Hypervirulent and Drug-Resistant Klebsiella pneumoniae: Clinical Challenges and Alternative Treatment Strategies

Klebsiella pneumoniae is a major opportunistic pathogen responsible for a wide range of hospital- and community-acquired infections, including respiratory tract infections, urinary tract infections, meningitis, and liver abscesses. Among its emerging forms, hypervirulent K. pneumoniae (hvKp) has gained global attention due to its heightened virulence and ability to cause severe infections in healthy individuals. hvKp differs from classical K. pneumoniae (cKp) in its clinical presentation, often causing metastatic infections, liver abscesses without biliary disease, and multiple-site involvement. Despite initial antibiotic susceptibility, the recent convergence of hvKp virulence traits with antimicrobial resistance genes-especially those conferring multidrug resistance (MDR) and carbapenem resistance-poses a serious therapeutic challenge. This review highlights the epidemiological and clinical distinctions between hvKp and cKp, emphasizing the limitations of current diagnostic markers like the string test. Furthermore, it explores novel therapeutic strategies beyond conventional antibiotics, focusing on promising alternatives such as bacteriophage therapy and antimicrobial peptides (AMPs). Several phages, including PSKP16, vB_Kpn_F13, and phage cocktails, have demonstrated potent activity against hvKp strains, including biofilm-forming and carbapenem-resistant isolates. Likewise, AMPs such as Osmin, AA139-nanoformulations, and scorpion venom-derived Cm38 show efficacy in preclinical models. These emerging approaches hold potential to combat the rising threat of hvKp, especially strains that are extensively drug-resistant. Continued research and investment are essential to translate these findings into clinical practice and ensure effective management of hypervirulent and resistant K. pneumoniae infections.