Antimicrobial stewardship programs (ASP) reduce the inappropriate use of antimicrobial agents. Traditionally, paediatric osteoarticular infections have been treated with prolonged intravenous antibiotics; however, evidence suggests that shorter intravenous therapy followed by oral narrow-spectrum antibiotics is effective. The aim of this study is to assess the impact of an ASP on the treatment of acute haematogenous bone and joint infections (AH-BJI) in children.We performed a single-centre quasi-experimental study comparing antibiotic use in paediatric [0–18 years] inpatients with AH-BJI before (2015–2016 period 1 [P1]) and after (2017-june 2023 period 2 [P2]) the implementation of a multifaceted hospital ASP with post-prescription review with feedback as the primary strategy. ASP also promoted a first-line empiric antibiotics change in the local protocol in June 2020. The study describes and compares the demographic and clinical characteristics among patients who were recruited prospectively during their hospital admission or in outpatient clinics. The primary outcomes were the length of antibiotic therapy, length of hospital stay, sequelae, readmission and fatality rates. Two-hundred-eighty-five patients were included (60 in P1 and 225 in P2). The length of parenteral antibiotic treatment and the length of hospital stay were significantly lower in P2 (median [IQR] days, P1: 8.5[7.0–12.0] vs P2: 7[4.5–8.0], p < 0.001; and P1: 8.5[7.0–11.0] vs P2: 7[5.0–9.0], p < 0.001, respectively). After June 2020, 3rd generation cephalosporin use decreased in patients < 5 years old (96/119[81%] vs 6/57[10%] cases; p < 0.001). The rates of sequelae, readmission (2/60[3.3%] in P1 and 8/225[3.6%] in P2) and mortality remained unchanged. Conclusion: After ASP implementation, the length of parenteral antibiotic treatment, length of hospital stay, and 3rd generation cephalosporin use in children with AH-BJI were reduced safely. What is Known:• Antimicrobial Stewardship Programmes (ASPs) have been shown to be effective for optimising antibiotic prescriptions and reducing antimicrobial resistance. There is still limited literature about ASPs in the paediatric population.• Paediatric bone and joint infections were traditionally treated with prolonged intravenous antibiotics. However, current evidence suggests that shorter intravenous therapy followed by oral narrow-spectrum antibiotics is equally effective. What is New:• Implementing an ASP with post-prescription review with feedback as main strategy, in a tertiary paediatric hospital, safely reduced the duration of intravenous treatment and length of hospital stay for children with acute haematogenous bone and joint infections (AH-BJI).• The ASP helped to reduce the use of 3rd generation cephalosporin in children with AH-BJI.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants 3 mg/L and 11.6–26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on C_max values, but a larger INH AUC_0–24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.

Background: Inappropriate antibiotic use contributes to antimicrobial resistance. Evidence regarding the impact of antimicrobial stewardship programs (ASPs) in pediatric intensive care units (PICUs) remains limited. The study aims to evaluate the impact of a multidisciplinary prospective post-prescription review and feedback (PPRF) ASP in a European PICU on antimicrobial use and prescription quality (PQ). Methods: A prospective quasi-experimental study was conducted using interrupted time-series analysis to evaluate antimicrobial use trends before (July 2018–December 2020) and after (January 2021–March 2025) the implementation of a multifaceted ASP, integrated within a hospital-wide ASP, in a tertiary 24-bed medical–surgical PICU in Barcelona, Spain. Antimicrobial use was measured as days of therapy per 100 patient-days (DOT/100 PD) and per 100 discharges (DOT/100 D) and was analyzed by WHO AWaRe group and by individual drug. PQ was evaluated by means of cross-sectional point-prevalence surveys (PPSs). Results: During the study-period, median monthly activity in the PICU remained stable: 475 patient-days (IQR: 396–534) and 113 patients discharged (IQR: 102–124). Following ASP implementation, total antibiotic consumption significantly decreased, with an immediate reduction of 18.2 DOT/100 patient-days (p = 0.006) and a sustained monthly decline of 0.73 DOT/100 patient-days (p = 0.028). The COVID-19 pandemic did not significantly affect overall antibiotic consumption. Access and Reserve antibiotic use decreased significantly after ASP implementation, whereas Watch antibiotic use remained unchanged. Overall antifungal consumption was not significantly modified, although a transient increase was observed during the pandemic. At the individual drug level, several antibiotics demonstrated significant immediate decreases after ASP implementation. Prescription quality remained high (>88% optimal prescriptions), and PICU length of stay and mortality were unchanged. Conclusions: Implementation of a multidisciplinary PPRF-based ASP in a tertiary PICU was associated with a sustained reduction in antibiotic exposure without compromising prescription quality or clinical safety. These data support the effectiveness of collaborative stewardship in one of the most complex pediatric healthcare settings.

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Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. Methods: We aimed to characterize the pharmacokinetics of a licensed INH suspension (10 mg/mL, Pharmascience Inc., Montreal, QC, Canada) in children receiving INH daily at 10 mg/kg in a single-center, open-label, non-randomized, phase IIa clinical trial (EudraCT Number: 2016-002000-31) in Barcelona (Spain). Samples were analyzed using a validated UPLC-UV assay. The N-acetyltransferase 2 gene was examined to determine the acetylation status. A non-compartmental pharmacokinetic analysis was conducted. Results: Twenty-four patients (12 females) were included (primary chemoprophylaxis, n = 12; TB treatment, n = 9; and TB infection preventive treatment, n = 3). The acetylator statuses were homozygous fast (n = 3), heterozygous intermediate (n = 18), and homozygous slow (n = 2; unavailable in one patient). The INH median (IQR) C_max and AUC_0–24h values were 6.1 (4.5–8.2) mg/L and 23.0 (11.2–35.4) h∙mg/L; adult targets (>3 mg/L and 11.6–26.3 h∙mg/L) were not achieved in three and six cases, respectively. Gender, age at assessment (2 years), and INH monotherapy (vs. combined TB treatment) had no impact on pharmacokinetic parameters. Significant differences in C_max (p = 0.030) and AUC_0–24h (p = 0.011) values were observed based on acetylator status. Treatment was well tolerated, and no severe adverse events were observed; three patients developed asymptomatic mildly elevated alanine aminotransferase levels. Conclusions: In infants and children receiving a daily INH suspension at 10 mg/kg, no safety concerns were raised, and the target adult levels were reached in the majority of patients.