OBJECTIVE Klebsiella pneumoniae (K. pneumoniae) is one of the most common bacteria in the hospital-acquired central nervous system (CNS) infections. Central nervous system infections caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with significant mortality rates and high hospital costs due to limited antibiotic treatment options. This retrospective study aimed to evaluate the clinical efficacy of ceftazidime-avibactam (CZA) for the treatment of CNS infections caused by CRKP. METHODS Twenty-one patients with hospital-acquired CNS infections caused by CRKP who received treatment with CZA for ≥ 72 hours were enrolled. The primary outcome was to assess the clinical and microbiology efficacy of CZA for the treatment of CNS infections caused by CRKP. RESULTS A high burden of comorbidity was discovered in 20 of 21 patients (95.2%). Most patients had a history of craniocerebral surgery and 17 (81.0%) of the patients were in the intensive care unit with a median APACHE II score of 16 (IQR 9-20) and SOFA score of 6 (IQR 3-7). Eighteen cases were treated by CZA-based combination therapies, while the remaining three cases were treated with CZA alone. At the end of the treatment, the overall clinical efficacy was 76.2% (16 of 21) with a bacterial clearance rate of 81.0% (17 of 21) and all-cause mortality of 23.8% (five of 21). CONCLUSIONS This study showed that CZA-based combination therapy is an effective treatment option for CNS infections caused by CRKP.