The threat of antimicrobial resistance
Can the threat of superbugs be halted?
Antibiotics are a pillar of modern medicine, but antimicrobial resistance poses a worrying threat to human health. Reports have warned in apocalyptic language of a “public health catastrophe,” with millions of lives at risk.
In 2013, the chief medical officer for England, Sally Davies, declared antimicrobial resistance “as big a risk as terrorism” and chose the problem as the focus of her annual review. Prime minister David Cameron warned of being “cast back into the dark ages of medicine.” The subject has received attention from the World Health Organization, which last year published its first global antimicrobial resistance surveillance report.
Antimicrobial resistance was voted as the focus for the £10m (€14m; $15m) 2014 Longitude Prize, which was offered by the innovation charity Nesta and the government funded Technology Strategy Board to tackle a major scientific challenge.
In the face of uncertain diagnoses, doctors sometimes adopt an overcautious approach and prescribe broad spectrum antibiotics as first line treatment, which in turn unintentionally increases antimicrobial resistance. The Longitude Prize challenges innovators to develop cheap and rapid point of care test kits which detect bacterial infections that require antibiotics—rather than viral infections, for example—and which type of antibiotics are needed.
Davies paints a stark picture of the future if we don’t take urgent action: “Each year we see 5000 people dying in England from E coli [Escherichia coli] antibiotic resistant infections. If AMR [antimicrobial resistance] is not addressed, then many medical treatments and procedures that we consider as routine will not happen as we will not have the antibiotics needed to treat infections associated with them,” she told Student BMJ.
How have we reached a point where drug resistance is considered one of the greatest problems of our time? How can we safeguard our future and avoid the return of deadly infections?
What drives antimicrobial resistance?
The discovery of penicillin in 1928 heralded a new era of medicine, but from the outset there were concerns about the longevity of antibiotic use. The inherent capability of micro-organisms to rapidly alter their genetic make-up equips them well to evolve resistance mechanisms, leaving previously effective drugs futile. Any use of antibiotics inadvertently creates conditions that drive such change, by exposing microbes to selective pressure and allowing Darwinian survival of the fittest to take hold.
However, good clinical practice can minimise the risk of resistance emerging. Antibiotic misuse is often cited as a driver of antimicrobial resistance, but what does “misuse” mean?
Patients may not complete a course of antibiotics given for an infection. This may seem logical to the patient: if symptoms have cleared up there is no obvious incentive to continue taking the tablets. A “too short” course may kill off the most susceptible pathogens, leaving a hardened few that survive the sublethal exposure and develop defences for future. The purpose of taking drugs for a given duration is to make sure that the bacteria have fully cleared. It’s the duty of doctors to ensure patients understand this rationale; they cannot be expected to do simply as the doctor orders.
One would hope that doctors never intentionally misuse antibiotics, yet research by Public Health England warns that up to a half of the 6% increase in prescriptions between 2010 and 2013 may be “inappropriate.” Inappropriate use includes unnecessary prescriptions, unsuitable use of broad spectrum antibiotics, using the wrong antibiotics altogether, and inappropriate duration or dose. Drivers of unnecessary prescribing include patient expectations, together with lack of time to explain why an antibiotic is not appropriate, and a desire to avoid conflict.
Where are the new antibiotics?
Since the 1940s, when antibiotic development took off, we have enjoyed a golden age of antibiotics. However, the development of new antibiotics tailed off in the 1980s, leaving doctors with a limited range of effective antibiotics for diseases such as tuberculosis. One obvious solution to antimicrobial resistance is the development of new drugs.
Antimicrobials are not a priority for drug companies, which prefer to invest in more lucrative maintenance drugs for chronic disease. Davies acknowledged: “We need to find a way to incentivise pharma to reinvest in the research and development of antimicrobials. We have not had a new class of antibiotics since the late 1980s.”
Without good antimicrobial agents, the whole healthcare economy is at risk. Davies added: “If we do not have these [new antibiotic] drugs, then we will not be purchasing their other drugs, such as chemotherapy drugs, as the risk of infection will be such that it is not clinically relevant to run these treatments.”
Recent headlines suggest that all is not lost. Work on soil bacteria in the United States has yielded 25 new antibiotics to be investigated, in what scientists have described as “game changing” advances.
New drugs cannot be the whole answer, however. Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh, says: “I regard it a short term fix along the lines of the Red Queen’s line in Alice in Wonderland that you have to keep running as fast as you can to stay in the same place.”
So new drugs must be coupled with improved antimicrobial stewardship—the responsible use of resources that aims to maximise clinical outcomes. Good stewardship means careful use, optimising drug regimens, therapy duration, and route of administration.
Finally, we need to remember the lessons of pre-antibiotic medicine regarding infection control. Healthcare settings are epicentres of infection and represent the perfect breeding ground for antimicrobial resistance. Laura Piddock, professor of microbiology at Birmingham University, says: “[We need] infection prevention everywhere, not just in hospitals. This will minimise the risk of infection and hence the need to treat infections with antibiotics.”
Is it possible to achieve sustainable levels of effective antimicrobial use? Alongside new drugs and improved stewardship, Davies emphasises the need for cross sector, global collaboration.
The UK government acknowledged the importance of cooperation on a global scale by commissioning a major review, which will bring together a panel of international experts to examine all aspects of the issue and identify proposals for the fight against antimicrobial resistance.
An important component of antimicrobial resistance that is easily overlooked is the use of antimicrobials in agriculture. Livestock health is a priority for farmers, faced with small profit margins. Antibiotics are often used to reduce the risk of infection among herds. However, it is important not to overplay agriculture’s contribution to antimicrobial resistance in humans. Latest reports suggest that clinical problems with resistance in humans originate from antibiotic use in humans, rather than in animals.
Improving education for doctors and patients might help alleviate the public pressure on general practitioners and reduce the number of people who take and share antimicrobials inappropriately.
The onus is on us as the next generation of doctors to deal with the problem of antimicrobial resistance. We need to familiarise ourselves with the policies to help us prescribe appropriately, whether in hospital or general practice (see box). And we need to ensure the policies are put into practice.
A 2014 survey of NHS trusts found that although the prescribing toolkit “Start Smart, then Focus” was reviewed by most respondents, less than half had an action plan in place to improve responsible antibiotic use. Recent research has looked at making available point of care test kits and training in communication skills. Doctors reported that both interventions helped them to reduce unnecessary antibiotic prescriptions.
Sally Davies says that today’s medical students have a key part to play. “Medical students are the prescribers of the future and thus are critical to the fight against AMR [antimicrobial resistance]. You all have a role to ensure that antimicrobials are only used where clinically relevant, and help educate patients where needed,” she said. She suggested students visit the website http://antibioticguardian.com and sign up to become an Antibiotic Guardian. This means making a pledge to protect antibiotics in whatever capacity you can. The future might not be bright, but we have the responsibility and opportunity to stop it looking quite so bleak.
Advice on the responsible use of antibiotics
TARGET stands for Treat Antibiotics Responsibly, Guidance, Education, Tools. The TARGET antibiotics toolkit includes the following resources:
- Interactive workshop presentation
- Leaflets to share with patients
- Audit toolkits
- National antibiotic management guidance
- Training resources
- Resources for clinical and waiting areas
- Self assessment checklist
The Start Smart toolkit
- Do not start antibiotics in the absence of clinical evidence of bacterial infection
- If there is evidence or suspicion of bacterial infection, use local guidelines to initiate prompt effective antibiotic treatment
- Document on drug chart, and in medical notes, the clinical indication, duration or review date, route, and dose
- Obtain cultures before starting treatment
- Prescribe single dose antibiotics for surgical prophylaxis where antibiotics have been shown to be effective.
The Then Focus toolkit
- Review the clinical diagnosis and the continuing need for antibiotics by 48 hours and document a clear plan of action—the Antimicrobial Prescribing Decision—in medical notes
- The five antimicrobial prescribing decision options are stop, switch intravenous to oral, change, continue, and outpatient parenteral antibiotic therapy.
It is essential that the review and subsequent decision are clearly documented in the medical notes[(8)]
1University of Oxford, UK
Correspondence to: email@example.com
Competing interests: None declared.
Provenance and peer review: Not commissioned; not externally peer reviewed.
- Public Health England. New report shows stark effect of antibiotic resistance. 2014. www.gov.uk/government/news/new-report-shows-stark-effect-of-antibiotic-resistance.
- Walsh F. Antibiotics resistance “as big a risk as terrorism”—medical chief. BBC News, 2013. www.bbc.co.uk/news/health-21737844.
- Walsh F. Antibiotic resistance: Cameron warns of medical “dark ages.” BBC News, 2014. www.bbc.co.uk/news/health-28098838.
- World Health Organization. Antimicrobial resistance: global report on surveillance 2014. www.who.int/drugresistance/documents/surveillancereport/en/.
- Longitude Prize 2014. www.longitudeprize.org/challenge/antibiotics.
- Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR). Report 2014.www.gov.uk/government/uploads/system/uploads/attachment_data/file/362374/ESPAUR_Report_2014__3_.pdf.
- Gallagher J. Antibiotics: US discovery labelled “game-changer” for medicine. BBC News, 2015. www.bbc.co.uk/news/health-30657486.
- UK Government Department of Health: Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI). Antimicrobial stewardship. “Start smart—then focus.” Guidance for antimicrobial stewardship in hospitals (England). November 2011. www.gov.uk/government/uploads/system/uploads/attachment_data/file/215308/dh_131181.pdf.
- Wellcome Trust. Internationally focused commission on antimicrobial resistance announced by PM. Press release. 2014. www.wellcome.ac.uk/News/Media-office/Press-releases/2014/WTP056762.htm.
- Department of Health. UK Five Year Antimicrobial Resistance Strategy 2013 to 2018. 2013. www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018.
- Anthierens S, Tonkin-Crine S, Cals JW, et al. Clinicians’ views and experiences of interventions to enhance the quality of antibiotic prescribing for acute respiratory tract infection. General Journal of Internal Medicine 2014; http://eprints.soton.ac.uk/372678/.
- Royal College of General Practitioners. TARGET antibiotics toolkit. Retrieved 2014. www.rcgp.org.uk/targetantibiotics.
Cite this as: Student BMJ 2015;23:h1326