[Clinical risk factors and molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infection].

Objective: To investigate the molecular epidemiological characteristics, antimicrobial resistance mechanisms, and clinical risk factors for infection with carbapenem-resistant Klebsiella pneumoniae (CRKP), and to examine the relationship between antimicrobial resistance and virulence. Methods: A total of 528 Klebsiella pneumoniae (KP) isolates and corresponding clinical data were collected from hospitalized patients at Qingdao Municipal Hospital between November 2016 and October 2023. Based on antimicrobial susceptibility testing results, 80 patients with CRKP infection were assigned to the CRKP group. Patients with carbapenem-susceptible K. pneumoniae (CSKP) isolates recovered within 7 days before or after the CRKP isolation date were selected as matched controls for each patient in the CRKP group. If insufficient eligible controls were available, the matching window was expanded to 30 days before or after the isolation date. Ultimately, 160 matched patients were included in the CSKP group. Whole-genome sequencing was performed on all included isolates to systematically characterize their molecular epidemiological features and resistance and virulence gene profiles. A multivariable logistic regression model was used to identify independent risk factors for CRKP infection. Spearman rank correlation analysis was performed to assess the correlation between resistance and virulence gene scores. Results: Multivariable logistic regression analysis showed that a history of antimicrobial agent use in the 30 days before infection (OR=4.411, 95%CI: 1.749-11.128; Wald χ²=9.882; P<0.01) and invasive abdominal procedures in 30 days before infection (OR=6.846, 95%CI: 3.141-14.922; Wald χ²=23.411; P<0.01) were independent risk factors for CRKP infection. ST11 was the predominant sequence type among CRKP isolates (80.0%), and the blaKPC-2 gene was the predominant resistance determinant (88.8%). The predominant CRKP clone, ST11, underwent a serotype transition from ST11-K25/O5 to ST11-K64/O2a. At the overall population level, the antimicrobial resistance gene score was negatively correlated with the virulence gene score (Spearman ρ=-0.321, P<0.001). However, subgroup analysis showed no significant correlation between the two scores within the same ST11 clone (Spearman ρ=0.020, P=0.872). These findings suggest that the overall negative correlation was a population-level artifact caused by inherent phenotypic differences among distinct clonal groups, rather than an evolutionary trade-off in which the acquisition of antimicrobial resistance within the same clone resulted in reduced virulence. The intensive care unit (ICU) was the central hub for nosocomial clonal transmission of CRKP. The predominant clone may have disseminated from the ICU to general wards through patient transfers, healthcare workers, or medical equipment, thereby forming interdepartmental transmission chains. Conclusions: A history of antimicrobial agent use and invasive abdominal procedures in the 30 days before CRKP infection were independent risk factors for CRKP infection. CRKP isolates frequently carried plasmids coharboring multiple antimicrobial resistance determinants and exhibited extensive antimicrobial resistance.