# Resistance, Virulence, and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Causing Bloodstream Infections in Saudi Arabia

## TL;DR

This study examines carbapenem-resistant Klebsiella pneumoniae causing bloodstream infections in Saudi Arabia, revealing high resistance and specific genetic traits.

## Contribution

The study integrates genomic and phenotypic data to identify dominant high-risk CRKP clones and their resistance/virulence profiles in a specific geographic region.

## Key findings

- CRKP isolates showed universal resistance to imipenem and high resistance to β-lactams and fluoroquinolones.
- Genomic analysis revealed dominance of ST147 and ST2096 lineages, associated with specific carbapenemase genes and virulence traits.

## Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a major cause of bloodstream infections and poses serious challenges to clinical management because treatment options are limited. This study aimed to characterize antimicrobial resistance, virulence-associated features, and molecular epidemiology of CRKP bloodstream isolates using integrated phenotypic and genomic approaches. A total of 74 non-duplicate CRKP isolates were collected from bloodstream infections at three tertiary-care hospitals in Riyadh, Saudi Arabia, between 2022 and 2024. All isolates showed classical Klebsiella pneumoniae phenotypic characteristics, including intrinsic resistance to natural and aminopenicillins, and were classified as either multidrug-resistant (MDR) or extensively drug-resistant (XDR). Resistance to imipenem was universal, and resistance to other β-lactams and fluoroquinolones was high. Carbapenemase genes were detected in 96.0% of isolates using the GeneXpert® Carba-R assay, with blaOXA-48-like and blaNDM being most common. Whole-genome sequencing demonstrated predominance of Ambler class D carbapenemases, particularly blaOXA-232, with additional contributions from blaNDM-1 and blaNDM-5. Co-occurrence of carbapenemase genes was observed in a subset of isolates. Virulence analysis showed that 37.8% of isolates exhibited a hypermucoviscous phenotype, and more than half carried at least one virulence-associated determinant linked to capsule regulation or iron acquisition. In contrast, most isolates showed weak or no biofilm-forming capacity. Multilocus sequence typing revealed substantial genetic diversity but clear dominance of high-risk lineages, particularly ST147 and the emerging ST2096, both closely associated with blaOXA-232 and blaOXA-48-like genes. Capsular and O-antigen analysis showed a non-random distribution dominated by KL64 and O1/O2. Phylogenetic analysis was consistent with clonal expansion and suggested intra-hospital spread, with the intensive care unit serving as a key reservoir and dissemination to other wards. In conclusion, CRKP bloodstream infections in this setting are largely associated with a limited number of epidemic clones that combine extensive antimicrobial resistance with virulence-associated traits. These findings support the need for ongoing genome-based surveillance, strengthened infection control measures, and antimicrobial stewardship to limit the spread of high-risk K. pneumoniae lineages in healthcare settings.