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

Abstract

BackgroundAntibiotic 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.ResultsAt 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 resistantS. aureus(MRSA) contrast with a peak in resistance to several antibiotics at ∼30 years of age forP. aeruginosa.This diverges from the known, clear exponential increase in infection incidence rates by age, which are higher for males except forE. coliat 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 inE. coliwhich 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 inE. coli.ConclusionPrevalence 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.

Diverse Relationships Between Antibiotic Resistance and Host Age: A Meta-Analysis Across Antibiotic Classes and Bacterial Genera

“…Finally, some studies suggest that the frequency of resistance mutations within the host gut microbiome increase with age [18][19][20] . Such mutations have the potential of being transferred to pathogenic bacteria via horizontal gene transfer (HGT), thus increasing the likelihood of resistant infections 21,22 A recent pre-print, specifically analysing bloodstream infections in Europe for the limited number of antibiotic-pathogen combinations monitored by the ECDC, has also indicated potential associations between AMR probability and age, with varying patterns across antibiotics and bacteria 23 .…”