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26th March 2024
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.
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.
18th July 2023
The assumption that pathogen populations within a host are clonal and therefore antimicrobial resistance (AMR) will occur through the emergence of de novo variants has been challenged by a new study offering insight into the mechanism through which AMR is generated.
Published in the journal Nature Communications, the study showed how mixed strain infections within the host play a key role in shaping the emergence of resistance in response to treatment.
Using Pseudomonas aeruginosa – an opportunistic pathogen that is an important cause of hospital-acquired infection – as an example, they studied changes in the genetic diversity and antibiotic resistance of Pseudomonas aeruginosa collected from lower respiratory tract samples from intensive care unit (ICU) patients before and after antibiotic treatment.
The patients were part of the ASPIRE-ICU observational trial of Pseudomonas infection across European hospitals. They were screened for Pseudomonas soon after admission to ICU and at regular intervals thereafter.
Pseudomonas isolates were sampled in an unbiased manner – without a consideration of resistance phenotypes – and up to 12 randomly chosen isolates were collected from all patient samples containing Pseudomonas. These samples were analysed using a combination of phenotypic assays, looking at resistant organisms and genomic analyses to quantify within-patient diversity and antibiotic resistance.
In total, 441 isolates were collected to characterise the diversity of Pseudomonas aeruginosa using lower respiratory tract samples from 35 ICU patients in 12 different hospitals.
The researchers found that while 23 of the 35 patients were colonised with a single strain, roughly a third (12 patients) displayed multiple strains and this strain diversity tended to be high.
Antimicrobial resistance evolved rapidly in patients colonised by diverse Pseudomonas aeruginosa populations, and this occurred through selection of pre-existing resistant strains, showing a clear link between within-host diversity and resistance.
The researchers suggested that this underscored the importance of within-host bacterial diversity as a means for understanding antimicrobial resistance.
They also felt that in future, measuring the diversity of pathogen populations could make it possible to more accurately predict the likelihood of treatment failure for individual patients.
28th April 2023
Antimicrobial resistance is one of the biggest challenges for hospitals and healthcare services to deliver safe and effective healthcare. A 2018 survey estimated that around 33,000 people die each year in the in the European Union and European Economic Area as a direct consequence of an infection due to bacteria resistant to antibiotics.
In 2020, the European Hospital and Healthcare Federation (HOPE) published a position paper on antimicrobial resistance (AMR). Here, the organisation’s chief executive Pascal Garel provides an update and offers his recommendations on prevention policies, fostering the One Health Approach and promoting the development of new antimicrobials.
The ‘One Health’ perspective of the European Commission’s Action Plan provides an opportunity for stakeholders representing different sectors and constituencies to provide expert inputs for improving the implementation of the Plan. This includes experts from the human health, animal health and food production, and environmental disciplines.
Hospital and healthcare providers are clearly important in this regard. Healthcare environments are places where antimicrobial-resistant bacteria emerge and spread, but also where actions can be particularly effective for preventing future outbreaks and ensuring prudent use of antimicrobials.
Other important voices involved in fighting antimicrobial resistance are: medical professionals, nurses, hospital and community pharmacists, students, infection prevention and control specialists and carers. In addition, it is relevant to include organisations with a broader remit, such as public health, health education and research-focused organisations, and those promoting solutions such as rapid diagnostics, vaccines and alternative medicines for veterinary uses.
It is not sufficient to rely exclusively on Member States’ own funding, given that there is a marked north-south and west-east gradient regarding consumption of antimicrobials and AMR prevalence. Moreover, the development and implementation of National Action Plans (NAPs) has been uneven. Over half of the Member States have no action plans, or have plans that are no longer valid or about to expire. A lack of access to funding – including the possibility to combine different funding programmes and projects to complement one another in the longer term – and of other resources, such as laboratory capacities, healthcare resources, infection prevention and control specialists, are often cited as main reasons.
Supplementing national budgets with a dedicated EU-AMR funding mechanism is necessary to close these gaps. Using the European Structural and Investment Funds and providing technical assistance through the European Structural Reform Support Programme is also needed.
The impact of Covid-19 on healthcare budgets and on the ability of hospitals and healthcare facilities to operate effectively should not be underestimated. Health worker shortages, supply issues related to PPE, and persistent budget cuts are stretching many health institutions to the limit. While it is clear that the size and immediacy of the AMR threat will necessitate the diversion of some national and institutional funds, this is not sufficient to solve the issue and could indeed exert a negative impact on other crucial areas, such as the ability to guarantee continuity of care during health security crises.
A key barrier is the need to develop, adopt and fund a long-term vision that exceeds the political mandates of most national governments and hence complicates endorsement and implementation of NAPs. Therefore, the role of the European Commission and of international groups – such as the WHO, G7 and G20 – is vital in avoiding AMR slipping off the political radar and any policies under development merely following a one-sided approach.
More tangible guidance on devising impactful antimicrobial resistance frameworks is required. This goes beyond listing actions to include dedicated funding pooled from different policy areas. Increased political instability and societal divisions – reared also by ‘fake news’ and conspiracy theories online – further complicate this task as decision-makers are primarily focused on short-term quick wins.
The pandemic crisis demonstrated that action can be taken quickly when needed: the problem being that the new EU health budget is the product of a reactive rather than proactive approach. However, the AMR threat is as serious as that of Covid-19, and concrete steps are required to move towards a European Health Union. These steps are driven by values of solidarity, with the European Centre for Disease Prevention and Control given an enhanced health security framework and extended powers for surveillance, preparedness and response planning.
There is growing awareness at national level that certain health-related problems – such as AMR – require enduring and targeted commitment as well as dedicated financial, human and technological resources. The EU One Health Network should be replicated at national level in recognition of the urgency.
We work in partnership with stakeholders representing the agricultural and veterinary areas as part of an AMR Stakeholder Network originally created under the European Health Policy Platform. The One Health perspective draws attention to the interlinkages between excessive uses of antibiotics in food production, animal husbandry and human health, among other things contributing to the rise of non-communicable chronic diseases and the growing threat of infectious diseases and pandemics, both, in turn, requiring functional antibiotic drugs to combat them.
Without being able to speak for the agricultural and veterinary sector, HOPE endorsed the AMR Stakeholder Network’s Roadmap. EU rules banning the routine use of antibiotics and restricting preventative uses to special circumstances are in place. However, the bigger change needed is moving away from highly intensive livestock farming systems involving both routine and excessive use of antibiotics. Available options include altering production systems by reducing stocking density, different breeds and so on; exploring alternatives to antibiotics; and antibiotic stewardship programmes.
Establishing an EU-wide antibiotic formulary is not feasible given the different healthcare needs, patient profiles and antimicrobial prescribing practices at national and regional levels. However, the existing EU Guidelines for the prudent use of antimicrobials in human health should be expanded. This could include more concrete information aimed at different professions. Some harmonised guidance for specific antimicrobials commonly used in all countries could contribute to better prescribing and handling in all Member States.
Member States developing stewardship programmes within the hospital sector, but also covering community and long-term care settings, with the help of EU funding ensures that healthcare professionals are well prepared to tackle multi-drug resistance. This would also facilitate cross-border cooperation and better ensure that AMR protocols are adhered to during serious health crises such as the Covid-19 pandemic.
A multidisciplinary approach to the implementation of stewardship programmes encourages mutual learning and transfer of expertise. This is more effective than offering lectures or encouraging self-study.
Antimicrobial stewardship should be part of educational curricula to inform students and trainees of antimicrobial resistance and encourage prudent use from the outset.
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