AUTHOR=Singh Aprajita , Singh Alakh Narayan , Rathor Nisha , Chaudhry Rama , Singh Sudhir Kumar , Nath Gopal 

TITLE=Evaluation of Bacteriophage Cocktail on Septicemia Caused by Colistin-Resistant Klebsiella pneumoniae in Mice Model

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.778676

DOI=10.3389/fphar.2022.778676

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> The emergence of resistance against last-resort antibiotics, carbapenem and colistin, in <italic>Klebsiella pneumoniae</italic> has been reported across the globe. Bacteriophage therapy seems to be one of the most promising alternatives. This study aimed to optimize the quantity and frequency of bacteriophage cocktail dosage/s required to eradicate the <italic>Klebsiella pneumoniae</italic> bacteria in immunocompetent septicemic mice.</p><p><bold>Methods:</bold> The three most active phages ɸKpBHU4, ɸKpBHU7, and ɸKpBHU14 characterized by molecular and TEM analyses were in the form of cocktail and was given intraperitoneally to mice after inducing the septicemia mice model with a constant dose of 8 × 10<sup>7</sup> colony-forming unit/mouse (CFU/mouse) <italic>Klebsiella pneumoniae</italic>. After that, the efficacy of the phage cocktail was analyzed at different dosages, that is, in increasing, variable, constant, and repeated dosages. Furthermore, interleukin-6 and endotoxin levels were estimated with variable doses of phage cocktail.</p><p><bold>Results:</bold> We have elucidated that phage therapy is effective against the <italic>Klebsiella pneumoniae</italic> septicemia mice model and is a promising alternative to antibiotic treatments. Our work delineates that a single dose of phage cocktail with 1 × 10<sup>5</sup> plaque-forming unit/mouse (PFU/mouse) protects the mice from fatal outcomes at any stage of septicemia. However, a higher phage dosage of 1 × 10<sup>12</sup> PFU/mice is fatal when given at the early hours of septicemia, while this high dose is not fatal at the later stages of septicemia. Moreover, multiple repeated dosages are required to eradicate the bacteria from peripheral blood. In addition, the IL-6 levels in the 1 × 10<sup>5</sup> PFU/mouse group remain lower, but in the 1 × 10<sup>12</sup> PFU/mouse group remains high at all points, which were associated with fatal outcomes.</p><p><bold>Conclusion:</bold> Our study showed that the optimized relatively lower and multiple dosages of phage cocktails with the strict monitoring of vitals in clinical settings might cure septicemia caused by MDR bacteria with different severity of infection.</p>