How demographic factors matter for antimicrobial resistance – quantification of the patterns and impact of variation in prevalence of resistance by age and sex.

Background Antibiotic usage, contact with high transmission healthcare settings as well as changes in immune system function all vary by a patient’s age and sex. Yet, most analyses of antimicrobial resistance (AMR) ignore demographic indicators and provide only country level resistance prevalence values.   In this work we use routine surveillance data on serious infections in Europe to characterise the importance of age and sex on incidence and resistance prevalence patterns for 33 different bacteria and antibiotic combinations. We fit Bayesian multilevel regression models to quantify these effects and provide estimates of country-, bacteria- and drug-family effect variation.     Results At the European level, we find distinct patterns in resistance prevalence by age that have previously not been explored in detail. Trends often vary more within an antibiotic family than within a bacterium: clear resistance increases by age for methicillin resistant S. aureus (MRSA) contrast with a peak in resistance to several antibiotics at ~30 years of age for P. aeruginosa. This diverges from the known, clear exponential increase in infection incidence rates by age, which are higher for males except for E. coli at ages 15-40.   At the country-level, the patterns are highly context specific with national and subnational differences accounting for a large amount of resistance variation (~38%) and a range of associations between age and resistance prevalence. We explore our results in greater depths for two of the most clinically important bacteria–antibiotic combinations. For MRSA, age trends were mostly positive, with 72% of countries seeing an increased resistance between males aged 1 and 100 and more resistance in males. This compares to age trends for aminopenicillin resistance in E. coli which were mostly negative (males: 93% of countries see decreased resistance between ages 1 and 100) with more resistance in females. A change in resistance prevalence between ages 1 and 100 ranged up to ~0.46 (95% CI 0.37 – 0.51, males) for MRSA but varied between 0.16 (95% CI 0.23-0.3, females) to -0.27 (95%CI -0.4 - -0.15, males) across individual countries for aminopenicillin resistance in E. coli.   Conclusion Prevalence of resistance in infection varies substantially by the age and sex of the individual revealing gaps in our understanding of AMR epidemiology. These context-specific patterns should now be exploited to improve intervention targeting as well as our understanding of AMR dynamics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement GMK, MR/W026643/1, Medical Research Council UK, https://www.ukri.org/opportunity/career-development-award/, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### 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: LSHTM ethics review board. 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 Patient level data is available upon request from the European Antimicrobial Resistance Surveillance Network (EARS-Net) from the Surveillance System (TESSy) for those who meet the criteria for access to confidential data. https://www.ecdc.europa.eu/en/publications-data/european-surveillance-system-tessy.