Examining tailoring as an implementation strategy for reducing healthcare-associated infections across European acute care hospitals (REVERSE): study protocol for a hybrid type 2 effectiveness-implementation trial

Background: Infection prevention and control (IPC) and antibiotic stewardship (ABS) represent promising approaches for reducing the prevalence of healthcare-associated infections (HAI) and antimicrobial resistance (AMR) in different healthcare settings. However, the combined use of IPC and ABS measures and ways to optimize their integrated implementation have been insufficiently considered and assessed. The REVERSE trial, funded by the European Union's Horizon 2020 program, involves 24 acute care hospitals from four European countries, all with high rates of AMR and HAI. REVERSE aims to investigate whether the sequential implementation of an IPC and an ABS practice bundle is feasible and sustainable and whether externally guided tailoring as an enhanced implementation strategy leads to superior clinical and implementation outcomes compared to a basic implementation condition. Methods: REVERSE will be designed as a stepped wedge cluster randomized, hybrid type 2 trial, including an embedded implementation trial. Four cohorts of six acute care hospitals will sequentially enter the trial over 38 months and work to implement first IPC, and, after 1 year, add the ABS practice bundle. Simultaneously, hospitals will be provided basic implementation training and instructed to tailor their implementation, with half of the hospitals being self-guided in their tailoring, whereas hospitals in the enhanced implementation condition will receive time-limited external facilitation in practicing tailoring. Qualitative data will be collected longitudinally to investigate contextual conditions for implementing IPC and ABS locally and how they contribute to tailoring results. IPC and ABS feasibility, fidelity, and sustainability will be assessed together with tailoring fidelity using repeated measures. Retrospective, in-depth, explanatory case studies will be conducted to interpret hospital outcomes. Discussion: REVERSE is an extensive and complex effectiveness-implementation trial aimed at investigating tailoring effectiveness. It will contribute to the still scarce evidence base for this adaptive approach to integrating research-supported interventions into routine healthcare settings. By identifying pathways toward strengthening the integration of IPC and ABS practices at European acute care hospitals, REVERSE also has the potential to inform much-needed concerted efforts to combat the growing challenge of antimicrobial resistance in the region. Trial registration: In November 2021, the REVERSE study was registered with the "International Standard Randomised Controlled Trial Number" (ISRCTN) register under nr.12956554.