How, why and when are delayed (back-up) antibiotic prescriptions used in primary care? A realist review integrating concepts of uncertainty in healthcare

Background: Antimicrobial resistance is a global patient safety priority and inappropriate antimicrobial use is a key contributing factor. Trials have shown that delayed (back-up) antibiotic prescriptions (DP) are an effective and safe strategy for reducing unnecessary antibiotic use but its uptake is controversial. Methods: We conducted a realist review (a literature review which goes beyond assessing whether an intervention works) to ask why, how, and in what contexts general practitioners (GPs) use DP. The review is focused on those who wish to use DP and not for those who are against using DP. We searched five electronic databases for relevant articles and included DP-related data from interviews with healthcare professionals in a related study. Data were analysed using a realist theory-driven approach - theorising which context(s) influenced (mechanisms) resultant outcome(s) (context-mechanism-outcome-configurations: CMOCs). Results: Data were included from 76 articles and 41 interviews to develop a program theory comprising nine key and 56 related CMOCs. These explain the reasons for GPs' tolerance of risk to different uncertainties: epistemological (knowledge-orientated); scientific (data-orientated); hermeneutic (interpretation-orientated); practical (structures/processes-orientated); technological (skills/software/equipment-orientated), and existential (world-view-orientated). These interact with GPs' work environment, self-efficacy and perceived patient concordance to make using DP as a safety-net or social tool more or less likely, at a given time-point. Our program theory explains how DP can be used to mitigate some uncertainties but also provoke or exacerbate others. Conclusion: This review explains how, why and in what contexts GPs are more or less likely to use DP, as well as various uncertainties GPs face which DP may mitigate or provoke. We recommend that efforts to plan and implement interventions to optimise antibiotic prescribing in primary care should consider these uncertainties and the contexts when DP may be (dis)preferred over other interventions to reduce antibiotic prescribing. We also recommend the following and have included example activities for: (i) reducing demand for immediate antibiotics; (ii) framing DP as an 'active' prescribing option; (iii) documenting the decision-making process around DP; and (iv) facilitating social and system support. ### Competing Interest Statement BH works for eConsult, a provider of asynchronous consultations in primary, secondary, and urgent/emergency care. Other authors declare no conflict of interest. ### Funding Statement The study was funded by the Economic and Social Research Council (ESRC) through the Antimicrobial Resistance Cross Council Initiative supported by the seven research councils in partnership with other funders (grant reference: ES/P008232/1) and supported by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford (NIHR200915) and Imperial College London (NIHR200876) in partnership with the UK Health Security Agency (UKHSA), the NIHR Oxford Biomedical Research Centre and the NIHR Imperial Patient Safety Translational Research Centre (PSTRC-2016-004). The support of the funders is gratefully acknowledged. The funders played no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the UKHSA or the UK Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Oxford research ethics committee (ref. R59812) and NHS Health Research Authority (ref. 19/HRA/0434) approved the qualitative study conducted by our STEP-UP team that was published elsewhere. The approval included use of interview transcripts as part of the STEP-UP program. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors