Thesis defense Isaura Wayop

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Antimicrobials are among humanity's most transformative discoveries, significantly extending average life expectancy and revolutionizing modern medicine. However, the emergence of antimicrobial resistance (when bacteria develop the ability to withstand antimicrobials) poses a profound threat. The use of antimicrobials in humans, animals, and the environment is a driver of antimicrobial-resistant pathogens. Without urgent and effective interventions to reduce misuse and overuse of antimicrobials, antimicrobial resistance could become the leading global cause of death and push millions into extreme poverty. Enhancing antimicrobial stewardship and promoting the responsible use of antimicrobials are crucial steps to mitigate the risks of antimicrobial resistance and protect health across all sectors.

In animals, antimicrobials are widely used for therapeutic treatments, disease control (metaphylaxis), and preventive measures (prophylaxis) and as antimicrobial growth promotors to increase the efficiency of animal production. The total volume of antimicrobials used in animals is expected to continue to increase annually. Concerns have arisen about how antimicrobial use in animals may foster antimicrobial resistance, leading to actions such as the ban on growth promotors in European countries. However, antimicrobial use still varies widely between countries, and, for many, data remain unavailable, as most countries do not publicly report their usage.

In the Netherlands, multiple actions taken at private and governmental level to lower veterinary antimicrobial use resulted in an impressive decline in antimicrobial use in livestock. After the first impressive decline however, the decrease curve flattened, and, among other things, veterinary clinical practice guidelines were published to assist veterinarians in practice. Clinical practice guidelines are systematically developed documents created using validated methodologies grounded in the best available evidence. However, data still showed a wide distribution in antimicrobial use on farms – for example, pig farms with weaner pigs.

One of the veterinary clinical practice guidelines introduced to assist veterinarians in managing Streptococcus suis cases deals with Streptococcus suis (S. suis) in weaned pigs (S. suis guideline). The main objective of this guideline is to achieve careful, selective, and responsible use of antimicrobials in cases of clinical S. suis infections in weaned piglets. S. suis is a multifactorial disease, involves treatments of groups of animals, and is one of the major reasons for antimicrobial use in weaned pigs. Results of a survey indicated that the S. suis guideline was used only partly or not at all by most practicing swine veterinarians surveyed, but the extent of use and the elements applied remained unknown.

In human healthcare, it has been widely reported that evidence-based practices and guidelines took years to be incorporated into routine general practice or were not widely adopted at all. Implementation science provides numerous theories, models, and frameworks that are used to promote the systematic uptake of evidence-based practices. Such theories, models, and frameworks offer a structured approach for developing intervention programs facilitating the translation of effective interventions and research evidence into practice, analyzing determinants of implementation outcomes, and evaluating the process and impact of implementation.

The overall objective of this thesis was to develop, implement, and evaluate an intervention program to enhance veterinarians’ adherence to the guideline and ultimately contribute to responsible antimicrobial use in animals. The S. suis guideline was chosen as the prototypical case because 1) it was introduced to the field almost four years before the start of the project and therefore veterinarians and farmers already had experiences with this guideline, 2) its complexity, 3) its low adoption in practice, and 4) the role of S. suis in the total volume of antimicrobials used in weaned pigs in the Netherlands.

A systematic, three-step approach was used to develop an intervention program. In the first step, reasons for veterinarians’ (non-)adherence to the S. suis guideline were explored by qualitative research. Interviews with 13 swine veterinarians and five swine farmers identified six domains relevant to (non-)adherence to the S. suis guideline. These six domains (knowledge, skills, beliefs about capabilities, beliefs about consequences, social influences, and environmental context and resources) were identified using a theory-based framework (Theoretical Domains Framework). Veterinarians reported varied approaches to managing S. suis, with some relying heavily on antimicrobials despite the guideline's emphasis on alternative strategies. This inconsistency underscored the need for targeted interventions to address the gap between evidence-based recommendations and clinical practice and served to develop the objectives of the intervention program.

In the second step, Implementation Mapping was used to design an intervention program that lasted eight months. The resulting program integrated seven evidence-based methods, including modeling, feedback, persuasive communication, and active learning, into activities such as peer-learning and an individual e-learning module. The peer-learning meetings included case discussions, a knowledge quiz, a video of an interview with a practicing swine veterinarian, a video with veterinary specialists and stakeholders, self-evaluation, and feedback based on performance indicators.

In the third step, the performance indicators were developed, using a modified RAND/UCLA method. Performance indicators are measurable items referring to structures, processes, and outcomes of care. The final set encompassed five performance indicators: antimicrobial use, the ratio 1st to 2nd or 3rd choice antimicrobials, the argumentation for using 2nd choice antimicrobials, bacteriological examination including susceptibility testing, and the use of corticosteroids. The performance indicators were used in the intervention program and to assess the effect of the program. The results provided baseline information and demonstrated significant variability in both the qualitative and quantitative aspects of antimicrobial prescriptions among veterinarians managing S. suis-related issues on farms.

The intervention program was implemented and evaluated in a multicenter, pragmatic, stepped-wedge cluster design trial. Of the 49 veterinarians that participated, 33 provided data from 125 S. suis problem farms. A baseline measurement (M0) before the intervention program and two measurements during (M1) and partly after (M2) the intervention program were conducted. A significant reduction in farm-level antimicrobial use of 25% in M1 and 49% in M2 was achieved compared with M0. For the performance indicators at veterinarian level, a significant reduction (−36%) was found for antimicrobial prescription in M2, and a significant increase occurred in argumentation for 2nd choice antimicrobials (M2) and the usage of bacteriological examination (M1). Two other performance indicators (ratio of 1st to 2nd or 3rd choice antimicrobials and corticosteroids) did not change significantly. These results suggest that implementing a multifaceted intervention program to promote compliance to existing veterinary guidelines can enhance antimicrobial stewardship among veterinarians.

This study demonstrates the potential for similar interventions for veterinary guidelines globally. The structured approach to intervention development, including stakeholder involvement and systematic planning, serves as a model for future initiatives. Integrating guideline-based intervention programs into postgraduate veterinary education can further enhance veterinarians’ expertise and professionalism. More research is needed into the effectiveness of multilevel veterinary antimicrobial stewardship programs based on theory, models, and/or frameworks, rather than focusing solely on the individual level.

In conclusion, our intervention program successfully enhanced veterinarians’ adherence to the guideline on S. suis in weaned pigs, resulting in a lower level of antimicrobial prescriptions by veterinarians, and thereby supported antimicrobial stewardship on farms with S. suis problems. Core elements of the success of this theory-based antimicrobial stewardship intervention program included the One Health approach, the use of a theoretical framework, a systematic methodology, and performance indicators. To maximize the impact of clinical practice guidelines, a tailored intervention program is essential for each guideline. To save time and reduce costs, our findings can serve as a foundation for developing similar implementation strategies in other countries, ultimately enhancing antimicrobial stewardship in veterinary medicine.