Effectiveness and Safety of Ceftazidime-Avibactam in the Paediatric population: interim analysis of prospective observational study – ESCAPE study

Introduction: The spread of multidrug-resistant (MDR) Gram-negative bacteria poses a significant global threat to public health in adults and in children. Infections due to carbapenem-resistant Enterobacterales (CRE) are associated with poor clinical outcomes, especially in critically ill patients. Ceftazidime/avibactam (CAV/AZI) is one of new β-lactam/β-lactamase molecules (BLIC) and recently approved for children. The real-world impact in paediatric population is still unclear and our study aims evaluating the effectiveness and safety of ceftazidime/avibactam in children. Method: This is a multicentre, prospective observational study including six Italian paediatric centres. We enrolled patients from 3 months to 18 years admitted to hospital with a documented or suspected gram-negative infection. We collected demographic and clinical baseline information (T0), and laboratory tests and microbiological cultures taken after 5-7 days (T1) and T2 10-14 days (T2) after drug administration. The outcome assessment for infections related mortality and infections relapse was performed at 30 days after the last dose of CAZ/AVI (T3). A pharmacokinetic sample and analysis were performed in order to guarantee the achievement of steady-state and to evaluate the pharmacokinetic characteristics. Results: 45 children were included in the analysis, with a mean age of 5.6 years. Most of them had comorbidities (88.9%), mainly chronic heart disease (36.4%), chronic lung disease (29.5%), and chronic kidney disease (15.5%) diseases. Initial symptoms involved fever (64.4%) and respiratory symptoms (49.2%). Pathogens were identified primarily in broncho-alveolar lavage (31.1%) and in blood (22.2%) samples, with significant positivity for MDR bacteria, including 22.6% CRE (K. pneumoniae NDM, KPC and OXA-48 and P. aeruginosa VIM). Ceftazidime/avibactam was used as a second- or third-line therapy in 73.3% of cases, with concurrent antibiotics administered in 64.4% cases. At 7 days post-treatment initiation, clinical improvements and decreased inflammation markers were undelighted. Infection recurrence was observed in 8 cases, linked to intensive care unit admission (p=0.0368) and polymicrobial therapy (p-value 0.0352). Mortality was 6.7%, with deaths attributed to underlying chronic conditions rather than infection. The pharmacokinetic analysis showed a At Pk T1, the mean concentration was 183.294 mg/L for ceftazidime and 13.231 mg/L for avibactam. Conclusion Our study supports the safety of CAZ/AVI in children and promising therapeutic outcomes. Further research with a larger sample size is needed to deepen insights into paediatric pharmacokinetics and pharmacodynamics.