Post-neurosurgical infections caused by multidrug-resistant Enterobacterales are difficult to treat due to limited therapeutic options. Ceftazidime-avibactam (CAZ-AVI), a combination of cephalosporin and a novel β-lactamase inhibitor, has exhibited potential activity against multi/extensive drug-resistant (MDR/XDR) gram-negative bacilli. Several reports have described the successful treatment of central infections caused by MDR/XDR Pseudomonas aeruginosa or Enterobacterales. However, data on the efficacy and effective drug distribution of CAZ-AVI in the central nervous system (CNS), particularly in children, are lacking. We report a case of a 4-year-old girl with post-neurosurgical meningitis and abscess caused by extended-spectrum β-lactamase-producing Escherichia coli successfully treated with CAZ-AVI. CAZ-AVI therapeutic drug monitoring was performed to evaluate its efficacy and effective drug distribution in the CNS. We measured CAZ (15.6, 7.1, and 3.5 μg/mL) and AVI (4.0, 2.1, and 1.2 μg/mL) in cerebrospinal fluid (CSF) samples obtained 3, 5, and 7 h after the administration of the 15th CAZ-AVI dose (2.5 g, q8h, iv), respectively. We also measured CAZ (57.0 and 25.8 μg/mL) and AVI (11.3 and 4.5 μg/mL) in serum samples obtained 3 and 5 h after the administration, respectively. CAZ-AVI achieved an adequate CSF concentration throughout the drug interval. Our case provides evidence for using CAZ-AVI to treat CNS infections.