Phage therapy against Klebsiella pneumoniae infections: integrating host-phage immune interactions, therapeutic strategies, and clinical translation.

The emergence of convergent multidrug-resistant (MDR) and hypervirulent (hvKp) lineages has transformed Klebsiella pneumoniae into a major global health threat. Frequently associated with hospital-acquired pneumonia, bacteremia, urinary tract infections (UTIs), meningitis, and sepsis, these strains disproportionately affect elderly, immunocompromised, and critically ill patients, resulting in high morbidity and mortality. Their rapid dissemination has further intensified the global antimicrobial resistance (AMR) crisis, highlighting the urgent need for therapeutic strategies beyond conventional antibiotics. Although bacteriophages have demonstrated considerable potential as antibacterial agents, their successful clinical application depends on factors extending beyond bacterial eradication alone. This review critically integrates current evidence on therapeutic efficacy, host-phage immune interactions, delivery optimization, phage-antibiotic synergy, phage-derived therapeutics, AI-assisted phage discovery, and translational considerations within a unified framework for K. pneumoniae infections. It further examines how these interconnected determinants collectively influence therapeutic outcomes and discusses emerging strategies for precision phage therapy. By adopting this integrated translational perspective, the review identifies the key factors governing successful clinical implementation and provides a framework for advancing bacteriophage therapy against multidrug-resistant K. pneumoniae infections.