobial use are crucial in the management of infectious diseases to counteract the emergence of short- and long-term resistance. This is particularly important for pediatric patients due to the increasing incidence of serious infections caused by resistant bacteria in this population. The aim of this study was to evaluate the impact of a pediatric antimicrobial stewardship program (PROA-NEN) implemented in a Spanish tertiary hospital by assessing the use of systemic antimicrobials, clinical indicators, antimicrobial resistance, and costs. Methods: In this quasi-experimental, single-center study, we included pediatric patients (0–18 years) admitted to specialized pediatric medical and surgical units, as well as pediatric and neonatal intensive care units, from January 2015 to December 2019. The impact of the PROA-NEN program was assessed using process (consumption trends and prescription quality) and outcome indicators (clinical and microbiological). Antibiotic prescription quality was determined using quarterly point prevalence cross-sectional analyses. Results: Total antimicrobial consumption decreased during the initial three years of the PROA-NEN program, followed by a slight rebound in 2019. This decrease was particularly evident in intensive care and surgical units. Antibiotic use, according to the WHO Access, Watch and Reserve (AWaRe) classification, remained stable during the study period. The overall rate of appropriate prescription was 83.2%, with a significant increase over the study period. Clinical indicators did not substantially change over the study period. Direct antimicrobial expenses decreased by 27.3% from 2015 to 2019. Conclusions: The PROA-NEN program was associated with reduced antimicrobial consumption, improved appropriate use, and decreased costs without compromising clinical and/or microbiological outcomes in patients.

Cytomegalovirus (CMV) is a major cause of allogeneic hematopoietic stem cell transplant (HSCT)-related morbidity and mortality. Treatment failure continues to be a major issue in patients with CMV infection due to both drug resistance and intolerance. This single-center brief retrospective analysis of a case series aims to investigate the safety and efficacy of CMV-hyperimmune globulin as salvage therapy for CMV infection in children undergoing HSCT. Fifteen pediatric patients received human CMV-specific immunoglobulin (CMVIG) between July 2018 and December 2021 as a salvage therapy for refractory or recurrent CMV infection. At the time of CMVIG prescription, eight children presented with recurrent CMV infection and seven with refractory CMV infection. The overall response rate was 67% at 50 days from the CMVIG administration [95% confidence interval (CI): 44–88]. Overall survival (OS) from CMVIG administration at 100 days was 87% (95% CI: 56–96), and OS from HSCT at 1 year was 80% (95% CI: 50–93). Four patients died, three unrelated to CMV infection and one due to CMV pneumonia. CMVIG as salvage therapy was well tolerated, and no infusion-related adverse events were observed.

Abstract Background The increasing use of antifungal drugs (AF) in children and the concern for related adverse events and costs has led to the development of specific AF stewardship programmes (AFS). Studies in adult patients have shown improvements in AF prescription and usage after implementation, but paediatric data are scant. The aim of this PROAFUNGI study was to describe the use and appropriateness of AF in a high complexity paediatric centre. Methods Observational, prospective, single-centre, modified point-prevalence study (11 surveys, July–October 2018), including paediatric (

A previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly developed anisocoria. Computed tomography (CT) of the head showed fungal brain lesions. Urgent decompressive craniectomy with lesion drainage was performed; histopathology found hyphae in surgical samples, culture-positive for Aspergillus fumigatus (susceptible to azoles, echinocandins, and amphotericin B). Extension workup showed disseminated aspergillosis. After multiple surgeries and combined antifungal therapy (isavuconazole plus liposomal amphotericin B), her clinical course was favorable. Isavuconazole therapeutic drug monitoring was performed weekly. Extensive immunological study ruled out primary immunodeficiencies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) follow-up showed a gradual decrease in fungal lesions. Influenza-associated pulmonary aspergillosis is well-recognized in critically ill adult patients, but pediatric data are scant. Clinical features described in adults concur with those of our case. Isavuconazole, an off-label drug in children, was chosen because our patient had severe renal failure. To conclude, influenza-associated pulmonary aspergillosis is uncommon in children admitted to intensive care for severe influenza, but pediatricians should be highly aware of this condition to enable prompt diagnosis and treatment.

Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.