Phage and antibiotic combination therapy reduces bacterial growth of multidrug resistant CF derived P. aeruginosa

<bold>Aim:</bold> To investigate the potential of phage therapy combined with antibiotics in suppressing bacterial growth of multidrug resistant P. aeruginosa isolated from individuals with cystic fibrosis (CF). <bold>Background:</bold> <italic>P. aeruginosa</italic>, a common pathogen colonising the lungs of individuals with CF becomes difficult to treat and contributes to increased morbidity and mortality in this population. With a lack in new antimicrobials, alternative treatment options including bacteriophage (phage) therapy is now critical. <bold>Methods:</bold> Overnight cultures of nine tobramycin-resistant <italic>P. aeruginosa</italic> clinical isolates, were adjusted to 10⁵ CFU/mL and 100 µL added to each well of a 96-well culture plate. <italic>P. aeruginosa</italic> was then treated with 100 µL of tobramycin (4 µg/mL) or phage (KM3, BM12, MM1; MOI 10, 10⁶ PFU/mL) singularly or in combination to assess treatment efficacy. Bacterial suspensions were incubated for 24 h and overall bacterial growth (OD600_nm) measured. Fractional inhibition concentration index (FICi) was calculated to assess for synergism. <bold>Results:</bold> <italic>P. aeruginosa</italic> treated with 4 µg/mL of tobramycin (4-16-fold lower than the MIC) and phages resulted in the reduction of overall bacterial growth (KM3: 46.9-88.8%; BM12: 22.8-86.1%; MM1: 17.9-83.5%). The FICi of tobramycin and phages (KM3, BM12 or MM1) were between 0.0-1.9 demonstrating synergistic (≤0.5) or no interaction (0.5-4) activities depending on the clinical isolate. No antagonistic interaction was observed. <bold>Conclusions:</bold> This study demonstrates the potential of combination treatments, including the delay of resistance development. Furthermore, lower concentrations of antibiotics used may have a positive impact on future stewardship.