Phage-antibiotic combination: a possible approach to combatting a clinical carbapenem-resistant Pseudomonas aeruginosa

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a critical public health threat due to its extensive antimicrobial resistance and biofilm-forming ability, which limits the efficacy of conventional antibiotic therapies. Bacteriophage (phage) therapy offers a promising alternative. Methods The antibacterial and antibiofilm activities of the lytic phage MYY9 against the clinical CRPA isolate CRPA-11d were evaluated. The effects of MYY9 alone and in combination with meropenem were assessed using bacterial killing assays, biofilm biomass quantification, extracellular polymeric substance (EPS) analysis, and membrane integrity assays based on N-phenyl-1-naphthylamine (NPN) uptake. The therapeutic efficacy of MYY9-meropenem combination therapy was further investigated in a murine model of acute CRPA pneumonia by evaluating pulmonary bacterial loads, inflammatory responses, clinical severity, and histopathological changes. Results MYY9 treatment was associated with reduced EPS-associated polysaccharide signals, increased reducing-sugar levels in isolated EPS preparations, and decreased established biofilm biomass. Increased NPN uptake was also observed following MYY9 treatment. In time-kill assays, culture-based enumeration showed fewer recoverable colonies in the MYY9-containing groups, followed by a subsequent increase during incubation, whereas the MYY9-meropenem combination maintained lower bacterial counts throughout the observation period. In the murine pneumonia model, the combination group showed lower recoverable bacterial counts from lung homogenates, reduced pro-inflammatory cytokine production, alleviated clinical symptoms, and improved pulmonary histopathological outcomes compared with untreated controls and either monotherapy. Conclusion MYY9 showed antibacterial and antibiofilm activity against CRPA-11d, while the MYY9-meropenem combination was associated with greater antibacterial activity and improved short-term outcomes in the murine pneumonia model. These findings provide preliminary evidence for the activity of this combination against CRPA-11d and support further investigation across additional isolates and more comprehensive experimental settings.