Phage-meropenem synergy against OXA-48-producing Klebsiella pneumoniae clinical isolates

Abstract

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 phages to target bacterial pathogens, is a promising approach, particularly when combined with antibiotics to enhance efficacy through synergistic interactions. In this study, time-kill curve assays were used to evaluate the synergy between the lytic phage vB_Kpn_2-P4 and meropenem against twelve K. pneumoniae clinical isolates from Spanish hospitals that carried diverse carbapenemases. Notably, in OXA-48-producing isolates, this combination prevented the emergence of resistant mutants, highlighting the therapeutic potential of phage-antibiotic synergy. The observed effect, linked to the presence of the pOXA-48 plasmid, suggests a promising strategy for combating multidrug-resistant bacteria.