Genomic insights into the convergence of antimicrobial resistance and hypervirulence-associated determinants in high-risk Klebsiella pneumoniae lineages in Egypt

Background: The global emergence of multidrug-resistant (MDR) Klebsiella pneumoniae poses a significant public health crisis, particularly in healthcare settings. This is an increasingly prominent threat, driven by the rise of high-risk lineages that combine antimicrobial resistance with hypervirulence-associated determinants, thereby severely limiting treatment options and complicating infection control. Methods: This study investigated 71 non-duplicate clinical K. pneumoniae isolates collected from patients at five hospitals in Alexandria, Egypt, between 2022 and 2024. Whole-genome sequencing, antimicrobial susceptibility testing, and hypermucoviscosity screening were performed. Genotypic resistance determinants, virulence-associated genes, multilocus sequence types (MLSTs), and capsular (K) and lipopolysaccharide (O) loci were characterised. In addition, concordance between genotypes and phenotypes was assessed. Additionally, to place the Egyptian isolates in a broader regional context, lineage-specific phylogenetic analyses of the predominant high-risk STs (ST101, ST147, and ST11) were conducted using publicly available genomes from Egypt, Africa, and the Middle East. Results: High-risk, internationally recognised sequence types dominated in this study, with ST101 (35.2%), ST147 (23.9%), and ST11 (12.7%) being the most predominant. These lineages frequently harboured carbapenemase genes, predominantly bla NDM-5 and bla OXA-48, with co-occurrence of both genes. Phylogenomic analysis also revealed regional dissemination and local expansion. A striking 87.3% of the isolates carried Carbapenemase genes, with bla NDM-5 and bla OXA-48 predominating. Extended-spectrum β-lactamase genes were identified in 83.1% of isolates, with bla CTX-M-15 detected in 67.6%. Genes associated with resistance to fluoroquinolones, aminoglycosides, and folate pathway inhibitors were widespread, indicating higher resistance profiles. Virulence-associated loci were highly prevalent, including yersiniabactin (88.7%), rmpA (23.9%), rmpA2 (54.9%), and the aerobactin (iuc ABCD ) cluster (53.5%). Remarkably, genotype-based resistance prediction showed high concordance with phenotypic antimicrobial susceptibility testing, with diagnostic sensitivity and specificity of 99.5% and 92.2%, respectively, with overall accuracy of 98.6%. Conclusions: Our results highlight the crucial role of integrated genomic surveillance and antimicrobial stewardship in monitoring MDR Klebsiella pneumoniae in Egyptian healthcare settings, reinforcing the need for global initiatives to combat antimicrobial resistance.