# Combining demographic shifts with age-based resistance prevalence to estimate future antimicrobial resistance burden in Europe and implications for targets: A modelling study

## TL;DR

This study models how demographic changes and age-related resistance patterns will affect future drug-resistant infections in Europe, showing that ignoring age and sex leads to inaccurate projections.

## Contribution

The study introduces a novel approach combining demographic shifts with age- and sex-specific resistance data to project future AMR burdens in Europe.

## Key findings

- BSI incidence rates are projected to increase more in men and older adults across most bacteria.
- Ignoring age and sex leads to underestimating resistance burden in men and older populations.
- Achieving a 10% reduction in resistant BSI incidence by 2030 is only feasible for 68.4% of bacteria-antibiotic combinations.

## Abstract

Antimicrobial Resistance (AMR) is a global public health crisis. Evaluating intervention impact requires accurate estimates of how the AMR burden will change over time, given likely demographic shifts. This study aimed to provide an estimate of future AMR burden in Europe, investigating resistance variation by age and sex and the impact of interventions to achieve the proposed United Nations (UN) political declaration targets.

Using data from 12,807,473 bloodstream infection (BSI) susceptibility tests from routine surveillance in Europe, we estimate age- and sex-specific rates of change in BSI incidence for the 8 bacteria included in European Antimicrobial Resistance Surveillance Network (EARS-Net) surveillance over 2015–2019. This was used to project incidence rates by age and sex for 2022–2050 and, with demographic projections, to generate estimates of BSI burden (2022–2050). Two Bayesian hierarchical models were fitted across 38 bacteria-antibiotic combinations to the 2015–2019 resistance proportion of BSI by year and at the country-level with and without age and sex disaggregation. Inputting the incidence estimates into the “agesex” and “base” model, respectively, we sampled 1,000 model estimates of resistant BSI burden by age, sex, and country to determine the importance of age and sex disaggregation. We explored Intervention scenarios consisting of a 1, 5, or 20 per 100,000 per year reduction in infection incidence rate of change or 5 per 100,000 per year reduction in those older than 64 years.

Overall, in Europe, BSI incidence rates are predicted to increase more in men than women across 6 of the 8 bacteria (Pseudomonas aeruginosa and Enterococcus faecium were the exception) and are projected to increase more dramatically in older age groups (74+ years) but stabilise or decline in younger age groups. We project huge country-level variation in resistance burden to 2050, with opposing trends in different countries for the same bacteria-antibiotic combinations (e.g., aminoglycoside-resistant Acinetobacter spp. ranged from a relative difference of 0.34 to 15.38 by 2030).

Not accounting for age and sex results in differing resistance burden projections, with 47% of bacteria-antibiotic combinations estimated to have fewer resistant BSIs by 2030 compared to a model with age and sex. Not including age or sex resistance patterns results in fewer male cases for 76% (29/38) of the combinations compared to 11% (4/38) for women. We also saw age-based associations in projections with bigger differences at older ages.

Achieving a 10% reduction in resistant BSI incidence by 2030 (equivalent to the UN 10% mortality target) was possible only for 68.4% (26/38) of bacteria-antibiotic combinations even with large reductions in BSI incidence rate of change of −20 per 100,000 per year. In some cases, a 10% reduction was followed by a rebound, with the resistant BSI burden exceeding previous levels by 2050. Limitations include reliance on European data and current trends, and the exclusion of factors such as comorbidities or ethnicity.

Including country-specific, age- and sex-specific resistance levels alongside projected demographic shifts has a large impact on resistant BSI burden projections in Europe to 2030. Reducing this AMR infection burden by 10% will require substantial reductions in infection incidence rates.

Infections caused by bacteria that are resistant to antibiotics are a major and growing threat to public health.

Older adults and men are at higher risk of serious infections, but most estimates of the future burden of drug-resistant infections do not consider how populations are ageing or how infection risk varies by sex.

Global targets aim to reduce deaths from drug-resistant infections by 10% by 2030 compared with a 2019 baseline, but it is unclear whether this is achievable.

The researchers analysed data from over 12 million blood tests for bacterial infections in 29 European countries between 2010 and 2019.

They used these data to predict how rates of serious bacterial infections and the number of drug-resistant bloodstream infections may change in the future (to 2050), considering age, sex, and population changes.

Their models show that the burden of drug-resistant bloodstream infections varies substantially by country and by bacteria-antibiotic combination.

Predictions that do not take age and sex into account may miss a large part of the future burden—especially among men and older adults.

Even with strong public health actions, reducing the rate of bloodstream infection by 10% will be hard to achieve for several bacteria-antibiotic combinations.

Future plans to tackle drug-resistant infections must account for context-specific changes in population demographics and differences in infection rate and drug-resistance burden by age and sex.

Given projected increases in infections across most countries and bacteria–antibiotic combinations, simply achieving a plateau in the burden of antibiotic-resistant infections would represent meaningful progress.

These predictions are based on current trends and data from Europe, and may not apply in the same way elsewhere. They also do not include all risk factors, such as underlying health conditions or ethnicity, and should be interpreted with caution.