Antibacterial effect of phage cocktails and phage-antibiotic synergy against pathogenic <i>Klebsiella pneumoniae</i>

Abstract

The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) <i>K. pneumoniae</i> strains in <i>in vitro</i> and <i>in vivo</i> context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse <i>K. pneumoniae</i> pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.