Oral Presentation Lorne Infection and Immunity 2022

Phage-antibiotic combination is a superior treatment against multi-drug resistant Acinetobacter baumannii (#39)

Jeremy Barr 1
  1. Monash University, Clayton, VIC, Australia

Phage therapy is becoming increasingly promising as a therapeutic strategy against antibiotic-resistant bacterial infections. Importantly, clinical phage therapy is often delivered alongside antibiotics. Therefore, to maximise their therapeutic effect, the biology of clinically-relevant phages needs to be better understood. Here, we assessed the in vivo bactericidal effect of a phage-antibiotic combination on Acinetobacter baumannii AB900 using phage FG02, which binds to capsular polysaccharides and leads to antimicrobial resensitisation in vitro. We performed a two-stage preclinical trial using a murine model of severe bacteraemia. Notably, our findings explain the mechanism through which the combination of these two agents results in a superior bactericidal effect. We confirm that, even in complex in vivo systems, treatment with a capsule-targeting phage can reliably and repeatably induce bacterial evolution towards a phenotype that is phage-resistant but resensitised to antibiotics. This study presents a preclinical trial, the first using a mammalian model, that demonstrates that a phage antibiotic combination has a superior bactericidal effect than each of these agents individually against severe A. baumannii infection.