Efficacy of Newly Isolated and Highly Potent Bacteriophages in a Mouse Model of XDRAB Bacteremia.
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BORIS DOI
Publisher DOI
PubMed ID
31100499
Description
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-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.
METHODS
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.
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.
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.
METHODS
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.
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.
Date of Publication
2019-12
Publication Type
Article
Subject(s)
Keyword(s)
A. baumannii MDRAB XDRAB bacteremia bacteriophage phage therapy sepsis
Language(s)
en
Contributor(s)
Leshkasheli, Lika | |
Kutateladze, Mzia | |
Balarjishvili, Nana | |
Bolkvadze, Darejan | |
Save, Jonathan | |
Oechslin, Frank | |
Resch, Grégory |
Additional Credits
Series
Journal of global antimicrobial resistance
Publisher
Elsevier
ISSN
2213-7165
Access(Rights)
open.access