Antibiotic resistance in K. pneumoniae: perspectives, challenges, health risks, therapeutic approaches

Abstract

Klebsiella pneumoniae is an opportunistic Gram-negative pathogen of increasing global concern due to its expanding virulence potential and rapid acquisition of antimicrobial resistance. Traditionally associated with hospital-acquired infections such as pneumonia, urinary tract infections, and bloodstream infections, K. pneumoniae has evolved into a highly diverse species comprising classical (cKP), hypervirulent (hvKP), multidrug-resistant (MDR), and emerging carbapenem-resistant hypervirulent (CR-hvKP) variants. Its pathogenicity is driven by a wide array of virulence factors, including capsular polysaccharides, siderophores, fimbriae, lipopolysaccharides, and multiple secretion systems, all of which facilitate immune evasion, tissue invasion, biofilm formation, and environmental survival. Parallel to this, K. pneumoniae has developed extensive resistance through intrinsic mechanisms, such as efflux pumps and porin alterations, as well as acquired determinants including ESBLs, carbapenemases (KPC, NDM, and OXA-48), 16S rRNA methyltransferases, and plasmid-mediated mcr genes conferring colistin resistance. These combined traits have led to widespread dissemination of MDR and XDR strains, limiting therapeutic options and contributing to significant morbidity, mortality, and healthcare burdens worldwide. Epidemiologically, resistance hotspots have emerged in Asia, Europe, and the Middle East, while hvKP continues to expand beyond its original endemic regions. Diagnostic challenges, therapeutic limitations, and economic pressures further complicate clinical management. This review synthesizes current knowledge on K. pneumoniae virulence mechanisms, resistance evolution, epidemiology, and clinical impact, and highlights emerging therapeutic strategies aimed at overcoming this escalating public health threat.