Emerging Threats: Genomic Insights and Clinical Implications of Carbapenem-Resistant K. pneumoniae

A genomic analysis of 99 carbapenem-resistant Klebsiella pneumoniae isolates documents a shifting clonal landscape: ST11 remains dominant (63.6%, 63/99), while an emergent clone, ST859, accounts for 15.2% (15/99)—a shift that changes bedside resistance expectations.

Clinically relevant resistance differences were evident. ST859-KL19 demonstrated higher resistance to tetracyclines and colistin than ST11 and more frequently carried tet(A), qnrS variants, and LAP-2. Enzyme profiling identified KPC-2 as the predominant carbapenemase with frequent CTX-M-65 ESBL co-occurrence; roughly three-quarters of isolates co-harbored carbapenemase and ESBL genes, a resistance signature that supports capsular and sequence-type surveillance.

Conjugative plasmids were central to the genomic picture. The team reconstructed 367 plasmids across the collection, finding IncF replicons most prevalent and 60 conjugative plasmids—most (52/60) IncFII—with 56/60 carrying antibiotic-resistance genes including KPC-2 and TEM variants. Predicted host range clustered in Enterobacterales, and these mobile elements offer a parsimonious explanation for rapid interstrain acquisition of carbapenemase and ESBL determinants. Plasmid profiling therefore clarifies transmission pathways and complements sequence typing for outbreak detection.

Therapeutic implications follow from clone-level resistance differences. Rising ST859-KL19 prevalence predicts higher local rates of colistin non-susceptibility and tetracycline resistance, narrowing salvage options despite preserved tigecycline activity (100% susceptibility in this collection) and substantial but incomplete activity of ceftazidime/avibactam (~78.8% susceptible). KPC-2 remains the dominant carbapenemase, preserving the potential role of KPC-targeted agents where available; these impacts should be interpreted alongside local antibiograms and rapid phenotypic testing to refine empiric and targeted choices.

Key Takeaways:

• ST11 remains predominant (63.6%), while ST859-KL19 is an emergent second-line clone (15.2%) with higher tetracycline and colistin resistance—a clear shift in the resistance landscape.
• Acute-care wards and ICUs, patients with heavy prior antibiotic exposure, and reference-laboratory surveillance programs are most likely to encounter these clone-level differences in clinical isolates.
• Expand multicenter genomic surveillance, integrate capsular typing into reference workflows, and prioritize robust phenotypic colistin testing for regional programs.