Phage therapy

Antimicrobial resistance is a growing global healthcare crisis, driven by the rapid spread of resistant pathogens that compromise existing treatments. Carbapenem-resistant Klebsiella pneumoniae is a major public health threat, requiring novel therapeutic strategies. Phage therapy, which employs bacterial viruses, is a promising approach, particularly when combined with antibiotics to enhance efficacy through synergistic interactions. In this study, we evaluated the synergy between the lytic phage vB_Kpn_2-P4 and meropenem against twelve K. pneumoniae clinical isolates circulating in Spanish hospitals carrying diverse carbapenemases. Interestingly, in OXA-48-producing isolates, phage vB_Kpn_2-P4 in combination with meropenem delayed or prevented the emergence of resistance, highlighting the therapeutic potential of phage-antibiotic synergy. This observation was validated by genome-wide association analysis, confirming the link to the presence of the pOXA-48 plasmid in the bacterial isolates, suggesting a promising strategy for combating multidrug-resistant bacteria.