Safety and Efficacy Assessment of Bacteriophages Isolated from Kibera, Kenya Wastewater Plant, against Multidrug-Resistant<i> Pseudomonas aeruginosa</i> Infection in BALB/c Mice

Abstract

Pseudomonas aeruginosa is a pathogen of great clinical importance to both humans and animals. It causes pneumonia in cystic fibrosis patients, and it is responsible for the infections of blood and lungs during surgery. Increased antibiotic use has led to the emergence of multidrug-resistant strains of P. aeruginosa. Recently, phage therapy has attracted much attention as a promising alternative against the increasing antimicrobial resistance. This study determined the safety and efficacy of phage therapy against virulent P. aeruginosa in a murine model. Phage PaCIKb2 was isolated from sewage water. Morphological characterization by transmission electron microscope was done. We assessed the phages' antimicrobial effect in vitro and in biofilms, its growth kinetics, host ranges, temperature and pH stability. Therapeutic safety and efficacy were observed 24 hours post-infection with virulent P. aeruginosa in a murine model. Transmission Electron Microscopy revealed phage PaCIKb2 to belong to the family myoviridae. The phage was found to be high temperature tolerant (up to 50°C). It was active between pH ranges (5 and 11), had a latent period of 15 minutes with a burst size of 316 viral particles, and exhibited a narrow host range. After intravenous phage administration dose (2×109 PFU/ml) post-infection with virulent P. aeruginosa, the presence of phages in vivo and reduction of bacterial loads in mice was observed. A reduction in mice tissue inflammation suggested the effectiveness of phage PaCIKb2 phage therapy. This research gives data that supports the use of phage therapy against multidrug-resistant P. aeruginosa.