Efficacy of Newly Isolated and Highly Potent Bacteriophages in a Mouse Model of XDRAB Bacteremia.

Abstract Objectives Bacteremia can be caused by Acinetobacter baumannii with clinical manifestations ranging from transient bacteremia to septic shock. Extensively drug-resistant A. baumannii (XDRAB) strains producing the New Delhi metallo-s-lactamase, which confers resistance to all s-lactams including carbapenems, have emerged and infected patients suffer increased mortality, morbidity and length of hospitalization. The lack of new antimicrobials led to a renewed interest into phage therapy, the so-called forgotten cure. Accordingly, we tested new lytic bacteriophages in a Galleria mellonella and a mouse model of XDRAB-induced bacteremia. Methods Galleria mellonella were challenged with 5.10 5 CFU of the XDRAB strain FER. Phages vB_AbaM_3054 and vB_AbaM_3090 were administrated alone or in combination 30 min. after bacterial challenge. Saline and imipenem were injected as controls. Mice were challenged i.p. with 6.10 7 CFU of A. baumannii FER. vB_AbaM_3054 and vB_AbaM_3090 were administrated i.p. alone or in combination 2 h 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. Results Phage-based treatments showed high efficacy in larvae (ca. 100% survival at 80 h) and mice (ca. 100% survival at day 7) compared to the untreated control (0% survival at 48 h and 24 h in larvae and mice, respectively). Conclusions The present data reporting efficacy of phage therapy in a mouse model of bacteremia support the development of phage-based drugs to manage infection due to multi-drug resistant A. baumannii and particularly XDRAB.