Abstract: OBJECTIVE To investigate the in vitro combined antimicrobial susceptibility characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) with different carbapenemase types, with a focus on the subgroups of CRKP resistant to ceftazidime/avibactam (CZA), polymyxin B (PB) and those with mixed enzyme types, providing a basis for precise clinical treatment. METHODS A total of 147 CRKP strains isolated from Henan Provincial People's Hospital from Jan. to Dec. 2023 were collected. Among them, 123 strains were identified as K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP), 11 strains as New Delhi metallo-β-lactamase-producing KP (NDM-KP), and 13 strains as KPC-NDM-producing KP (KPC-NDM-KP) with the colloidal gold immunochromatography. Strains resistant to PB and CZA were particularly included. The combined effects of CZA and PB with drugs such as meropenem (MEM), aztreonam (ATM), imipenem (IPM) and tigecycline (TGC) were determined with the checkerboard microdilution method, and the fractional inhibitory concentration index (FICI) and susceptibility breakpoint index (SBPI) were calculated. RESULTS For KPC-KP: The synergistic rates of CZA combined with MEM, ATM and IPM (86.67%, 87.01% and 80.50%, respectively) were higher than those of CZA combined with amikacin (AMK) and TGC (P＜ 0.05), and the results for CZA-resistant CRKP were consistent with this. Among PB-resistant strains, the synergistic rate of PB combined with CZA was 54.00%, which was superior to other PB combination regimens (P＜ 0.05). For NDM-KP: The synergistic rate of CZA combined with ATM was 83.33%. For KPC-NDM-KP: The synergistic/additive rate of CZA combined with ATM was 100.00%. CONCLUSIONS The dual-index system of FICI and SBPI provides important experimental evidence for the precise treatment of multidrug-resistant CRKP infection. This study systematically elucidates, for the first time, the combined medication patterns for CZA/PB-resistant and mixed enzyme-type CRKP: for CZA-resistant KPC-KP, CZA combined with β-lactam drugs is recommended. For PB-resistant CRKP, the PB combined with CZA regimen is significantly superior to traditional combinations. For KPC-NDM-KP, CZA combined with ATM should be the first choice.