N KARUMIDZE¹, O.J. BERNASCONI¹, D JGENTI², M GODERDZISHVILI², A ENDIMIANI<sup>1

1</sup>Institute for Infectious Diseases, University of Bern, Bern, Switzerland, ²Eliava Institute of Bacteriophages, Microbiology and Virology, Tbilisi, Georgia

Background: Infections due to MDR E. coli represent a public health concern. These pathogens are resistant to the last-generation cephalosporins due to the production of extended-spectrum β-lactamases (ESBLs) and/or plasmid-mediated AmpCs (pAmpCs), leaving carbapenems as last options. However, also these drugs can be hydrolyzed by carbapenemases. One of the alternative ways to treat infections caused by these MDR pathogens could be the use of bacteriophages.

Methods: The spot test susceptibility method was used to evaluate two commercially available bacteriophage cocktails (Pyophage and Intestiphage; EliavaBiopreparations, Tbilisi, Georgia) and the vB_GEC_E. coli_AI monophage (George Eliava Collection) against 60 previously characterized non-clonal E. coli strains isolated from humans and animals. The collection included ESBL (n=26; of which 16 CTX-M-15-like), pAmpC (n=15; of which 12 CMY-2-like), carbapenemase producers (n=7; of which 5 NDM) and controls. Strains were grown in 5ml BHI broth for 4 hrs at 37°C. Then, they were transferred on BHI agar plates to form lanes. Ten µl of phages were subsequently spotted on each bacterial lane. Plates were incubated for 18 hrs. Results were defined as “resistant” when no phage(s) activity was observed.

Results: Overall, susceptibility to Pyophage, Intestiphage, and monophage was 85%, 82% and 66%, respectively. In particular, 96%, 92% and 81% of ESBL producers were susceptible to Pyophage, Intestiphage and monophage, respectively. With regard to pAmpC producers, 86.6% were susceptible to either Pyophage or Intestiphage, whereas 54% were susceptible to the monophage. Overall, only 8% of the strains (of which 2/7 carbapenemase producers) tested resistant to all three phage compounds. We did not recorded differences between the strains collected from humans and animals.

Conclusion: Our data indicates that bacteriophages may be considered as a possible option to treat infections due to MDR E. coli, including those pan-drug resistant due to production of carbapenemases. However, strains should undergo appropriate phage susceptibility tests before implementation.

This work was supported by SNF grant No. 153377 to AE