Effective Phages as Green Antimicrobial Agents Against Antibiotic-Resistant Hospital Escherichia coli

Abstract

Background: Bacteriophages are viruses that attack bacteria and lead to their lysis in an efficient and highly specific manner. These natural enemies of bacteria were used as therapeutic agents before the advent of antibiotics. Currently, with the rapid spread of multidrug resistant bacteria, phage therapy can be an effective alternative treatment for antibiotic resistant bacteria. Objectives: This study evaluated the effectiveness of bacteriophages in removing antibiotic-resistant clinical Escherichia coli strains in vitro and in vivo. Patients and Methods: Different samples were taken from bed sore and foot ulcers of patients with diabetes. Escherichia coli strains were isolated and identified by standard methods. The antibiogram was ascertained using the Kirby Bauer disc diffusion method for ten antibiotics. The bacteriophages were isolated from environmental water samples. They were exposed to the host bacteria by the double-layer agar technique (DLA) to observe plaques. Cross reaction of the phages on test Escherichia coli strains was performed to determine broader-spectrum phages. Phage TPR7 was selected for animal trials. Five groups of mice including a control group, bacterial group, phage group, antibiotic therapy group and phage therapy group, were examined. Results: Ten Escherichia coli strains were isolated from hospital samples. They showed high resistance to the used antibiotics. An effective bacteriophage was isolated for each strain. The cross-reaction showed phages which affect more than six Escherichia coli strains. They can be a good choice for clinical therapeutic use. In animal trials the group challenged with phages after being infected showed similar results as the group treated with gentamicin after being infected. In both groups infection was removed after 48 hours. Conclusions: According to the results, six strains were resistant to six or seven antibiotics and all strains were at least resistant to two antibiotics. However, for each of these resistant bacteria one bacteriophage was isolated from environmental samples, which showed the effectiveness of bacteriophages to remove clinically resistant Escherichia coli strains. Effective phages in vitro showed effective results in vivo as well.