Evaluation of bacteriophage cocktail on septicaemia caused by colistin-resistant Acinetobacter baumannii in immunocompromised mice model

Abstract

Background & objectives: Since the bacterium, Acinetobacter baumannii (AB) has acquired resistance to almost all commercially available antibiotics, the search for alternative treatment options continues to be need of the hour. Bacteriophage therapy seems to be the most promising amongst various proposed alternatives (e.g. antimicrobial peptides, bacteriocin, probiotics, etc.). The present study, therefore, aimed to evaluate the effect of different dosages of specific phages in immunocompromised rodents in a septicaemia model caused by AB mimicking real clinical situations.

Methods: The three most active and unique phages (ɸAb4, ɸAb7 and ɸAb14) were selected for this study. A constant dose (100 μl of 10⁸ pfu/ml) of AB was given in all the experiments. Five different sets of experiments were designed: prophylactic administration of phage cocktail in the volume of 100 μl (10⁹ pfu/ml) before and simultaneous with the bacterial challenge; and therapeutic i.e. administration of phage cocktail six, 12 and 24 h after bacterial challenge. Since there were deaths in mice when phage was given 24 h after bacterial challenge, the reduced dosage i.e. 100 μl of 10⁷, 10^[6], 10⁵ pfu/ml of phage cocktail was also evaluated.

Results: The administration of 100 μl (10⁹ pfu/ml) of phage cocktail after six, 12 and 24 h of the bacterial challenge resulted in the mortality ranging between 20 to 60 per cent. However, no mortality could be observed with simultaneous or prophylactic administration of phages with the bacterial challenge. No mortality was observed with reduced doses of the cocktail (10^[6] and10^[5] pfu/ml).

Interpretation & conclusions: As per the results of this study, it may be concluded that even if patients with acute infections report late to the hospital, a relatively low dose of the phage cocktail may be therapeutically beneficial.

Keywords: Acinetobacter baumannii; bacteriophage cocktail; colistin-resistant; endotoxins; multidrug resistant; phage therapy; septicaemia.

Figure

The outcome of the phage therapy on Acinetobacter baumannii septicaemia at different time points and dosage. Details of study groups: A1- bacterial challenge and phage cocktail given simultaneously, A2-phage cocktail given six hours before bacterial challenge, A3 phage cocktail given six hours after bacterial challenge, A4-phage cocktail given 12 h after bacterial challenge; A5-phage cocktail given 24 h after bacterial challenge with 1x10⁸ cfu/ml, A5.1, A5.2 and A5.3 all with bacterial challenge dose 10⁸ cfu/ml and phage cocktail administered consisted of 10⁷, 10⁶, and 10⁵ cfu/ml.