Therapeutic Effectiveness Of Bacteriophages In The Rescue Of Mice With Extended-spectrum β-lactamases-producing Escherichia Coli Bacteremia

Objective To study the treatment efficacy of phage with broad host range isolated from hospital sewage against infection caused by extended-spectrumβ-lactamases (ESBLs)-producing Escherichia coli in mice.Methods To isolate the specific phages against ESBL-producing E. coli from hospital sewage and then to select the phage with broad host range in vitro. 30 ESBL-producing E.coli strains were used to isolate specific phages from hospital sewage and then the phage with broad host range was screened. The phage was identified by adsorption rate, one step growth experiment and negative staining for transmission electron microscope (TEM).The broad host range phage was used to rescue mice from bacteremia caused by clinical isolations of ESBL-producing E. coli.Results The broad-host-range phage ?9882 was screened out and it could cause 36.7% bacteriolysis among all those 30 ESBL-producing E. coli strains. About 98% of phage was adsorbed to host bacteria within 5 minitues. The latent period is about 30~40 min and the burst size is about 110. The ultrastructure analysis under electron microscope demonstrated that the phage ?9882 has a roundshaped head with diameter 70nm, and a short tail of 100nm in length. Purified phage ?9882 can rescue 100% of the bacteremic mice at the MOI (multiple of infection)≥10-4. About 60% of mice survived even when the treatment is delayed for 1h by using ?9882 (MOI, 200). Treatment of bacteremic mice with the heat-inactivated phage resulted in a 0% survival rate.Conclusion The phage ?9882 screened had relatively a broad host range, a high adsorption rate and a short latent period. The investigation of the its characteristics will provide the first experimental evidence to validate the clinical application of phage therapey. Our study provides the experimental evidence that the broad host range phage ?9882 shows significant treatment efficacy against experimental ESBL-producing E. coli infection in mice without any adverse effects, thereby implying clinical applicability of phage to control clinical ESBL-producing E. coli-induced infection diseases.