Implementation of procalcitonin-guided antibiotic stopping advice in sepsis: A mixed-methods process evaluation in a clinical trial context

Background: Appropriate antibiotic use can save life in sepsis while reducing the risk of bacterial resistance. Biomarkers, such as procalcitonin (PCT), can inform the timing of the clinical decision to stop a course of antibiotics. The recently reported multicentre ADAPT-Sepsis trial showed that a daily PCT-guided protocol can safely reduce the duration of antibiotic use in people with suspected sepsis. This linked study aimed to identify potential barriers and facilitators to implementation of PCT testing. Methods: This process evaluation collected qualitative and quantitative data from clinical teams involved in the delivery of adapt-sepsis. Trial site staff were invited to complete a questionnaire and to participate in a semistructured interview. Responses were thematically analysed and compared with constructs from the Consolidated Framework for Implementation Research (CFIR v2.0). Results: A total of 69 staff from 26 critical care units responded to the online questionnaire ( n = 55); the interview invitation ( n = 3); or both ( n = 11). Interviewees included critical care consultants, junior doctors, and research nurses. At least 60% of ADAPT-Sepsis trial staff respondents supported the continuation of PCT testing, even before trial results were publicised. Several of the implementation facilitators related to factors evident at the level of the site/organisation, such as microbiology involvement and increasing access to knowledge and information about evidence supporting the tests. Cost was raised as a potential barrier. Conclusion: Adoption of biomarker tests such as PCT may be facilitated by communicating high-quality evidence, supported by staff focussed on antimicrobial stewardship. Cost implications have been considered in a related economic analysis. Study registration: This study was prospectively registered online. The unique identifying number at researchregistry.com is researchregistry4244.