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

Lead Research Organisation: Liverpool School of Tropical Medicine
Department Name: Tropical Disease Biology

Abstract

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.

Technical Summary

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.

Publications

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Title Project logo 
Description Artists, Natasha Niethamer and artist with MA Art in Science by the Liverpool School of Art & Design at Liverpool John Moores University developed a log by a collaborative process within STRESST consortium. Please find the logo in STRESST website - https://www.lstmed.ac.uk/stresst 
Type Of Art Artwork 
Year Produced 2022 
Impact The logo has been used for the awareness of the project via Twitter STRESST account and in the official STRESST website in the Liverpool School of Tropical Medicine. 
URL https://www.lstmed.ac.uk/stresst
 
Description Chemical analysis of environmental samples - ADAM TO CHECK 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Adam to complete
Collaborator Contribution Adam to complete
Impact Adam to complete
Start Year 2022
 
Description Presentation of STRESST work at EMBO workshop "Plasmids as vehicles of AMR spread" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact One of the PIs of the STRESST consortium, Dr. Adam Roberts, was invited to present the work that STRESST is doing, particularly focusing on the latest paper published:

Title: Development of pBACpAK entrapment vector derivatives to detect intracellular transfer of mobile genetic elements within chloramphenicol-resistant bacterial isolates.
Journal: Journal of Microbiological Methods, Volume 213, 2023.

Dr. Roberts shared insights into the research during the presentation.
Year(s) Of Engagement Activity 2023
URL https://meetings.embo.org/event/23-amr-plasmids
 
Description STRESST project presentation in BDRI Strategic retreat 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact 30 researchers and staff from the Liverpool School of Tropical Medicine and Malawi-Liverpool-Wellcome Programme staff attended to the Bacterial and Drug Resistant Infections Strategic retreat where former and new research projects were discussed. Dr Sabrina Moyo - Researcher at Haukeland University Hospital, Norway and an Honorary Research associate in LSTM - introduced to the teams STRESST project.
Year(s) Of Engagement Activity 2022
 
Description STRESST project presentation in the seminar "Antimicrobial resistance surveillance in environmental and human samples" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This seminar, which took place at Haukeland University Hospital, aimed to gather international speakers to discuss the problem of antimicrobial resistance from various perspectives, including its implications in a One Health context. The organizer of the seminar invited Dr. Adam P. Roberts to present the work of the STRESST project.
Year(s) Of Engagement Activity 2023
URL https://camria.w.uib.no/2023/08/29/event-on-antimicrobial-resistance-surveillance-in-environmental-a...
 
Description Speaker in a webinar 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The webinar was a collaborative effort by several prominent international organizations specializing in the area of Antimicrobial Resistance (AMR). The Principal Investigator (PI) of the STRESST project was invited as one of the speakers for this event. Each speaker, including the STRESST PI, was allocated a dedicated time of 30 minutes to present their insights, experiences, and findings. The webinar focused on the One Health AMR Genomics for WGS Integration to AMR Surveillance
, offering a comprehensive exploration of the pressing issues, innovative approaches, and collaborative strategies to address these multifaceted challenges.

This interactive session was not merely a series of lectures; it also incorporated an open discussion segment after the talks, allowing participants to engage in conversations, share perspectives, and exchange ideas. By showcasing the STRESST project within the context of AMR and One Health, the PI provided a deeper understanding of how the initiative contributes to this crucial domain. Attendees were eligible to receive a certificate of attendance after furnishing their requisite details.
Year(s) Of Engagement Activity 2023
URL https://tinyurl.com/mr3mekz9
 
Description Workshop on Plasmids as Vehicles of Antimicrobial Resistance Spread - The Abdus Salam International Centre for Theorical Physics/Imperial College London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Adam
Year(s) Of Engagement Activity 2022
URL https://indico.ictp.it/event/9875/material/4/3.pdf