The relationship between antibiotic use in humans and poultry and antibiotic resistance prevalence in humans: an ecological regression study of Campylobacter in the UK

Antibiotic resistance (ABR), the capacity of bacterial pathogens to survive in the presence of antibiotics, is an increasingly pressing issue for human health worldwide. The use of antibiotics (ABU) in humans and livestock animals, is considered the main driver of the global increase in ABR prevalence, but the shape and size of this relationship at the population level is still uncertain. In the UK, the bacterial pathogen Campylobacter is a major cause of foodborne infection, with most infections attributed to poultry. It is a strong case study to investigate the ecological relationship between antibiotic use and resistance across humans and animals. Despite significant reductions in ABU in humans and poultry over the last decade, the rate of ABR in Campylobacter infections in the UK has remained relatively high. We compiled data on Campylobacter infections and the use of antibiotics in primary care, secondary care, and poultry health in the UK from 2011 to 2022 (human data were from England only). Using pooled ordinary least squares regression, we investigated the relationship between the rate of ABR in Campylobacter infections and the quantity of ABU in each of these three sectors. We also explored the shape and size of this relationship using different specifications. Our results suggest that the rate of antibiotic resistance in human Campylobacter infections in the UK was positively linked with use of antibiotics in humans, with some evidence that it was also linked to antibiotic use in poultry. However, antibiotic use explained only a relatively small portion of the changes in resistance. For human health, we found evidence that the relationship between (antibiotic) use and resistance weakens over time as resistance builds up in the human population, supporting the idea of a resistance threshold beyond which resistant strains become endemic and reductions in use become less effective. Our results suggest that reducing use alone may not be sufficient to bring the level of ABR in Campylobacter down to desirable levels. While antibiotic stewardship remains essential, future policy and research on Campylobacter should dedicate focus to transmission factors, safeguarding new antibiotics in people, and alternative and complementary therapies for poultry infection such as vaccination and bacteriophages. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) under grant no. JPIAMR2021-182 SEFASI ### 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 ethics committee of The London School of Hygiene and Tropical Medicine gave ethical approval for this work 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 were obtained upon request or application from the UK Health Security Agency (UKHSA) and British Poultry Council (BPC), and are not publicly available. They are therefore not available upon request from the authors.