Supplementary Information for Optimized therapeutic option against Resistant Klebsiella Pneumoniae infection: revisiting phage therapy

Multi-drug resistant and carbapenem-resistant hypervirulent <i>Klebsiella pneumoniae</i> are spreading globally at an alarming rate, emerging as one of the most serious threats to global public health. The formidable challenges posed by the current arsenal of antimicrobials highlight the urgent need for novel strategies to combat <i>K. pneumoniae</i> infections. This review begins with a comprehensive analysis of the global dissemination of virulence factors and critical resistance profiles in <i>K. pneumoniae</i>, followed by an evaluation of the accessibility of novel therapeutic approaches for treating <i>K. pneumoniae</i> in clinical settings. Among these, phage therapy stands out for its considerable potential in addressing life-threatening <i>K. pneumoniae</i> infections. We critically examine the existing preclinical and clinical evidence supporting phage therapy, identifying key limitations that impede its broader clinical adoption. Additionally, we rigorously explore the role of genetic engineering in expanding the host range of <i>K. pneumoniae</i> phages, and discuss the future trajectory of this technology. In light of the 'Bad Bugs, No Drugs' era, we advocate leveraging artificial intelligence and deep learning to optimize and expand the application of phage therapy, representing a crucial advancement in the fight against the escalating threat of <i>K. pneumoniae</i> infections.