Impatto di programmi di stewardship diagnostica e antibiotica nei reparti pediatrici e nel setting delle cure primarie

Antibiotics are among the most commonly prescribed drugs in children, both in inpatient and outpatient settings. The misuse of antibiotics is recognized as a major driver of the increasing global issue of antimicrobial resistance (AMR), which is considered as one of the ten global threats. Over the past two decades, numerous national and international interventions have been introduced to combat AMR. In 2007, the Infectious Diseases Society of America launched the concept of Antimicrobial Stewardship Programs (ASPs), coordinated efforts to optimize antibiotic use while preserving patient outcomes. More recently, ASPs have been complemented by diagnostic stewardship (DS), particularly during the COVID-19 pandemic, with the increased use of rapid testing. Despite their proven effectiveness, the implementation of ASPs in pediatrics remains limited, largely due to resource constraints, such as the lack of dedicated personnel and funding. Effective data collection is essential to monitor changes in antibiotic prescribing practices. Additionally, pediatric-specific metrics are necessary to accurately assess antibiotic use and ensure appropriate evaluation in this population. The aim of this thesis is to provide a comprehensive overview of the current state of ASPs and DS examining their impact across various settings in high-income countries (such as pediatric emergency departments, pediatric intensive care units, and outpatient settings), as well as in low- and lower-middle-income countries. Additionally, recognizing the importance of data collection and the inherent challenges in daily data gathering, the research focused on identifying the optimal method and timing for collecting metrics to evaluate the impact of ASP. Specifically, the study aimed to determine the best timing for data collection through Point Prevalence Surveys to accurately capture median annual antibiotic prescription rates. It also presents the outcomes of a multifaceted ASP implemented in the Department of Women’s and Children's Health at Padua University Hospital, detailing results achieved in the Pediatric Acute Care Unit and in more complex settings, such as the Pediatric Intensive Care Unit and the Hemato-Oncological Wards, with tailored ASPs adapted to each context. Given that evidence-based practice underpins most stewardship interventions, the research includes findings from two systematic reviews and meta-analyses used to develop recommendations for managing mild to moderate community-acquired pneumonia within the Italian intersociety consensus, and for COVID-19 treatment in alignment with WHO guidelines. Finally, this thesis evaluates the benefits and limitations of DS in reducing antibiotic prescriptions, highlighting that while PoCTs can support clinicians in patient management, their utility in specific contexts, such as fever in newborns, remains unclear. Additionally, a systematic review with meta-analysis has evaluated the diagnostic accuracy of a novel computational score (MMBV score) that combines C-reactive protein (CRP), TNF-related apoptosis-induced ligand (TRAIL), and interferon-γ-induced protein-10 (IP-10). This thesis demonstrates the effectiveness of ASPs in reducing antibiotic use across various pediatric settings, while highlighting critical knowledge gaps that need addressing. Although ASP implementation in hospitals is vital for reducing antibiotic consumption, establishing national and international ASP networks, particularly in LMICs, is essential to strengthen the global fight AMR. The outpatient setting, where antibiotic use is highest, must also be prioritized. In terms of DS, further rigorous studies are required to assess its effectiveness. Specifically, the clinical scenarios where PoCTs and MMBV can provide the greatest benefit need to be identified, enabling more precise diagnoses and treatment decisions.