In vitro activity of cefiderocol against Gram-negative aerobic bacilli in planktonic and biofilm form–alone and in combination with bacteriophages

Multi-drug resistant Gram-negative pathogens are increasingly difficult-to-treat perpetrators of infections. New, innovative, and more multifaceted therapies for the treatment of multi-drug resistant strains are thus urgent to hinder further drug resistance and mitigate deadly, untreatable infections. Our study aimed to investigate the efficacy of cefiderocol against Gram-negative aerobic bacteria alone and in combination with phages. The minimum inhibitory concentration (MIC) of cefiderocol was determined using the microdilution broth method, while the minimum biofilm bactericidal concentration was assessed using isothermal microcalorimetry. The combined effect of cefiderocol and phages was evaluated using colony-forming unit counts. Results demonstrated a notable antibacterial effect of cefiderocol, with 83.4% of tested strains exhibiting susceptibility. When combined with phages, the MIC of cefiderocol was reduced by 2-64-fold, indicating a synergistic interaction between the two agents. Furthermore, the combination therapy showed enhanced efficacy against biofilm compared to monotherapy with either cefiderocol or phages alone, leading to complete biofilm elimination in certain cases. This study highlights the potential of combining cefiderocol with phages as a strategy to combat multi-drug resistant Gram-negative bacterial infections. The observed synergy suggests that this combination therapy could improve treatment outcomes and help address the challenges of antibiotic resistance and biofilm-associated infections.