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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 Over half of the Member States have no action plans, or have plans that are no longer valid or about to expire.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.
3rd March 2023
The introduction of an antimicrobial stewardship intervention to older adult care facilities, significantly reduced the level of antibiotic prescribing for frail older adults with a suspected urinary tract infection according to the findings of a cluster, randomised trial by European researchers.
Antimicrobial resistance poses a global, major threat to human health and is recognised as a leading cause of deaths around the world. Older and frail adults are often prescribed antibiotics for a urinary tract infection (UTI) and often in the presence of non-specific symptoms such as confusion. Moreover, the presence of asymptomatic bacteriuria is a common finding which has become recognised as an important contributor to inappropriate antimicrobial use that ultimately promotes emergence of antimicrobial resistance. To date antibiotic stewardship interventions in long-term care facilities suggest that such programs collectively suggest potential to reduce antimicrobial use though the available interventions vary considerably with respect to design and intensity.
In the current study, researchers made use of a multifaceted antibiotic stewardship intervention that included a decision tool for appropriate use of antibiotics for a UTI and which was previously developed by an international expert team. The researchers wanted to find out if the intervention was effective in reducing antibiotic prescribing for suspected urinary tract infections in various older adult care settings, in comparison to usual care, in several European countries. The team used a pragmatic, parallel, cluster randomised controlled trial, with a 5 month baseline data collection period and a 7 month follow-up. They set the primary outcome as the number of antibiotic prescriptions for a suspected UTI per person-year, whereas secondary outcomes focused on the level of complications, hospital admissions and all-cause mortality.
Antimicrobial stewardship and treatment of suspected urinary tract infections
A total of 1,041 participants with a mean age of 86.3 years (70.9% female) were included and of whom, 502 were randomised to the antibiotic stewardship intervention.
During the baseline period, there was no difference in the level of antibiotic prescribing for a suspected UTI in the two groups (0.50 per person year vs 0.44 per person year, intervention vs usual care). However, during the follow-up period, the corresponding rates were 0.27 per person-year (intervention ) and 0.58 per person-year (usual care). This equated to an adjusted rate ratio of 0.42 (95% CI 0.26 – 0.68, p < 0.001).
Furthermore, there were no differences between groups with respect to either complications, hospital admissions or all-cause mortality.
The authors concluded that their antimicrobial stewardship intervention safely reduced antibiotic prescribing for a suspected UTI in frail older adults.
Citation
Hartman EAR et al. Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries. BMJ 2023
2nd February 2022
Pharmacist-led antimicrobial stewardship with emergency departments is associated with more appropriate antibiotic prescribing in adults who present with a range of infectious conditions. This was the conclusion of a systematic review and meta-analysis by a team from the Department of Pharmacy and the Department of Emergency Medicine, Mayo Clinic, Minnesota, US.
Research from the US suggests that an estimated 30% of outpatient, oral antibiotic prescriptions may have been inappropriate, highlighting a need for effective antimicrobial stewardship programs within an emergency departments.
However, one systematic review addressing this topic concluded that while such interventions may improve patient care, the optimal combination of interventions is unclear. While the review did not consider pharmacist-led interventions, other reviews have demonstrated that within an inpatient setting, pharmacist-led educational antimicrobial stewardship interventions are effective at increasing guideline compliance and reducing duration of antimicrobial therapy.
Although prior research has demonstrated that a clinical pharmacist within an emergency department is of value, the impact of a pharmacist-led antimicrobial stewardship program within emergency departments remains unknown.
For the present study, the US team set their primary aim as an assessment of the impact of pharmacist-led antimicrobial stewardship interventions, on the appropriateness of antibiotic prescribing within emergency care settings. The secondary aim was to assess the impact of any such interventions on time to culture review, time to appropriate antibiotics and emergency care return rates.
Findings
The literature review identified 22 studies including 5,062 patients that were suitable for analysis, the majority of which were retrospective observational cohorts, including before and after assessments though there were no randomised, controlled trials.
The nature of the studies varied and interventions included pharmacist-led culture reviews, the presence of a pharmacist in the department, pharmacist directed clinical algorithms, clinician education and one prospective antibiotic review.
In an assessment of appropriate versus inappropriate antibiotics, the pooled odds ratio (OR) was 3.47 (95% CI 2.39 – 5.03) when chosen by a pharmacist during the intervention. For specific conditions, appropriate antibiotic selection was more appropriate with pharmacist involvement for pneumonia (OR = 3.74) and urinary tract infections (OR = 1.76).
In subgroup analysis, the presence of a pharmacist led to improvements in each of the areas examined. For example, pharmacist presence within the department for antibiotic selection was better than no pharmacist for appropriate antibiotic selection (OR = 3.13), culture review (OR = 2.22) and pharmacist directed algorithms and clinical education (OR = 5.23).
However, the time to culture review and time to patient contact were no different with or without a pharmacists, although the time to appropriate antibiotic was significantly shorter in the presence of a pharmacist (mean difference 18.86 hours).
The authors concluded that the presence of a pharmacist or pharmacist-led antimicrobial stewardship interventions appeared effective for ensuring appropriate prescribing of antibiotics in adult patients presenting to emergency departments despite how the majority of included studies had a moderate risk of bias.
Citation
Kooda K et al. Impact of Pharmacist-Led Antimicrobial Stewardship on Appropriate Antibiotic Prescribing in the Emergency Department: A Systematic Review and Meta-Analysis Ann Emerg Med 2022.
24th August 2018
Kathy Oxtoby looks at the effects of antimicrobial resistance across Europe will be if it goes unchecked and investigates what should be done to tackle it.
It may be a natural phenomenon, but antimicrobial resistance (AMR) has become a global health crisis of similar importance to infectious-disease pandemics, according to the World Health Organization (WHO).
Increasing development and use of antibiotics during the second half of the 20th century has led to bacteria becoming resistant to new antibiotics within months or years of them entering clinical practice.
During the last 15 years, resistance has become a serious issue – largely driven by overuse of antibiotics. New resistance mechanisms have evolved, including the ability for resistance genes to be shared amongst species of bacteria.
“Antibiotics were seen as a cure-all. And although we knew about AMR, we didn’t realise how serious an issue this would become if we didn’t use antibiotics carefully,” says Dr Jacqueline Sneddon, project lead for Scottish Antimicrobial Prescribing Group and chair of Royal Pharmaceutical Society (RPS) Antimicrobial Expert Advisory Group.
So what is the extent of antimicrobial resistance, what are its effects and – crucially – is there still time to halt its rapid spread?
The EU started to take action around AMR in the late 1990s and made its first recommendations to tackle it in 2001. Antibiotic use is the key driver of AMR, so countries where there are higher levels of antibiotic use have higher levels of resistance. In Europe, countries in the south have higher levels of resistance compared to northern Europe, where Scandinavia has the lowest levels.
“The reasons [for AMR variance] are complex but are often based around antimicrobial consumption and infection, prevention and control practices,” says Philip Howard, president of the British Society for Antimicrobial Chemotherapy.
AMR in the UK has been stable for several years, “which is the best case scenario”, given that it cannot be eliminated, says Ms Sneddon. There are some minor differences in resistance rates between the four UK nations and all countries have seen small year on year increases in multi-drug resistant gram negative bacteria.
While AMR rates remain stable in the UK, its consequences can be fatal. According to Public Health England (PHE) it is estimated that at least 5,000 deaths are caused every year in England because antibiotics no longer work for some infections in certain patients.
The English Surveillance Programme for Antimicrobial Utilisation and Resistance’s latest ESPAUR report –published in 2017 – reveals that in England, four in 10 patients with an E.coli bloodstream infection cannot be treated with the most commonly used antibiotic (co-amoxiclav) in hospitals. In addition, almost one in five of these bacteria were resistant to at least one of five other key antibiotics.
The report also showed hospital prescribing has increased year on year, but use of the last resort antibiotics (piperacillin/tazobactam and carbapenems) has reduced by 4% between 2015 and 2016.
But there are fears that in the future the issue of AMR could reach crisis point where antibiotics no longer work, propelling medicine back to the dark ages. Some countries in the world, such as Greece, are already reported to be at crisis point, with hospitals trying to treat patients with infections that are resistant to last line antibiotics.
In the UK, there have been alarming predictions about the situation in 2050 if action is not taken. Lord O’Neill in his review on AMR suggested there could be 10 million deaths per year worldwide.
However, Mr Howard says the current PHE guidance in place to screen patients admitted from overseas hospitals or hospitals with known carbapenemase-producing Enterobacteriaceae (CPE) problems “appears to be working well”.
“The increasing numbers of CPEs are from colonisation identified through screening rather than clinical infections. Hopefully, the current UK drivers to reduce the proportion of broad spectrum and total antibiotics through minimising inappropriate antibiotic prescribing linked to effective infection prevention and control measures will keep the crisis point a long way off,” he says.
However, the future looks bleak if action is not taken. If antimicrobial resistance across Europe goes unchecked, “more people will die from untreatable infections because of a lack of effective antibiotics”, he warns.
For example, the European Centre for Disease Prevention and Control (ECDC) has highlighted this concern in its country level report for Italy published in December 2017, which warns: “If the current trends of carbapenem resistance and colistin resistance in gram-negative bacteria such as Klebsiella pneumoniae and A. baumannii are not reversed, key medical interventions will be compromised in the near future. Untreatable infections following organ transplantation, intensive care or major surgical interventions are now a significant possibility in many Italian hospitals.”
Ms Sneddon says there is a “robust surveillance system in Europe” with countries submitting data on antimicrobial use and resistance to the European Centre for Disease Prevention and Control (ECDC).
The World Health Assembly has encouraged all member states to produce a national action plan (NAP) for AMR. All European countries have a NAP published or in progress.
There is also a European Commission One Health AMR Action Plan form, which was issued in 2017. This action plan is designed to support the EU and its member states in delivering, “innovative, effective and sustainable responses to AMR”, the commission says.
The fight against AMR is a priority for the European Medicines Agency (EMA) and the European Commission (EC).The EMA says it plays, “a vital role in the global fight against AMR” by supporting the development of new medicines and treatment approaches. The agency says it also promotes “responsible use of existing antibiotics” and collects “antimicrobial consumption data to guide policy and research”.
The UK Government has a five-year strategy to tackle AMR (2013-2018), which is shortly due to be updated. PHE says the strategy’s three main aims are to “improve the knowledge and understanding of antimicrobial resistance, conserve and steward the effectiveness of existing treatments, and stimulate the development of new antibiotics, diagnostics and novel therapies”.
Two key goals from PHE CC include reducing inappropriate antibiotic prescribing by 50% by 2021 and reducing gram-negative bloodstream infections by 50% by 2021.
To help guide prescribing in hospitals, PHE has developed the ‘Start Smart then Focus’ toolkit, which provides an outline of evidence-based antimicrobial stewardship in the secondary healthcare setting.
Everyone has a responsibility to tackle AMR, the health body believes. “Without action from all of us, common infections, minor injuries and routine operations will become much riskier,” PHE says.
Mr Howard says hospital pharmacists are central to an effective antimicrobial stewardship (AMS) programme “as they dispense the antibiotics and can control inappropriate use as well as provide antimicrobial consumption data at a very minimum”.
“They are integral to manage shortages of antibiotics. With appropriate investment and training, hospital pharmacy teams can play a key role in AMS programmes,” he says.
Hospital pharmacy’s involvement varies considerably dependant on the availability of hospital pharmacists by country and individual institution. The last global survey on AMS in hospitals from 2012 showed that, on average, there were 18 hours of antimicrobial pharmacy time per week in European hospitals. However, there was great variation from leading the hospital AMS programme to no involvement at all.
Hospital pharmacists are well placed to monitor use of antibiotics, to promote use of local guidelines and educate medical and nursing staff, Ms Sneddon believes. Over the last 15 years, antimicrobial pharmacy has evolved as a new specialism within hospital pharmacy.
“These pharmacists have a specific role in delivering antimicrobial stewardship and providing leadership for the pharmacy team in this area,” she says. And in the UK, all hospitals will now have an antimicrobial pharmacist working as part of a multi-professional antimicrobial team or committee.
Whether they work in clinical/ward roles or are based within the pharmacy department Ms Sneddon says all hospital pharmacists have a role to play in tackling AMR. “Those on the wards can screen prescriptions for antimicrobials to ensure that patients are receiving the correct treatment following local guidelines, can prompt review of intravenous antibiotics for switching to oral, can advise on therapeutic drug monitoring of aminoglycosides and glycopeptides and can educate ward staff about appropriate antibiotic use.
Pharmacists within the pharmacy department who check prescriptions or oversee supply of antibiotics should be familiar with local guidelines and query any use of non-guideline antibiotics, she says.
While many measures are in place to tackle AMR, and hospital pharmacists are clearly well placed to make a difference, is the situation improving?
Based on the latest ECDC report, Gram negative AMR is still growing but Gram positive has decreased. However, there is wide variation at a country level. For antimicrobial consumption, use within in the community has remained the same, but hospital usage has grown, and worryingly no country showed a significant reduction in carbapenems. Like AMR, there is wide variation at a country level on antibiotic consumption.
In the UK, antimicrobial stewardship programmes have been successful in improving the use of antibiotics “by reducing use of broad spectrum antibiotics, increasing compliance with local policies and education staff on appropriate use of antibiotics”, says Ms Sneddon.
But more must be done on a global scale to address AMR she believes. “A global effort is required because antibiotic use in one area of the world can affect us all due to the high level of air travel which can spread resistant bacteria.”
She says action is required at all levels from Government policymakers to healthcare providers and individual clinicians. Protection of critical antibiotics through restrictive policies that are effectively implemented and research to develop new antibiotics “are crucial”, she believes.
And there are “many examples of good practice in use of antibiotics in Europe, USA, South Africa and Australia and we need to learn from others what has worked to inform our own practice”, she adds.
Mr Howard would like to see a formal network of European hospital antimicrobial pharmacists to allow support at a local and national level. He says the more developed countries can support those still developing their AMS programmes.
He explains the AMS (ESGAP) group within ESCMID is developing a network for pharmacists and pharmacologist members. The European Association of Hospital Pharmacists has run some workshops so far, and there have been informal country visits.
In addition, BSAC is an antibiotic charity that provides free six-week course on antimicrobial stewardship in multiple languages, as well as a free electronic book on AMS, “both of which will be useful for European hospital pharmacists”, he says.
But unless the growing tide of Gram negative AMR can be stemmed, higher mortality rates from untreatable infections are inevitable, he warns.
With this threat ever present, Ms Sneddon says, “all pharmacists should be doing something to address AMR, regardless of which country they live in”.
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