Antimicrobial resistance and hypervirulence in Klebsiella pneumoniae: a one health approach

Abstract Klebsiella pneumoniae is a gram-negative opportunistic bacterium and an important cause of hospital-acquired infections, including pneumonia, urinary tract infections, bloodstream infections, and surgical site infections. It is a member of the ESKAPE group and is considered a major global concern due to multidrug resistance (MDR) and hypervirulent strains. High prevalence of extended-spectrum β-lactamases (ESBLs), carbapenemases (KPC, NDM, OXA-48), and plasmid-mediated colistin resistance (mcr-1) has significantly restricted therapeutic options. Globally, K. pneumoniae accounted for nearly 790,000 infection-related deaths in 2019, ranking among the top causes of antimicrobial resistance-associated mortality. Epidemiological studies highlight resistance hotspots in Asia, Europe, and Latin America, with growing incidence in community and healthcare settings. The coexistence of MDR and hypervirulent lineages creates an unexpected clinical challenge, contributing to high morbidity, mortality, and healthcare costs. Pathogenesis is mediated by multiple virulence factors, including type 1 and type 3 fimbriae, capsular polysaccharides, siderophores, lipopolysaccharides, and biofilm formation, which promote adhesion, persistence, and immune evasion. Resistance mechanisms involve β-lactamase production, efflux pumps, porin mutations, lipid A modifications, plasmid-mediated resistance, and biofilm-associated tolerance. Advances in diagnostics, including MALDI-TOF, CRISPR-based assays, and AI-driven genomic analysis, offer rapid resistance detection and tailored therapy. Emerging treatments include novel antimicrobials (cefiderocol, plazomicin), phage therapy, antimicrobial peptides, CRISPR-mediated sensitization, and immune-based approaches, though clinical translation remains limited. Managing resistance and hypervirulent strains requires global and local action through antimicrobial stewardship, genomic surveillance, infection control, and One Health frameworks. An integrated strategy including innovative therapeutics, AI-driven precision medicine, and reasonable antibiotic use is essential to mitigate the growing threat of K. pneumoniae in the post-antibiotic era.