Convergence of Hypervirulence Determinants and Carbapenemase Genes in Klebsiella pneumoniae Depends on the Biomarker Definition: A Cross-Sectional Analysis of 131,090 Publicly Deposited Genomes

Carbapenem resistance and hypervirulence are reported to be converging in Klebsiella pneumoniae, but the reported frequency depends on how a hypervirulent genotype is defined. We analysed the NCBI Pathogen Detection Klebsiella organism group metadata (PDG000000012.2542, downloaded 6 October 2026) and included 131,090 K. pneumoniae genomes with an assembly and AMRFinderPlus output. Carbapenemase genes were assigned to families from pre-specified allele lists. The primary hypervirulence-associated genotype was at least four of the five biomarkers validated against a murine sepsis model (iucA, iroB, peg-344, rmpA, rmpA2); a permissive secondary definition (iucA and/or rmpA/rmpA2) and nine further definitions were analysed in parallel. Proportions are reported with Wilson 95% confidence intervals, and regression models with standard errors clustered on BioProject and on Pathogen Detection single-nucleotide polymorphism (SNP) cluster. A carbapenemase gene was present in 58.80% (95% CI 58.53–59.07) of genomes. Under the primary definition, 5.71% (5.59–5.84) of genomes carried the genotype and 1.03% (0.96–1.10) of carbapenemase-positive genomes were convergent, with no statistically detectable change in the odds per year of collection between 2010 and 2025 (odds ratio 0.99, SNP-cluster-clustered 95% CI 0.93–1.05); in this deposited sample the genotype was twelve times more common in carbapenemase-negative genomes (12.39%, 12.12–12.68). Under the secondary definition the corresponding figures were 24.59% and 28.18% (27.87–28.50), with an 18% rise in the odds per year (1.18, clustered 1.11–1.26), but 54.99% of the genomes it counted carried iucA alone. De-replication to one genome per SNP cluster halved the secondary-definition estimate to 13.70% (13.15–14.26) and left the primary one at 2.31% (2.08–2.57). Convergence estimates for this organism are therefore governed by the definition applied and by clonal redundancy in the archive. These are genotype frequencies in a convenience sample of deposited genomes, not population prevalences, and neither definition demonstrates the hypervirulent phenotype.