How a radical approach is to slow down the increase of antibiotic-resistant pathogens in Europe and whether this can succeed. An interview with Walter Zingg, Head of Hospital Hygiene at the University Hospital Zurich.

«We see that the development of antibiotic resistance has worsened in recent years, especially in countries in southern and south-eastern Europe, and that little is being done to combat it in hospitals there,» Walter Zingg states when we meet him for an interview in his office on the edge of the university quarter. The infectiologist and Head of Hospital Hygiene at the University Hospital Zurich knows the problem first-hand. On behalf of the ECDC^[1], he regularly takes part in country visits and evaluates the antibiotic resistance situation and infection prevention in hospitals. Especially intensive care units, where hundreds of people are treated every day, are hotspots for the development of resistance. Multi-resistant bacteria spread in and beyond the hospitals into the population if the clinics do not counteract this with rigorous hospital hygiene measures. But hospitals in southern and eastern Europe often lack the resources, the know-how, the infrastructure and also the awareness to enforce effective hospital hygiene and the targeted use of antibiotics.

«The idea is that
during the four years
of the project
the hospitals will
undergo a cultural
change.»

Switzerland is still a kind of island, but with every repatriated person admitted to a Swiss hospital from a country with a high prevalence, the pressure increases that multidrug-resistant bacteria will also become more common here, says Walter Zingg, describing the situation. «We check these patients when they come in, make sure that there are no infections, and we are doing quite well.» But it has long been clear to him and his colleagues in the Swiss hospital hygiene community that something has to be done in countries with high antibiotic resistance. «The idea of conducting a large clinical trial on antibiotic resistance in high-prevalence countries, involving comprehensive interventions in hospital hygiene and antibiotic use, has been on our minds for some time. The problem was funding,» explains Walter Zingg.

But then, unexpectedly, an opportunity presented itself in 2020. As part of Horizon 2020, the European Commission published a call for projects on new approaches to the clinical management and prevention of resistant bacterial infections in high-prevalence areas. Walter Zingg and his colleagues did not hesitate. Immediately, they assembled a consortium of experts from twelve European university hospitals, research institutions and health services as well as 24 associated hospitals, wrote a project proposal and were awarded the contract. In July 2021, the project started with the programmatic title REVERSE.

Ambitious aim

«Ultimately, the aim is to reverse or at least stabilise the development of resistance in 24 hospitals of high prevalence areas through comprehensive interventions,» is how Walter Zingg succinctly describes REVERSE’s goal. To this end, he and his team have developed a sophisticated project structure that skilfully combines knowledge transfer, behavioural change and knowledge gain. The core is formed by interventions in three key areas of contemporary hospital hygiene: diagnostics, infection prevention and targeted use of antibiotics (antibiotic stewardship). In concrete terms, these interventions work as follows: In six selected hospitals in Spain, Italy, Greece and Romania, procedures, processes and rules of conduct for the prevention and management of infections are implemented that reflect the latest knowledge and experience. However, the participating hospitals do not simply receive a manual of measures and a few instructions for implementation. They have to actively develop strategies and concepts themselves on how to implement the state-of-the-art measures and processes, tailored to their possibilities and needs. They are supported by interdisciplinary teams from the project consortium.

Challenging implementation

The 24 hospitals, six each in Greece, Italy, Romania and Spain, were randomly divided into four groups (cohorts). Each group comprises six hospitals, with at least one hospital from each country. Each of these four groups goes through the three intervention steps in a staggered order. Group 1 started in autumn 2022 with the diagnostic intervention. Three months later, in January 2023, group 2 began the diagnostic intervention, followed at three-month intervals by groups 3 and 4. Once a group has completed one intervention phase, it starts the next. For example, Group 1 completed its diagnostic intervention in March 2023 and started its infection prevention intervention. In spring 2024, group 1 will then start the third and final intervention in the area of antibiotic stewardship, while groups 2, 3 and 4 will still be in different sections of the infection prevention intervention at that time. All four groups undergo the same programme in the same order; only the time when the interventions start is randomised. At the same time, all hospitals collect data on the infection situation. From this, a later analysis on whether the infection situation has improved after the interventions can be conducted. A few months before the start, the groups are prepared for the respective intervention and have to provide the project management with data and information that are relevant for the intervention area in question and important for the later evaluation. In the area of prevention, the clinics collect up-to-date information on the organisation of infection prevention in their hospital before the start and at the end of the intervention and feed this into the project database.

«We see that in
southern and south-eastern
Europe the development
of antibiotic resistance
has worsened.»

The intervention phases start with a kick-off event for each of the four groups. For the area of diagnostics and antibiotic stewardship, this was done via Zoom. For the area of infection prevention, the project management conducts a workshop lasting several days, during which the representatives of the clinics meet in person, receive information and exchange ideas. They then set about developing concepts on how infection prevention measures such as hand hygiene can be effectively implemented in their clinic and put them into practice. Experts from the project team support and advise them in this process. Of course, the measures are continued even after the intervention has been completed. They should become part of everyday hospital life. Whether this actually happens will be seen at the end of the project, when all four groups have gone through all three interventions.

Open results

REVERSE is a highly complex project with twelve partner organisations, 24 hospitals in four countries, around 100 participants and a matrix structure of test clinics and specialist groups. The project managers Ashlesha Sonpar and Jessie Zheng ensure that it runs as smoothly as possible – and very successfully. Coordinator Walter Zingg sums up the performance of his two project managers, «Ash and Jessie are doing a super job. They make sure that the hospitals stay on track, that the exchange between all project participants works, that no one suddenly does anything out of plan, and that everyone works in coordination with each other.»

REVERSE will end in three years. We ask Walter Zingg what has to be fulfilled by then for the project to be completed successfully. «From the coordinator’s perspective, I am happy when I see that the hospitals have entered all data so we have a complete data set that can be statistically evaluated. Then we can make a scientifically sound statement about whether it is possible to improve the resistance situation with comprehensive interventions in hospitals with a high prevalence. Our study is open-ended. Of course, we would like to be able to say to the European Commission, ‘Yes, it is possible. But you have to put a lot of money into it.’ But we might also have to tell the Commission that it is not possible because the hospitals are overstretched. Depending on the outcome of REVERSE: In the end, politics must draw the conclusion.»

[1] ECDC: European Centre for Disease Prevention and Control» is a public health agency of the EU.