Combatting multidrug resistance in Klebsiella pneumoniae: mechanisms, global trends, and innovative therapeutic strategies.

Emergence of drug-resistant bacterial infections, particularly those caused by Klebsiella pneumoniae, represents a growing public health issue. K. pneumoniae is the leading cause of nosocomial infections, associated with diverse diseases and high mortality rates. Its ability to develop multiple resistance mechanisms, including biofilm formation, efflux pump activity, β-lactamase production, enzymatic modification, and porin loss, contributes to its resistance to conventional antibiotics. These challenges urge the ned for novel therapeutics and alternative therapies. While resistance rates remain lower in developed countries, regions in Africa, South Asia, and Middle East report rates exceeding 80%, often due to antibiotic misuse and inadequate regulations. Particularly concerning are novel hypervirulent carbapenem-resistant strains linked to bloodstream infections and high mortality, especially in low- and middle-income countries. Emerging approaches, including fecal microbiota transplantation, might help gut dysbiosis and enhance host immunity against carbapenemase-producing Enterobacterales. Additionally, molecular studies identified cytoplasmic response regulators that promote resistance gene expression and plasmid-mediated transfer, offering prospective therapeutic targets. This review summarizes current knowledge regarding the genetic, molecular, and epidemiological mechanisms of multidrug resistance and virulence in K. pneumoniae, and discusses emerging therapeutic strategies including new β-lactamase inhibitors, bacteriophage and host-directed therapies, in silico therapeutic strategies, and vaccine development.