Antimicrobial resistance prevalence in bloodstream infection in 29 European countries by age and sex: An observational study.

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. This study aimed to address this knowledge gap by quantifying how resistance prevalence and incidence of bloodstream infection (BSI) varied by age and sex across bacteria and antibiotics in Europe. Methods and findings: We used patient-level data collected as part of routine surveillance between 2015 and 2019 on BSIs in 29 European countries from the European Antimicrobial Resistance Surveillance Network (EARS-Net). A total of 6,862,577 susceptibility results from isolates with age, sex, and spatial information from 944,520 individuals were used to characterise resistance prevalence patterns for 38 different bacterial species and antibiotic combinations, and 47% of these susceptibility results were from females, with a similar age distribution in both sexes (mean of 66 years old). A total of 349,448 isolates from 2019 with age and sex metadata were used to calculate incidence. We fit Bayesian multilevel regression models by country, laboratory code, sex, age, and year of sample to quantify resistant prevalence and provide estimates of country-, bacteria-, and drug-family effect variation. We explore our results in greater depths for 2 of the most clinically important bacteria–antibiotic combinations (aminopenicillin resistance in Escherichia coli and methicillin resistance in Staphylococcus aureus) and present a simplifying indicative index of the difference in predicted resistance between old (aged 100) and young (aged 1). At the European level, we find distinct patterns in resistance prevalence by age. Trends often vary more within an antibiotic family, such as fluroquinolones, than within a bacterial species, such as Pseudomonas aeruginosa. Clear resistance increases by age for methicillin-resistant Staphylococcus aureus (MRSA) contrast with a peak in resistance to several antibiotics at approximately 30 years of age for P. aeruginosa. For most bacterial species, there was a u-shaped pattern of infection incidence with age, which was higher in males. An important exception was E. coli, for which there was an elevated incidence in females between the ages of 15 and 40. At the country-level, subnational differences account for a large amount of resistance variation (approximately 38%), and there are a range of functional forms for the associations between age and resistance prevalence. For MRSA, age trends were mostly positive, with 72% (n = 21) of countries seeing an increased resistance between males aged 1 and 100 years and a greater change in resistance in males. This compares to age trends for aminopenicillin resistance in E. coli which were mostly negative (males: 93% (n = 27) of countries see decreased resistance between those aged 1 and 100 years) with a smaller change in resistance in females. A change in resistance prevalence between those aged 1 and 100 years ranged up to 0.51 (median, 95% quantile of model simulated prevalence using posterior parameter ranges 0.48, 0.55 in males) for MRSA in one country but varied between 0.16 (95% quantile 0.12, 0.21 in females) to −0.27 (95% quantile −0.4, −0.15 in males) across individual countries for aminopenicillin resistance in E. coli. Limitations include potential bias due to the nature of routine surveillance and dependency of results on model structure. Conclusions: In this study, we found that the prevalence of resistance in BSIs in Europe varies substantially by bacteria and antibiotic over the age and sex of the patient shedding new light on gaps in our understanding of AMR epidemiology. Future work is needed to determine the drivers of these associations in order to more effectively target transmission and antibiotic stewardship interventions. Naomi R Waterlow and colleagues leverage data from 29 countries across Europe to determine how antimicrobial resistance varies by age and sex. Author summary: Why was this study done?: Antimicrobial resistance (AMR) is a major global public health threat, but little is known about how the prevalence of resistance varies with age and sex. What did the researchers do and find?: We explored patterns of resistance prevalence and incidence by age and sex in routinely collected data from bloodstream infections (BSIs) across Europe for 8 bacterial species. We fitted a Bayesian multilevel regression model to quantify the variation nationally and subnationally. Distinct patterns in resistance prevalence by age were observed across Europe for different bacteria. Sex was often only weakly associated with resistance, except across ages in Escherichia coli and Klebsiella pneumoniae, and at younger ages for Acinetobacter species, where it was higher in males. What do these findings mean?: These findings highlight important gaps in our knowledge of the epidemiology of AMR that are difficult to explain through known patterns of antibiotic exposure and healthcare contact. Differences in AMR burden by age and sex may be explained by cultural differences between countries as well as variation in pathways to infection between bacteria. Our findings suggest that there may be value in considering interventions to reduce AMR burden that take into account important variations in AMR prevalence with age and sex. This study is limited by the nature of routine surveillance, the lack of open availability of disaggregated data, and the model structures explored. [ABSTRACT FROM AUTHOR]