Objective  To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Methods  A retrospective analysis was conducted on clinical data from patients screened for carbapenem-resistant Enterobacteriaceae(CRE) at the First Affiliated Hospital of Kunming Medical University between January 2023 and December 2024. For patients identified with intestinal colonization of CRKP via rectal swab samples, subsequent occurrences of secondary bloodstream infections were monitored. Paired analysis was performed comparing the intestinal colonizing strains with the bloodstream infection strains in cases where bacteremia occurred. Antimicrobial susceptibility testing, biofilm formation capacity, siderophore quantification, and serum resistance assays were conducted to compare phenotypic differences in drug resistance and virulence between colonizing and invasive strains. Whole-genome sequencing was applied to assess genetic homology.

Results  Among 12 878 patients screened for CRE, 60 (0.47%) were identified with intestinal CRKP colonization. Of these, 6 (10.0%) developed bloodstream infections, with an all-cause mortality rate of 66.7% (4/6) during hospitalization. The predominant strain type among paired isolates was ST11-KL64 producing KPC-2, accounting for 91.7%(11/12) of cases. Except for one patient(with a categorical agreement of 82.6%), colonizing and bloodstream isolates from the same patient showed complete agreement (100% categorical agreement) in antimicrobial susceptibility profiles for all antibiotics except tigecycline. Intraclass correlation coefficients for biofilm formation and siderophore production were both > 0.75 of all paired strains, indicating high phenotypic consistency. Except for one patient, core genome single nucleotide polymorphism (SNP) analysis and phylogenetic reconstruction revealed high genetic homology between colonizing and bloodstream isolates from the same patient (SNP difference < 10). Clonal relatedness was also observed among colonizing strains from different departments (SNP difference < 120).

Conclusions  Although the intestinal colonization rate of CRKP is low, it poses a high mortality risk once bloodstream infection occurs. The high consistency in antimicrobial resistance profiles, biofilm formation, siderophore production, and genomic homology between colonizing and bloodstream isolates suggests that intestinal colonization is the direct source of subsequent invasive infection. Enhanced early screening, dynamic monitoring, risk-stratified prevention, and optimized intervention strategies are recommended to reduce the risk of CRKP infection and mortality.