Efficacy of newly isolated and highly potent bacteriophages in a mouse model of extensively drug-resistant Acinetobacter baumannii bacteraemia.

Bacteraemia can be caused by Acinetobacter baumannii (A. baumannii), with clinical manifestations ranging from transient bacteraemia to septic shock. Extensively drug-resistant A. baumannii (XDRAB) strains producing the New Delhi metallo-ß-lactamase, which confers resistance to all ß-lactams including carbapenems, have emerged. Infected patients suffer increased mortality, morbidity and length of hospitalisation. The lack of new antimicrobials has led to a renewed interest in phage therapy, the so-called forgotten cure. Accordingly, we tested new lytic bacteriophages in a Galleria mellonella and a mouse model of XDRAB-induced bacteraemia. Galleria mellonella were challenged with 5.10 <sup>5</sup> CFU of the XDRAB strain FER. Phages vB_AbaM_3054 and vB_AbaM_3090 were administrated alone or in combination 30min after bacterial challenge. Saline and imipenem were injected as controls. Mice were intraperitoneally (i.p.) challenged with 6.10 <sup>7</sup> CFU of A. baumannii FER. vB_AbaM_3054 and vB_AbaM_3090 were administrated i.p. alone or in combination 2h after bacterial challenge. Saline and imipenem were injected as controls. Larvae and mice survival were followed for 7 days and compared with Log-Rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests. Phage-based treatments showed high efficacy in larvae (ca. 100% survival at 80h) and mice (ca. 100% survival at day 7) compared with the untreated controls (0% survival at 48h and 24h in larvae and mice, respectively). The present data reporting efficacy of phage therapy in a mouse model of bacteraemia support the development of phage-based drugs to manage infection due to multi-drug resistant A. baumannii and particularly XDRAB