The resistance mechanisms and risk factors of carbapenem-resistant Klebsiella pneumoniae to ceftazidime-avibactam

Objective To investigate the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP),elucidate the resistance mechanisms to ceftazidime-avibactam (CZA) and identify the risk factors associated with CZA resistance. Clinical and microbiological data from 293 hospitalized patients with CRKP infections were retrospectively collected at the First Affiliated Hospital of Xi'an Jiaotong University from January 2024 to March 2025. Based on CZA susceptibility results, patients were divided into the CZA-sensitive CRKP group (n = 228) and the CZA-resistant CRKP group (n = 64). The colloidal gold detection method was used to identify five carbapenemase genes( bla KPC, bla NDM, bla VIM, bla IMP, and bla OXA)and their subtypes were determined through PCR amplification and sanger sequencing. The relative expression of the bla KPC gene was measured using real-time quantitative PCR (RT-qPCR). Multivariate logistic regression analysis was performed to identify risk factors for CZA-resistant CRKP infections. Results The primary resistance mechanisms for CZA-resistant CRKP in our hospital are the production of metal enzymes, especially KPC-2 and NDM-1 co-producing strains. Some strains exhibit resistance to CZA due to blaKPC-2 mutations and increased gene expression. Multivariate logistic regression analysis revealed that renal replacement therapy ( OR  = 2.611, 95% CI 1.192–5.721) and prior CZA exposure ( OR  = 2.749, 95% CI 1.269 ~ 5.953) were independent risk factors for CZA-resistant CRKP infections.