Therapeutic potential of novel phages with antibiotic combinations against ESBL-producing and carbapenem-resistant Escherichia Coli

Objectives

The emergence of extended-spectrum β-lactamase (ESBL)-producing E. coli and carbapenem-resistant E. coli (CREC) is a significant global health challenge. This study focuses on isolating and characterizing two novel phages, EC.W1–9 and EC.W15–4, and investigating their efficacy with antibiotics against these resistant E. coli.

Methods

In vivo experiments were conducted using BALB/c mice, and E.coli isolates were collected, cultured, and evaluated for antibiotic susceptibility. Phages were isolated from hospital sewage and prepared to infect the E. coli.

Results

The isolated phages, EC.W1–9 and EC.W15–4, belonged to the Podoviridae and Straboviridae families, and lack integrase or toxin-coding genes, indicating safety for therapeutic use. The combination of these phages significently enhanced their lytic ability, lysing 61.7% of 60 E. coli isolates, compared to 41.6%–55% lysis by individual phages. Furthermore, the phage combination demonstrated 100% susceptibility against different E. coli sequence types, including ST73, ST648, ST2311, ST405, ST7962, ST131, ST13003, and ST167. Additionally, synergy between antibiotics and phage combinations improved susceptibility rates to 73.3% for ESBL producers and 54% for CREC. The combined treatment of isolated phages and antibiotics significantly increased survival rates in BALB/c mice exposed to resistant STs of E.coli, including ST131, ST648, and ST410. Survival rates against ST131 increased by approximately 75% and 50% compared to treatment individual phages. Combined treatment with two phages and antibiotics resulted in 75–100% survival against E. coli ST410 and 100% survival against ST648

Conclusions

This study highlights the therapeutic importance of phage and phage-antibiotic combinations in combating ESBL-producing E. coli and CREC isolates.