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Antimicrobial resistance linked to patients’ age and sex, pan-European study finds

Age and sex are associated with a patient’s likelihood of developing antimicrobial resistance, a new pan-European study has revealed.

Researchers from the London School of Hygiene and Tropical Medicine (LSHTM) found distinct patterns in antimicrobial resistance that correlated with a person’s age, sex, and location in Europe.

Most bacterial species were found to have higher incidence in younger and older age groups, but resistance varied by antibiotic family and also by geographical region. 

Overall, males are more likely than females to be resistant to antibiotics, and in some cases, such as Staphylococcus aureus (MSRA), methicillin-resistant infection increased with age.

The researchers hope the findings, published in the journal PLOS Medicine, will reduce the emergence of antibiotic resistance and preserve antibiotic efficacy in the future.

Antimicrobial resistance is a major global public health threat, but little is known about how the prevalence of resistance varies with age and sex.

The researchers analysed patient-level data collected as part of routine surveillance between 2015 and 2019 on bloodstream infections from the European Antimicrobial Resistance Surveillance Network (EARS-Net).

Over 6.5 million isolates were collected from 944,520 individuals (47% female, mean age of 66 years) across 29 European countries, and susceptibility results across 38 different bacterial species and antibiotic combinations, using eight bacterial species, were analysed for resistance.

In 349,448 isolates, the findings were correlated with age and sex metadata collected in 2019. Bayesian multilevel regression models were employed to account for any variations in incidence rates across countries, laboratories, sex, age and year of sample to quantify prevalence of resistance and provide estimates of how country, bacteria and drug family affected variation.

Two of the most clinically important bacteria–antibiotic combinations were analysed in greater depth: aminopenicillin resistance in Escherichia coli and methicillin resistance in Staphylococcus aureus.

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The researchers created a simplifying indicative index to show the difference in predicted resistance between two specific age groups: individuals aged 100 years and individuals aged 1 year.

Across Europe, the findings revealed distinct patterns in resistance prevalence by age. Trends often varied more within an antibiotic family, such as fluroquinolones, than within a bacterial species, such as Pseudomonas aeruginosa.

MSRA resistance increased with age in males aged between 1 and 100 years in 72% (n = 21) of countries, and a greater change in resistance was seen in males compared to females. For P. aeruginosa, a peak in resistance to several antibiotics occurs across both sexes at approximately 30 years of age.

A u-shaped pattern of infection incidence with age was seen for most bacterial species, with the young and old being more likely to get infections. The infection incidence was also higher in males than females, with one exception being E. coli, where an elevated incidence was measured in females between the ages of 15 and 40 years.

Aminopenicillin resistance in E. coli decreased across the entire age range from 1 to 100 in both males and females in 93% of the countries studied (n= 27), although the pattern of resistance change was slightly smaller in females.

Resistance rates were found to vary by 38% across a country. For MRSA the change in resistance prevalence between 1 and 100 years ranged up to 0.51 in one country. For aminopenicillin resistance in E. coli, the resistance prevalence varied between 0.16 and -0.27 across individual countries.

Dr Gwen Knight, associate professor and co-director of the Antimicrobial Resistance Centre at LSHTM, said: ‘Our findings highlight important gaps in our knowledge of the spread and selection of antimicrobial resistance and may help us understand why the epidemiology has been difficult to explain through known patterns of antibiotic exposure and healthcare contact.

‘They also suggest there may be value in considering interventions to reduce antimicrobial resistance burden that take into account important variations in antimicrobial resistance prevalence with age and sex.’

She added: ‘In order for us to address this growing threat to public health, we now need data from a wider range of sources to determine the contribution that cultural versus natural history differences have in driving these patterns globally and the role that they play in the increasing rates of antimicrobial resistance being seen.’

In 2023, a study revealed how mixed strain infections within the host play a key role in shaping the emergence of resistance in response to treatment.

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