April 21, 2020  |  

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

Authors: Leshkasheli, Lika and Kutateladze, Mzia and Balarjishvili, Nana and Bolkvadze, Darejan and Save, Jonathan and Oechslin, Frank and Que, Yok-Ai and Resch, Grégory

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-ß-lactamase, which confers resistance to all ß-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.Galleria mellonella were challenged with 5.105 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 6.107 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.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).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.Copyright © 2019. Published by Elsevier Ltd.

Journal: Journal of global antimicrobial resistance
DOI: 10.1016/j.jgar.2019.05.005
Year: 2019

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