Ceftazidime-avibactam-based regimens for the treatment of central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae in a paediatric patient

OBJECTIVE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) central nervous system (CNS) infections are difficult to treat in children because effective and safe therapeutic options are limited. We report a paediatric case of CRKP meningitis successfully treated with ceftazidime-avibactam (CZA) combination with intraventricular polymyxin B (PMB). METHODS: A 9-y-old child with severe traumatic brain injury and multiple prior neurosurgical procedures developed CRKP meningitis. After pathogen identification, antimicrobial therapy was switched to CZA plus intraventricular PMB, and the ventriculoperitoneal shunt was externalized. Clinical outcomes, cerebrospinal fluid (CSF) parameters, microbiological clearance, and plasma and CSF concentration of CZA were monitored during treatment. RESULTS: After CRKP was identified, therapy was adjusted to CZA (62.5 mg/kg every 8 h, administered as a 2-h infusion) plus intraventricular PMB based on susceptibility results. Fever resolved within 3 d of CZA initiation. CSF cultures became negative, and CSF parameters gradually normalized. Neurological status improved, and the patient was transferred to a rehabilitation facility. Pharmacokinetic analysis showed blood-brain barrier penetration rates of 19.4% for ceftazidime and 29.9% for avibactam. CONCLUSIONS: This report adds to the limited pharmacokinetic/pharmacodynamic (PK/PD) evidence for ceftazidime-avibactam in paediatric CNS infections. It also supports the potential role of ceftazidime-avibactam combined with intraventricular polymyxin B as a therapeutic option for CRKP meningitis in children. Further studies are needed to optimize dosing strategies and evaluate long-term safety in the paediatric population.