Ceftazidime-avibactam as a polymyxin-sparing option for multidrug-resistant Gram-negative infections in children: a real-world comparative cohort study

Multidrug-resistant (MDR) Gram-negative infections are challenging to treat in children, and polymyxin-based regimens are limited by toxicity. We evaluated the real-world use of ceftazidime-avibactam (CZA) as a potential polymyxin-sparing option for children with MDR Gram-negative infections. We conducted a single-center retrospective comparative cohort study at a tertiary hospital in Istanbul, Türkiye. Children aged < 18 years who received definitive therapy for microbiologically confirmed MDR Gram-negative infections between January 2022 and May 2024 were included. The primary outcome was 28-day all-cause mortality. Secondary outcomes included clinical response, documented microbiological clearance, acute kidney injury (AKI), drug-induced liver injury (DILI) and one-year all-cause mortality. Forty-five children were included: 15 received CZA-based therapy and 30 received non-CZA regimens. Mechanical ventilation was required in 40/45 (88.9%) patients, reflecting a critically ill cohort. Steroid exposure within 30 days (46.7% vs. 6.7%; P = 0.003) and prior carbapenem exposure (93.3% versus 56.7%; P = 0.016) were more frequent in the CZA group. Clinical response (73.3% versus 73.3%; P = 1.000) and 28-day all-cause mortality (40.0% versus 40.0%; P = 1.000) were comparable between groups. Documented microbiological clearance, AKI and DILI did not differ significantly. Similar findings were observed in the CZA vs. meropenem plus colistin subgroup. CZA-based therapy showed similar observed outcomes and no clear excess toxicity signal compared with heterogeneous non-CZA regimens, despite preferential use in children with greater recent antimicrobial exposure and clinical complexity. These findings support CZA as a feasible polymyxin-sparing option in selected children.