Evaluating Synergy of Clinically Utilized Phage OMKO1 with Five Antibiotics from Different Classes against Pseudomonas aeruginosa

Abstract Decades of antibiotic overuse and misuse have placed us at the precipice of a post-antibiotic era. This rise in multidrug-resistant and pandrug-resistant bacteria poses a serious risk to public health, warranting urgent exploration of alternative treatment options for bacterial infections. One emerging method displaying promise in the field is phage-antibiotic combination therapy: the use of bacteriophages, viruses that exclusively infect bacteria, as adjuvants to antibiotics. This study investigated the synergistic effects of phage OMKO1, previously utilized in compassionate-use cases, with five antibiotics of diverse drug classes against Pseudomonas aeruginosa . Modified checkerboard assays were performed to test phage-antibiotic combination treatments across several antibiotic concentrations and phage multiplicities of infection. Synergy was achieved by four of the five phage-antibiotic pairings at sub-minimum inhibitory antibiotic concentrations. All combination treatments reduced the antibiotic minimum inhibitory concentration (MIC) by ≥ 2-fold and resulted in a reduction in resistant regrowth. These findings highlight the potential of phages to lower effective antibiotic concentrations and prolong their utility by slowing the rise of antimicrobial resistance.