Skip to main content
European Commission logo
English English
CORDIS - EU research results
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary

pREVention and management tools for rEducing antibiotic Resistance in high prevalence Settings

Periodic Reporting for period 1 - REVERSE (pREVention and management tools for rEducing antibiotic Resistance in high prevalence Settings)

Reporting period: 2021-07-01 to 2022-12-31

Resistance in bacteria can occur after exposure to antimicrobials either by selective pressure or by direct effects. In hospitals, the burden of resistance is further driven by gaps in infection prevention and control (IPC) or by sharing of resistance genes between bacteria. Infections caused by multidrug-resistant bacteria represent a serious challenge to healthcare in Europe due to limited options for treatment. Therefore, there is an urgent need to limit emerging antimicrobial resistance (AMR) and the spread of multidrug-resistant organisms (MDROs).

In hospitals, a number of strategies attempt to address AMR by reducing selection pressure or preventing healthcare-associated infections. Two such strategies are Infection Prevention and Control (IPC) programmes and Antibiotic Stewardship (ABS). In most studies, these strategies have been assessed independently; ignoring that transmission is related to multiple events rather than a single problem.

REVERSE seeks to address both AMR and healthcare-associated infections (HAI) in hospitals by building three programmes: Microbiology and Diagnostic Stewardship (MDS), Infection Prevention and Control (IPC), and Antimicrobial Stewardship (ABS). REVERSE will be able to tackle the complexity involved in transmission better than a single programme.

The primary objective of REVERSE is to develop cost-effective tools for the prevention and management of HAIs due of resistant bacteria and to reduce the number of these bacteria in areas where they are now common.

To accomplish this objective, REVERSE has a three-layered intervention:
The first layer is a randomized, clinical trial with 24 hospitals in four European countries (Greece, Italy, Romania, and Spain) promoting three interdependent prevention programmes (MDS, IPC, ABS). The next layer is an Implementation trial. Twelve out of the 24 REVERSE hospitals will receive comprehensive support from a team of implementation science experts to adapt the pre-built programmes to the context of the hospitals.

The final layer is a cost analysis consisting of two parts: a quality of life cohort study with micro-costing analysis, and a transferability experiment to low-and-middle-income countries (LMICs).

Patients with HAIs due to multi-resistant bacteria and patients without such infections will be compared by using quality-of-life questionnaires over a period of one year. Applying a micro-costing approach, differences between the patient groups can be translated into societal and economic costs. In a second step, healthcare workers from two LMIC will be asked to rank different elements of the REVERSE programme to estimate the level at which REVERSE can be transferred to their countries.
This is the first report for REVERSE. Much of the work during this reporting period has been to build the foundation for this complex trial. For brevity, tasks within a Work Package (WP) are summarised together with further details in the technical report.

WP1 is responsible for the management of the clinical trial in the 24 participating hospitals. During this reporting period, the hospitals were selected and contracts with the REVERSE National Focal Points were signed (Task 1.1). After a short delay due to the Omicron wave of the COVID-19 pandemic, the Kick-off meeting (Task 1.2) with all 24 hospitals was organized in early 2022 with data collection starting shortly after. The database is hosted and maintained by the University Hospital Zürich (Task 1.3). The first of the interventions (MDS) started in the first cohort of hospitals (Task 1.5) and lastly, planning for the Infection Control Implementation Workshops (delivered together with Work Packages 3 and 5) is in its final stages (Task 1.4).

WP2 is responsible for the MDS intervention, outbreak analysis, and repeated point prevalence surveys (PPS) of MDRO carriership. Work completed during this reporting period includes the assessment of the microbiology and diagnostic stewardship capacity of every hospital (Task 2.1) detailing of the outbreak definition, genetic investigation of the first reported outbreak (Task 2.2) and preparation for the first round of PPS swabs (Task 2.3).

WP3 is responsible for the IPC intervention. Work completed during this period includes a baseline survey assessing local IPC practices in the REVERSE hospitals, a review of national guidelines (Task 3.1) and the definition of the evidence based IPC bundles.

WP4 is responsible for the ABS intervention. During this period, a baseline survey was conducted to evaluate the ABS activities in the REVERSE hospitals (Task 4.1) and protocols were drafted for Tasks 4.2-4.6 (Basic and Advanced ABS interventions).

WP5 supports the Implementation of the IPC and ABS programmes in the REVERSE hospitals. Work completed includes a baseline survey to assess readiness for change in each hospital (with follow up video conferences) (Task 5.1) site visits to develop the tailored implementation strategy in the ENHANCED study sites (Tasks 5.2; site visits also involved WPs 1, 3, and 7), planning for training of local implementation teams (Task 5.3) and creation of an analysis plan for the summative evaluation (Task 5.5).

WP6 is responsible for the cost effectiveness layer of REVERSE. Work on Task 6.2 has started, with database setup, ethics approval, and patient recruitment for the nested quality of life cohort study.

WP7 includes the consortium and project management. During this reporting period, work continued on Tasks 7.1 and 7.2 including approval of an Amendment to the Grant Agreement. A plan for Data Management (Task 7.3) and Dissemination of Results (Task 7.4) was drafted and submitted to the commission and the Ethics deliverables due during this reporting period were also submitted (Task 7.5). An External Stakeholder Panel was assembled and the first meeting was organized in June 2022 (Task 7.6). In addition, visual identity was established with creating a website, social media accounts, and a newsletter.

WP8 is responsible for the ethics requirements. All deliverables due this reporting period were submitted as part of Task 7.5
We have laid the groundwork for a trial assessing both bundled prevention programmes on healthcare-associated infections due to MDRO as well as the adaptation of these programmes to local context within hospitals in high prevalence regions of antimicrobial resistance. These results will advance the knowledge base beyond the state of the art of single interventions, not only because of the anticipated results but also due to the applied multifaceted and multi-layered methodology. A study of this size and scope has not been done to test the effectiveness of combining MDS-, IPC- and ABS-programmes before, and no European study (to our knowledge) has assessed the impact of in-depth expertise of implementation science in adapting programmes to local contexts in this field.

The cost effectiveness framework resulting from REVERSE will be able to estimate effect and costs of the multifaceted REVERSE interventions on healthcare-associated infections due to MDRO and the impact of IPC and ABS on a societal level. This will allow visualisation of long-term costs of resistance on populations and potentially incentivise further research on prevention and therapy by governments and pharmaceutical companies.
Lastly, transferability to LMICs will be cross-checked with the support of our partners acting in these regions.
Photo of consortium members at the annual project meeting in 2022