Sequential treatment effects on phage-antibiotic synergistic application against multi-drug-resistant Acinetobacter baumannii

Bacteriophage (phage) therapy, exploiting phages which are the natural enemies of bacteria, has been reintroduced to treat multidrug-resistant (MDR) bacterial infections. However, some intrinsic drawbacks of phages are overshadowing their clinical use, particularly the narrow host spectrum and rapid emergence of resistance upon treatment. The use of phage-antibiotic combinations exhibiting synergistic bacterial killing [termed 'phage-antibiotic synergy' (PAS)] has therefore been proposed. It is well reported that the types and doses of phages and antibiotics are critical in achieving PAS. However, the impact of treatment order has received less research attention. As such, this study used an Acinetobacter baumannii phage vB_AbaM-IME-AB2 and colistin as a model PAS combination to elucidate the order effects in-vitro. While application of the phage 8 h before colistin treatment demonstrated the greatest antibacterial synergy, it failed to prevent the development of phage resistance. On the other hand, simultaneous application and antibiotic followed by phage application were able to suppress/delay the development of resistance effectively, and simultaneous application demonstrated superior antibacterial and antibiofilm activities. Further in-vivo investigation is required to confirm the impact of treatment order on PAS.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

Bacteriophage therapy, utilizing phages as natural enemies of bacteria, is being reintroduced to treat multidrug-resistant bacterial infections. However, the narrow host spectrum and rapid emergence of resistance limit their clinical use. Therefore, the combination of phages and antibiotics, known as phage-antibiotic synergy (PAS), is proposed. This study utilized an Acinetobacter baumannii phage and colistin as a model to investigate the impact of treatment order on PAS. The results showed that simultaneous application of phage and antibiotic effectively suppressed the development of resistance and demonstrated superior antibacterial and antibiofilm activities.