Project name: Identification and Evaluation of a Phage Cocktail with High Lytic Activity Against Escherichia coli including Extended-Spectrum Beta-Lactamase (ESBL)- Producing Isolates - A Preclinical Study

Description: Antimicrobial resistance rates have dramatically increased among hospitalized patients worldwide and infections caused by these organisms are often associated with prolonged treatment courses and adverse outcomes. The World Health Organization recently classified Escherichia coli (EC) as pathogen of international concern as antibiotic-resistant strains are on the rise and may cause severe infections, especially in immunocompromised patients. New therapeutic options are thus urgently needed and the use of EC specific bacteriophages (in short: phages) might be a promising approach. Antibiotic resistant bacteria do not implicate resistance to phages, thus EC phages also target resistant isolates such as extended-spectrum beta-lactamase (ESBL) producers. We therefore want to conduct a preclinical study including two work packages (WPs). First, we aim to identify single phages with high lytic activity against EC isolates. For getting a broad bacterial phage coverage, we will test a large number of diverse EC isolates, including ESBL-producers collected within previous studies against a high number of genetically and morphologically diverse phages. The phages with the highest lytic activity will be selected and combined in a synergistic phage mixture (cocktail) (WP1). In the second part of the project, we intend to evaluate the bacterial coverage of this newly designed phage cocktail. EC isolates for this analysis will be collected prospectively from hematological and oncological high-risk patients (WP2). The study will provide novel insights into the characteristics and lytic effects of phages targeting EC allowing for broad applicability of the results as bacterial isolates collected from different regions of the world will serve as hosts for phage selection. Moreover, results of the study will serve as baseline for preparation of consecutive translational trials evaluating the impact of EC phage cocktails on the human microbiota and its applicability for therapeutic use, especially in hematological/oncological high-risk patients.

Data type: Other

Sample scope: Monoisolate

Last updated: 2022-06-02