According to the World Health Organisation, antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by it. Resistant microorganisms (including bacteria, fungi, viruses and parasites) are able to withstand attack by antimicrobial drugs, so that standard treatments become ineffective and infections persist. Alternative medications or higher doses are therefore required – which may be more costly or more toxic – or treatment fails altogether. AMR is therefore a broader issue than bacterial antibiotic resistance alone, but the scope of this chapter is limited largely to the latter – as this is perhaps of greatest concern
The initial evolution of resistant microorganism strains is a natural phenomenon that occurs when they replicate themselves erroneously (a mutation) or when resistant traits are exchanged between them. The use/misuse of antimicrobial drugs then accelerates the emergence of drug-resistant strains.
The circles indicate individual bacteria. A yellow bacteria is very sensitive to Antibiotic X, meaning treatment will be successful. A red bacteria is more resistant to Antibiotic X, meaning they may only be sensitive at higher doses/to a longer course of treatment, or treatment may be unsuccessful.
Antibiotic misuse contributes to resistance in the following ways:
AMR is a rapidly growing public health threat for two reasons:
Essentially, the demand for new drugs has increased but the supply has dried up. Infections with resistant organisms now occur both in community and hospital populations. The World Health Organisation (WHO) estimates that antibiotics add 20 years to average life expectancy. Currently AMR is responsible for 700,000 deaths per year worldwide but by 2050, it could kill someone every three seconds. In a keynote address at a conference on Combating Antimicrobial Resistance, Dr Margaret Chan, Director-General of WHO stated:
“If current trends continue unabated, the future is easy to predict. Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry. The cupboard is nearly bare. A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill”
Though AMR occurs across many strains of bacteria and to a wide range of antibiotics, examples of more noteworthy AMR organisms in England include, but are not limited to:
It is well understood that a key part of the battle against AMR will be public perception and, to this end, research has been carried out world-wide exploring what is generally understood around the subject. The Wellcome Trust recently commissioned work to explore the British public’s relationship with antibiotics. This revealed:
The study also found that, even with nomenclature clarified, there were still vast misconceptions about appropriate antibiotic use – findings that were shared in a similar survey of the American general public. Many people felt validated when they were prescribed antibiotics, commenting, “It confirms I’m ill”, others thought of antibiotics as “a magic pill” to help them get better.
Perhaps more worryingly, this same Department of Health survey demonstrated even those with better understanding of AMR were just as likely to use antibiotics inappropriately. Though sometimes increased knowledge was associated with more prudent use (more likely to complete a course of antibiotics), sometimes it was associated with more irresponsible activity (more likely to self-medicate and to keep left-over antibiotics for future use).
Even when AMR is well understood, and antibiotics are used responsibly, the scale of the issue is seemingly missed. In the American study discussed, the vast majority agreed that inappropriate antibiotic use contributes to antibiotic resistance (92%), but most (70%) felt that AMR was not a major problem.
In 2016, the Department of Health updated their Antimicrobial Resistance Empirical and Statistical Evidence-Base. In this they discuss increasing antibiotic use and trends in AMR.
Increased use of antibiotics is the primary driver for the development of resistance. The standard measure of use (prescribing) is Defined Daily Dose (DDD) per 1000 population. The majority of antibiotic prescribing occurs in primary care, but in secondary care, broad-spectrum antibiotics (such as cephalosporin, quinolones and co-amoxiclav) are prescribed. Broad spectrum antibiotics are effective against a wide range of bacteria, but are more likely to drive resistance. As will be discussed in greater detail below, a key aim of the current UK Five Year Antimicrobial Resistance Strategy is the conservation and stewarding of currently available antibiotics – this means reducing the number of prescriptions, particularly the number of broad-spectrum prescriptions.
Figures 1 & 2 reflect the trends (2010 Quarter 1-2016 Quarter 1) in ‘Total number of prescribed antibiotic items per 1000 resident individuals by quarter’ for the two CCGs, while Figures 3 & 4 compare the 2016 Q1 data for the CCGs, to their Deprivation Decile and CCG cluster.
Figure 1: North & West Reading CCG – Total number of prescribed antibiotic items per 1000 resident individuals by quarter
Figure 2: South Reading CCG – Total number of prescribed antibiotic items per 1000 resident individuals by quarter
Figure 3: Figure 3: North & West Reading CCG – Total number of prescribed antibiotic items per 1000 resident individuals in 2016 Q1 – comparing CCG value, Deprivation Decile and CCG cluster
Figure 4: Figure 3: North & West Reading CCG – Total number of prescribed antibiotic items per 1000 resident individuals in 2016 Q1 – comparing CCG value, Deprivation Decile and CCG cluster
The above Figures show the rate of antibiotic drug consumption in the CCG by quarter by taking into account all prescribing at the primary care level. There is clear seasonal variation.
Figures 5 and 6 show the trends in ‘Percentage of prescribed antibiotic items from cephalosporin, quinolone and co-amoxiclav class by quarter’ for the two CCGs, while Figures 7 and 8 compare the 2016 Quarter 1 data for the CCGs, to their Deprivation Decile and CCG cluster.
Figure 5: North & West Reading CCG – Percentage of prescribed antibiotic items from cephalosporin, quinolone and co-amoxiclav class by quarter
Figure 6: South Reading CCG – Percentage of prescribed antibiotic items from cephalosporin, quinolone and co-amoxiclav class by quarter
Figure 7: North & West Reading CCG – Percentage of prescribed antibiotic items from cephalosporin, quinolone and co-amoxiclav class in 2016 Q1 – comparing CCG value, Deprivation Decile and CCG cluster data
Figure 8: South Reading CCG – Percentage of prescribed antibiotic items from cephalosporin, quinolone and co-amoxiclav class in 2016 Q1 – comparing CCG value, Deprivation Decile and CCG cluster data
This indicator specifically shows the percentage of broad spectrum items that are being prescribed by quarter. There is a clear trend of proportionally reduced consumption of these drugs in both CCGs. Further, both CCGs see proportionally fewer prescriptions of these drugs than its comparative areas – suggesting appropriate antimicrobial stewardship.
The aim of antimicrobial stewardship is to reduce the proportion of bacteria that are resistant to treatment. Data on resistance and trends is most frequently obtained from surveillance systems though, and there are a number of limitations to this approach:
No local information is available, but the 2015 ESPAUR report and also the annual progress report of the UKs current AMR strategy reviewed the national incidence of infection and the proportion of resistance.
The ESPAUR report found that from 2010 to 2014:
The incidence of
The Department of Health update showed that between 2013 and 2014:
The importance of AMR has been recognised now for many years. In an interview shortly after winning the Nobel Prize in 1945 for discovering Penicillin, Alexander Fleming said:
“The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism”
The first World Health Assembly AMR resolution was agreed in 1998 and the need to accelerate progress has been acknowledged by both the WHO and European Commission. The first UK AMR Strategy was published in 2000 and the most recent update was a five year strategy released in 2013.
This represented an ambitious programme to slow the development and spread of AMR and rested on the three pillars of prevent, protect and promote: preventing infection, protecting the antibiotics that we have (stewardship) and promoting the development of new drugs and alternative treatments. Examples of actions currently taken to Tackle AMR in the UK are:
These measures are underpinned by authoritative, evidence based guidance developed by NICE and also appear in the Quality and Outcomes Framework (QOF) and supported by the 3 CCGs of Berkshire East (Bracknell & Ascot, Windsor and Maidenhead, Slough) in their Operational Plan 2016/17 and by the 4 CCGs of Berkshire West (Wokingham, Newbury and District, South Reading and North and West Reading) in theirs. These include:
In 2015, all 7 CCGs agreed to prescribing guidelines for use in primary care:
The UK Five Year Antimicrobial Resistance Strategy (2013 to 2018) lists 7 key areas for future action:
Early in 2016, Lord O’Neill, who led a government review on AMR, called for a £1.5 billion investment in global innovation funding for research by 2020. On 21st September 2016, the United Nations held a High Level Meeting On Antimicrobial Resistance to “summon and maintain strong national, regional and international political commitment in addressing antimicrobial resistance comprehensively and multi-sectorally, and to increase and improve awareness of antimicrobial resistance.” The signatories now have two years to report back with an action plan.
AMR is a vitally important yet poorly understood issue that requires urgent focus at local and national level. We can’t stop bugs becoming resistant to antibiotics, but we can slow the process down. Though certain patient populations, prescribing practices and environments may contribute to resistance more than others, AMR does not then discriminate – it will affect everyone – and everyone has a part to play.
Recently, a Berkshire-wide AMR stewardship group with representatives from all the main trusts in primary and secondary care has been established. The aim of the group is to concentrate and amalgamate efforts to comply with the strategies listed above. As well as working to improve awareness and understanding of AMR, a good example of this is the Antibiotic Guardian campaign.
Antibiotic Guardian is a PHE-led drive to encourage improved behaviours and engagement on the prudent use and prescription of antibiotics with members of the public and healthcare professionals. Antibiotic Guardians sign up online, and in doing so choose one pledge about how they can personally prevent infections, or make better use of antibiotics. You can be a healthcare professional, a student or educator, or a member of the general public and though PHE were aiming to reach 100,000 Antibiotic Guardians by March 2016, at time of writing, the current pledge count was 32,975.
Public Health England has local data available regarding ‘Antibiotic Guardians per 100,000 population per year’ as a measure of engagement within the area on antibiotic resistance. Antibiotic Guardians submit half-postcodes during their signup, which are then matched to their CCG catchment area by calendar year.
For the Reading Local Authority (including parts of North and West Reading and South Reading CCGs), Figures 9/10 and 11/12 show the level of engagement with this programme. Using data from the aforementioned PHE profiles, Figures 9/10 show the amount of antibiotic guardians in 2013 and 2014, while Figures 11/12 compare this data to the appropriate deprivation decile and CCG cluster grouping.
Figure 9: North & West Reading CCG – Antibiotic Guardians per 100,000 population per calendar year by CCGs
Figure 10: South Reading CCG – Antibiotic Guardians per 100,000 population per calendar year by CCGs
Figure 11: North & West Reading CCG – Antibiotic Guardians per 100,000 population per calendar year by CCGs – comparing CCG value, Deprivation Decile and CCG cluster data
Figure 12: South Reading CCG – Antibiotic Guardians per 100,000 population per calendar year by CCGs – comparing CCG value, Deprivation Decile and CCG cluster data
Unfortunately the number of Antibiotic Guardians dropped from 2014-15 for both CCGs. North and West Reading CCG compares poorly to other similar areas (CCG cluster and Deprivation Decile). Though Antibiotic Guardians dropped from 2014-15 in South Reading CCG, it actually compares well to other similar areas (CCG cluster and Deprivation Decile).
As stated, AMR does not discriminate. Many factors have and will contribute to its impact, but it will impact everyone. It is impossible to predict the path of emerging drug resistance, but it is a trend that has largely run only in one direction so far. What we can be certain of is that, in the absence of interventions to slow the emergence of resistance, the impacts will be felt not just in isolated areas but at a far more fundamental level, across our societies and healthcare systems.
Though antibiotics are primarily used to treat infection, they also play a key role prophylactically in reducing life threatening complications in surgery, chemotherapy and transplantation. In the past, resistant infections were associated predominantly with hospitals and care settings, but over the last decade resistant infections have been seen in the wider community too.
Though certain patient populations may thus be affected by AMR earlier than others (e.g. elderly populations or chronic disease groups), even everyday infections that we now seen as trivial may once again soon be deadly.
Before the availability antimicrobials there was greater inequality in health. Will the restriction of antimicrobials, and the rise of AMR, mean a return to greater health inequalities?
In May 2015, the Sixty-eight World Health Assembly adopted the global action plan on antimicrobial resistance. Within this are the Global Strategy Recommendations. Although the full list is available here – and contains advice for national governments and health systems – recommendations appropriate to the UK and Reading include:
Prescribers and Dispensers
PHE centres should ensure that the ESPAUR report is discussed at meetings, local Quality Surveillance Groups, strategic clinical networks, health protection committees, local infection prevention and control committees.