The three-armed cluster-randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%; arm II 9.9%; arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care. Trial registration: ISRCTN, ISRCTN58150046

The cluster randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance, 2017-2020) promoted the appropriate use of antibiotics for acute non-complicated infections in primary care networks (PCNs) in Germany. A process evaluation aimed to provide insights into determinants of practice and explored factors associated with antibiotic prescribing patterns. In a nested mixed-methods approach, a three-waves survey used study-specific questionnaires for participating physicians and medical assistants to assess potential impacts and uptake of the complex intervention program. Stakeholders received a one-time online questionnaire to reflect on network-related aspects. Semi-structured, open-ended interviews with a purposive sample of physicians, medical assistants and stakeholders explored aspects regarding the acceptance of the program components for daily practice and the perceived sustainability of intervention component effects. The intervention components were perceived to be smoothly integrable into practice routines. The highest uptake was reported for the educational components: feedback reports, background information, e-learning modules, and disease specific quality circles. Participation in PCNs was seen as motivational factor for guideline-oriented patient care and the adoption of new routines Future approaches to fostering appropriate use of antibiotics by targeting health literacy competencies and clinician’s therapy decisions should combine evidence-based information sources, audit and feedback reports and QCs.