Multicenter Evaluation of Ceftazidime/Avibactam in Pediatric Patients Across the United States: Real-World Insights into the Management of Drug-Resistant Gram-Negative Infections.

BACKGROUND

Antimicrobial resistance among gram-negative pathogens is a global threat, with children particularly vulnerable due to limited treatment options and age-specific clinical outcomes data. Ceftazidime/avibactam (CZA) is effective against resistant gram-negative bacteria and demonstrates high success rates in adults; however, pediatric data remain limited. This study examined CZA use in children across United States medical centers.

METHODS

This multicenter, retrospective, observational cohort study included pediatric patients (<18 years) who received ≥48 hours of CZA for suspected or confirmed gram-negative infections between February 2015 and October 2023. The primary outcome was clinical success, defined as occurrence of all 3 components: (1) absence of all-cause mortality within 30 days of CZA initiation, (2) absence of microbiologic and clinical recurrence within 30 days of CZA discontinuation, and (3) resolution or improvement of infection-related signs and symptoms during CZA therapy without modification of therapy due to clinical failure. Secondary outcomes included adverse events attributable to CZA and resistance development to CZA.

RESULTS

One-hundred patients were included, with most receiving CZA for targeted therapy (67%). The median (IQR) age and weight were 9.8 (1.9-15.9) years and 24.2 (12.2-49.9) kg, respectively. Nearly all patients (88%) had comorbidities, 42% of patients were immunocompromised, and more than half were admitted to the intensive care unit at the time of index infection. Most infections originated from the respiratory tract (50%), followed by primary bloodstream infections (23%). Carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales were identified in 37% and 31% of patients, respectively. The most frequently administered CZA dosage regimen was 50 mg ceftazidime/kg/dose q8 hours, utilized in 44% of cases, with a median (IQR) treatment duration of 10.1 (6.7-15.7) days. Clinical success was achieved in 76% of patients, while no CZA-attributable adverse events were observed. CZA resistance emerged subsequently in 5% of cases.

CONCLUSIONS

CZA demonstrated favorable outcomes and safety in a diverse pediatric cohort with drug-resistant infections, supporting its role as a viable therapeutic option in high-risk pediatric populations.