Distinct role of virulence and antimicrobial resistance on mortality within a large Klebsiella spp. cohort

Background. Klebsiella spp. is emerging in various clinical infections. However, the clinical, genomic and socio-economic characteristics of Klebsiella spp. have not been systematically characterized in high-risk regions. Methods. A six-year longitudinal cohort study was performed. The demographic information, permanent residence, medical insurance, underlying diseases, infection type and mortality at 14-, 28-, 90-day were collected. Sequence type (ST), plasmid replicons, antimicrobial resistance genes, virulence genes and phylogenetic relationships were identified by whole genome sequencing. Isolates carried any combination of rmpA, rmpA2, iroB, peg-344 and iucA were identified as hypervirulence (HV). Results. A total of 1628 cases and isolates were enrolled and the mortality in 14-, 28- and 90-day was 10.9%, 16.4% and 24.6%, respectively. Among the cases, 87.8% (1429/1628) were infected by Klebsiella pneumoniae (Kp), which represented significantly higher mortality rates compared to those infected by other subspecies at 14-day (12.0% vs 3.0%, P < 0.001), 28-day (17.6% vs 7.8%, P = 0.002) and 90-day (26.2% vs 12.7%, P = 0.001). Virulence factors were key determinants of short-term mortality, with the iroB (OR = 1.600) and a higher virulence score (OR = 1.182) as independent risk factors. In contrast, the IncR (OR = 1.738) and resistance score>1 (OR = 2.742) were closely associated with long-term mortality, highlighting the essential role of antimicrobial resistance. Although the prognosis varied across different STs, ST11 showed a great increase in 90-day mortality. Importantly, a novel variant, ST11-KL25 harboring bla _CMY , emerged and over half of its infections resulted in 90-day mortality. Conclusions . Virulence was a key determinant of short-term mortality, while antimicrobial resistance contributed to long-term mortality of the Klebsiella spp. cohort. Endemic ST11 and its new variants play an important role in increased mortality.