Abstract: OBJECTIVE To explore the antibacterial therapy of ceftazidime/avibactam-resistant Klebsiella pneumoniae strains in vitro and to provide a basic theory for the clinical treatment against such resistant strains. METHODS The possible resistance genes of two Klebsiella pneumoniae strains were characterized by PCR, and then the amplicons were sequenced. The effect of monotherapy and combination of the different antibiotics against the resistant strains were evaluated by in vitro time-kill experiments. RESULTS Deficiency of outer membrane porins and production of metallo-beta-lactamase mediated the two strains to ceftazidime/avibatan-resistant, respectively. The time-kill experiment results showed that monotherapy and two-drug combinations of polymyxin B, imipenem, meropenem and fosfomycin could not obtain a satisfactory bactericidal effect. However, the triple therapy of polymyxin B-meropenem-fosfomycin or polymyxin B-ceftazidime-averbactam could produce strong and sustained bactericidal effect on the two drug-resistant strains respectively. CONCLUSION Different triple therapy based on polymyxin B may be an effective strategy against ceftazidime/avibactam-resistant Klebsiella pneumonia strains underlying a different resistant mechanism.