Temporal trends and drivers of antibiotic failure in the general population

Background: Antimicrobial resistance is a serious and growing concern for health systems worldwide. Although the link between antimicrobial use and resistance is well-established, this association is complex and much remains unknown about the exact drivers of antimicrobial resistance. Aim: to investigate temporal trends of first-line antibiotic failures in the general population as well as possible risk factors associated with increased incidence of first-line antibiotic failures, by type of infection and antibiotic class. Methods: Analyses will be performed on one of the largest and richest datasets available for research purposes in the world - anonymised electronic health records with >100 million patient-years from 1995 to 2020 from the Clinical Practice Research Datalink (CPRD). Risk factor analyses will investigate clinical (eg. concomitant treatment with unrelated drugs), demographic (eg. socioeconomic status) and behavioural (eg. smoking) risk factors, many of which have not been formally investigated so far. Expected Outcomes: A better understanding of the factors associated with antibiotic failures in routine clinical practice may inform the development of more targeted and effective prevention measures to limit the emergence of antimicrobial resistance. Identified risk factors as well as differences between infection types and antibiotic classes may further point towards biological functions underlying these complications and inform the design of future research.