Periodic Reporting for period 2 - REVERSE (pREVention and management tools for rEducing antibiotic Resistance in high prevalence Settings)
Okres sprawozdawczy: 2023-01-01 do 2024-06-30
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.
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.
For brevity, tasks within a Work Package (WP) are summarised together with details in the technical report.
WP1 is responsible for trial management in the 24 participating hospitals. During this reporting period, data collection continued in the database hosted by the University Hospital Zürich (Task 1.3). All cohorts have finished the MDS intervention and started the IPC intervention; the first cohort has started already the ABS intervention (Task 1.5). All hospitals are reporting process indicators for the interventions. 6 of the 8 planned pre-intervention workshops have taken place. (Task 1.4).
WP2 is responsible for the MDS intervention, outbreak analysis, and repeated point prevalence surveys (PPS) of MDRO carriage. Work completed during this reporting period includes the reassessment of the microbiology and diagnostic stewardship capacity of every hospital (Task 2.1) outbreak characterisation four hospitals (Task 2.2) and analysis of the first round of MDRO-PPS (Task 2.3).
WP3 is responsible for the IPC intervention. Work completed during this period includes finalisation of the WP3 narrative synthesis and development of the IPC SOPs (Standard Operating Procedures) for the 24 hospitals (Task 3.1) start of the IPC intervention in all 24 hospitals with ongoing monitoring of process indicators (Task 3.2). WP3 also developed an online serious game to increase knowledge surrounding AMR, MDRO and IPC interventions.
WP4 is responsible for the ABS intervention. During this period, the ABS protocol was developed and cohort 1 started the ABS intervention (Task 4.2). Protocols and the database for the advanced tasks (Task 4.3-4.6) were also finalised and the hospitals appointed. These tasks are currently in the baseline period.
WP5 monitors and supports the Implementation of the IPC and ABS programmes in the REVERSE hospitals. Site visits prior to the implementation of IPC and ABS in the ENHANCED sites were completed in all four countries (Task 5.2; supported by WPs 1, 3, 4). Implementation workshops were organised for each cohort as an in-person 1.5 day event (Task 5.3 supported by WPs 1, 3, 4, 7) with ongoing implementation support for the ENHANCED sites after the workshop. Work has started on Tasks 5.4 and 5.5 (Data Analysis and Summative Evaluation).
WP6 is responsible for the cost effectiveness layer of REVERSE. The systematic review updating the evidence on cost-effectiveness of IPC and ABS interventions is almost complete (Task 6.1). Micro-costing plans are being developed and the nested Quality of Life study is recruiting in all four countries (Task 6.2). Models have been developed to assess cost-effectiveness from the hospital perspective (Task 6.3) and the groundwork has been laid to extrapolate the REVERSE findings to LMICs (Task 6.6).
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. An updated PDE was submitted (Task 7.4) and the Ethics deliverables due during this reporting period were also submitted (Task 7.5). A meeting to update the external stakeholder panel was organised in June 2023 (Task 7.6). We expanded our webpage, and increased our reach through social media and email newsletters (Task 7.7).
WP8 is responsible for the ethics requirements. All deliverables due this reporting period were submitted as part of Task 7.5.
WP1 is responsible for trial management in the 24 participating hospitals. During this reporting period, data collection continued in the database hosted by the University Hospital Zürich (Task 1.3). All cohorts have finished the MDS intervention and started the IPC intervention; the first cohort has started already the ABS intervention (Task 1.5). All hospitals are reporting process indicators for the interventions. 6 of the 8 planned pre-intervention workshops have taken place. (Task 1.4).
WP2 is responsible for the MDS intervention, outbreak analysis, and repeated point prevalence surveys (PPS) of MDRO carriage. Work completed during this reporting period includes the reassessment of the microbiology and diagnostic stewardship capacity of every hospital (Task 2.1) outbreak characterisation four hospitals (Task 2.2) and analysis of the first round of MDRO-PPS (Task 2.3).
WP3 is responsible for the IPC intervention. Work completed during this period includes finalisation of the WP3 narrative synthesis and development of the IPC SOPs (Standard Operating Procedures) for the 24 hospitals (Task 3.1) start of the IPC intervention in all 24 hospitals with ongoing monitoring of process indicators (Task 3.2). WP3 also developed an online serious game to increase knowledge surrounding AMR, MDRO and IPC interventions.
WP4 is responsible for the ABS intervention. During this period, the ABS protocol was developed and cohort 1 started the ABS intervention (Task 4.2). Protocols and the database for the advanced tasks (Task 4.3-4.6) were also finalised and the hospitals appointed. These tasks are currently in the baseline period.
WP5 monitors and supports the Implementation of the IPC and ABS programmes in the REVERSE hospitals. Site visits prior to the implementation of IPC and ABS in the ENHANCED sites were completed in all four countries (Task 5.2; supported by WPs 1, 3, 4). Implementation workshops were organised for each cohort as an in-person 1.5 day event (Task 5.3 supported by WPs 1, 3, 4, 7) with ongoing implementation support for the ENHANCED sites after the workshop. Work has started on Tasks 5.4 and 5.5 (Data Analysis and Summative Evaluation).
WP6 is responsible for the cost effectiveness layer of REVERSE. The systematic review updating the evidence on cost-effectiveness of IPC and ABS interventions is almost complete (Task 6.1). Micro-costing plans are being developed and the nested Quality of Life study is recruiting in all four countries (Task 6.2). Models have been developed to assess cost-effectiveness from the hospital perspective (Task 6.3) and the groundwork has been laid to extrapolate the REVERSE findings to LMICs (Task 6.6).
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. An updated PDE was submitted (Task 7.4) and the Ethics deliverables due during this reporting period were also submitted (Task 7.5). A meeting to update the external stakeholder panel was organised in June 2023 (Task 7.6). We expanded our webpage, and increased our reach through social media and email newsletters (Task 7.7).
WP8 is responsible for the ethics requirements. All deliverables due this reporting period were submitted as part of Task 7.5.
The REVERSE trial assess 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.
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.