Bacteriophage Indie resensitizes multidrug-resistant Acinetobacter baumannii to antibiotics in vitro

Antimicrobial resistance in Acinetobacter baumannii poses a significant global health challenge. Phage therapy, particularly through phage-antibiotic synergy (PAS), offers a promising strategy to combat this pathogen. This study demonstrated significant PAS, where the combination of phage Indie and ceftazidime achieved a bacterial reduction of more than 85% of A. baumannii strain AbAK03 at 17 h using low doses. Notably, this combination overcame phage resistance observed at 4 h when the phage was used alone, extending bacterial eradication by 13 h. Furthermore, phage Indie restored bacterial susceptibility to ceftazidime, supporting its role in improving interventional treatments against multidrug-resistant A. baumannii. To explore this interaction, phage Indie was isolated and characterized from multidrug-resistant clinical strains. An in vitro PAS experiment was performed using ceftazidime and piperacillin-tazobactam. The combination of phage Indie with ceftazidime consistently showed superior bactericidal effects compared to either agent alone, while the combination of phage Indie with piperacillin-tazobactam exhibited an antagonistic effect. These findings provide clear evidence supporting the application of phage-antibiotic combinations as an effective intervention strategy and lay the groundwork for future in vivo trials in a mouse model to combat antimicrobial resistance.