Antimicrobial Stewardship in Hospitals, Resistance Selection and Transfer in a One Health Context

The STRESST project (Antimicrobial Stewardship in Hospitals, Resistance Selection and Transfer in a One Health Context) will determine the effects of hospital-wide antimicrobial stewardship on the amount of antibiotics, and the numbers of susceptible and resistant bacteria, released in hospital wastewater. This data will show if stewardship can reduce the amounts of antibiotics and resistant bacteria entering the environment. Hospital wastewater is also likely to represent a hotspot for selection of antibiotic resistant bacteria. We will determine if the antibiotics present can catalyse both intracellular transposition and intercellular conjugation of mobile genetic elements carrying antibiotic resistance genes, and if this is less likely to occur following the antimicrobial stewardship intervention. In addition to agar plate-based assays, these experiments will also include state of the art animal caecum fermenter models which will directly link the healthcare environment (hospital) with the wider environment (via hospital wastewater) and animal health representing all three One Health areas. Ultimately, the STRESST project will demonstrate the effectiveness of antimicrobial stewardship in reducing antibiotic, and antibiotic resistant bacteria, release into the environment and how this impacts resistance transmission within and between microbial communities present in animals that use this as a water source. This holistic view of resistance transmission within a One Health context will serve to highlight a selection hotspot (hospital wastewater) for future interventions.

The " Antimicrobial Stewardship in Hospitals, Resistance Selection and Transfer in a One Health Context" (STRESST) project aims to determine the effects of hospital wide antimicrobial stewardship implementation on the levels of antibiotic residues and antimicrobial resistant bacteria leaving the hospital via wastewater. The point of collection of the wastewater will be on the perimeter of the hospital and will represent the boundary between the hospital environment and the wider environment. Once this data has been obtained it will be used to determine the effects on intracellular transposition and intercellular conjugation using state of the art molecular tools and fermenter systems which will enable us to model the chicken caecum.
The work will be carried out in five interlinked work packages as follows; 1) hospital wide antimicrobial stewardship implementation at the Queen Elizabeth Central Hospital in Malawi, 2) hospital wastewater sampling before and during antimicrobial stewardship implementation. This will be carried out using bespoke auto-samplers leading to retrieval of the microbiology and determination of concentrations of antibiotic residues. 3) Microbiological and genomic analysis of both susceptible and resistant bacteria to reveal the levels of different antibiotics and antibiotic resistance genes present within the sampled bacteria and 4) conjugation assays to determine the effects of antibiotic residues on intercellular transfer of AMR genes and finally 5) transposition assays to determine the effects of antibiotic residues on intracellular of AMR genes between replicons in the same cell.
At the end of the project we will be in a position to demonstrate the effects on AMR downstream of a hospital where robust antimicrobial stewardship interventions have been successfully implemented and highlight hospital wastewater as a site for future engineering solutions to completely remove antibiotic residues.