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.