Risk factors, clinical outcomes of patients with Ceftazidime/Avibactam-resistant carbapenem-Resistant Klebsiella pneumoniae infection and its potential resistant mechanisms

BACKGROUND: Ceftazidime/avibactam (CZA) resistance (CZAr) poses critical challenges for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. The early identification of high-risk populations is essential for controlling nosocomial transmission and guiding empirical therapy. This study aimed to systematically focus on the correlation between the clinical characteristics of patients and the microbial features of CZArCRKP. METHODS: We conducted a retrospective cohort study (January 2020-May 2023) of 97 patients with CRKP infection. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were used to analyze resistance phenotype-genotype correlations. Survival outcomes were evaluated using Kaplan-Meier analysis. RESULTS: CZArCRKP primarily caused lower respiratory (72.16 %) and urinary tract (16.49 %) infections, predominantly affecting elderly patients with comorbidities (81.4 %) or undergoing invasive procedures (63.9 %). Chronic renal failure combined with platelet counts > 149× 10⁹/L post-infection strongly predicted patients with CZArCRKP in pulmonary infections. NDM-1 gene carriage and OmpK36 mutations were associated with CZA resistance. CZA-treated patients demonstrated lower 14-day mortality rates. CONCLUSION: We established the first integrated host-pathogen risk model for CZArCRKP and identified chronic renal failure and platelet count as key clinical predictors. NDM-1/OmpK36 mutations represents a clear mechanism of resistance. CZA use may improve the survival of selected patients with CRKP. These findings advance the surveillance and therapeutic strategies for multidrug-resistant infections.