Antimicrobial resistance and healthcare resilience: a game changer for the 21st century?

Antimicrobial resistance (AMR) - the resistance of microorganisms including bacteria and viruses to medicines that have previously been used to treat them - is a growing concern not only for the healthcare sector[1] but, increasingly, for security and resilience. Pandemic Influenza is comparable only to 'Catastrophic terrorist attacks' at the top of the UK's National Risk Register [2] with 'Other infectious diseases' and 'Zoonotic animal diseases' also featuring significantly highly. Serious outbreaks of such diseases may well result from the emergence of a strain that cannot be treated effectively with currently available drugs, or from one that quickly develops resistance to the stockpiled countermeasures.

AMR already places a significant burden on international governments, both in terms of patient morbidity and financial cost, and tackling it requires changes to thinking across a number of UK Government departments including the Home Office, Foreign and Commonwealth Office and Health Protection Agency as well as the Department of Health. More than 450,000 new cases of multidrug-resistant tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDRTB) emerge worldwide each year and cause approximately 150,000 deaths. Resistance to previously effective anti-malarial drugs such as chloroquine is growing in most malaria-endemic countries. A high percentage of Hospital Acquired Infections (HAIs), which leads to 37,000 deaths in the EU each year (a number comparable with the numbers that die in road traffic accidents)[3], are caused by bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In recent years, new drug-resistant strains of E.coli, Salmonella, Streptococci (responsible for pneumonia) and gonorrhoea have emerged.

In particular, AMR impacts on immigration policy. Despite tuberculosis (TB) being declared a global health emergency by the World Health Organization (WHO) in 1993, combating it remains a challenge. XDR-TB was first defined in 2006 and by 2010,[4] fifty-eight countries had reported at least one case. In some areas of the world, more than a quarter of all people newly diagnosed with TB no longer respond to standard treatment regimes. In the UK, more than 8 per cent of cases are now resistant to first line drugs, an increase of 25 per cent on 2010 and six of the twenty-four Extensively Drug Resistant (XDR) cases reported in the UK since 1995 occurred in 2011.[5] Rates of new TB cases increased year-on-year in the UK from a low of 5,000 per year during the 1980s to 7,167 in 2004 and though they have stabilised since 2005 they still remain high, with three-quarters of MDR-TB cases recorded in people born overseas, mainly in Sub-Saharan Africa and Asia.[6] This has implications not only for immigration policy but also for the movement of travellers to and from areas of the world where rates of TB are particularly high.

In 2011, the UK Border Agency led a review of border screening policy with the support of the Department of Health and the Health Protection Agency, to assess the efficacy of current UK immigration screening. This enabled comparison of different screening programmes in use by the UK and other nations, and an evaluation of pilot pre-entry models used in the UK since 2005; similar pre-entry models are used by the US, Australia and Canada. In May 2012,[7] Minister of State Immigration, Damian Green announced that the current process of screening migrants from high-incidence countries on arrival at UK airports should be phased out in favour of increasing pre-entry in-country screening, which currently takes place in 15 countries, to a further 67.[8]

International Co-operation

Increasing concerns over AMR are driving international co-operation and national initiatives. In 2011, the WHO World Health Day was dedicated to the issue. Other examples include the review of Hospital Acquired Infections and Antimicrobial Use across seventeen EU countries by the European Centre for Disease Control (ECDC) in 2008,[9] which aims to standardise the way data is collected so that it can be more easily analysed.  The US National Institute of Allergy and Infectious Diseases, National Institutes of Health [10] teamed up with the European Centre for Disease Control to form the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR), which published its first major report, Recommendations for future collaboration between the US and EU, in 2011.[11] The purpose of the taskforce is to intensify co-operation in three key areas it has identified: appropriate therapeutic use of antimicrobial drugs in the medical and veterinary communities; prevention of both healthcare and community associated drug-resistant infections; and strategies for improving the supply of new antimicrobial drugs.

Of the three key areas identified by the TATFAR report, the hardest to implement may well be addressing the 'appropriate therapeutic use' of microbial drugs. Over the last seventy years, the efficacy, ready availability and relatively low cost of antimicrobials has led to their considerable overuse. According to TATFAR, nearly 50 per cent of all antimicrobial use in hospitals is unnecessary or inappropriate, and 'the extensive use of antimicrobials has resulted in drug resistance that threatens', in the words of the report, 'to reverse the tremendous life-saving power of these drugs'.

Ironically, it is this therapeutic efficacy of antimcirobials that has led to the current levels of overuse. Antibiotics in particular ensure that diseases which were major killers in the past - such as tuberculosis and pneumonia - are easily survivable today. They make surgery much safer, significantly reduce  the risks associated with medical procedures that seriously compromise patients' immune systems, such as chemotherapy and organ transplants, and can prevent the spread of diseases such as pertussis (whooping cough) by limiting the period of infectiousness. AMR is a natural progression of evolution: when pressure is put on living organisms, they adapt to survive. Community Associated MRSA (CA-MSRA), a version of MRSA found increasingly in non-hospital settings has used another standard evolutionary practice - migrating to less hostile environments - in order to survive and thrive as healthcare facilities increasingly target its spread. The more antimicrobials are used, the faster the microorganisms they target will evolve into new resistant strains.

Understanding Risk Factors for Infection

Changing the way these drugs are used, and particularly changing the attitudes that lead to inappropriate overuse, is key to tackling AMR. However this is dependent on determining not only what constitutes appropriate use, but also on understanding how and why what might have been considered appropriate use in the past is no longer so today. Before AMR was so widespread, antibiotics could be freely administered on very low risk thresholds. As the risks associated with using them increase, so too do the risk thresholds need to adapt.

On 22 August, the UK's National Institute for Health and Clinical Excellence (NICE) published a new clinical guideline on the appropriate use of antibiotics. [12] It specifically discusses antibiotics in neonatal care, where risk thresholds are particularly low. To quote the consultation document for the review,[13]

'About 10 per cent of all newborn babies are investigated for possible early-onset infection and are treated with antibiotics. However, fewer than 5 percent of these treated babies are subsequently proven to have had an infection ... Stopping unnecessary antibiotics as soon as possible will help reduce the emergence of resistant bacterial strains'.

In order to facilitate this, the guideline takes an intelligent approach to risk, identifying thirty-one conditions that are currently considered to be possible signs of infection -  and thus likely to trigger antibiotic administration - and breaking them down into two groups of 'risk factors and clinical indictors'. Two of the eight risk factors, and four of the twenty-three clinical indicators are labelled as 'red flags', with the guideline recommending that, 'in babies with any red flags ... perform investigations and start antibiotic treatment', while, 'in babies without red flags and only one risk factor or one clinical indicator, using clinical judgement consider ... whether it is safe to withhold antibiotics.'

Reassessing risk in this manner will not only tackle AMR but also has significant financial benefits: decreasing the 95 per cent overuse of antibiotics in neonatal care to even the 50 per cent across hospitals in general identified as a problem by TATFAR could potentially save the NHS more than £80 million a year.[14] The methodology used could equally be applied to many other areas of medical practice, with comparable financial benefits. The WHO estimates that the worldwide economic burden from AMR is €1.5 billion a year, while TATFAR estimates the annual costs to the US healthcare sector to be $21-34 million.

Promoting Rapid Diagnostic Techniques

Withholding antibiotics from a patient in whom even just one risk factor has been identified is not completely without its dangers however and at least in the short term medical staff may be reluctant to change known and trusted protocols. A second approach, and one which may help to boost confidence in monitoring procedures, is to improve rapid diagnostic techniques (RTDs), so that when infection is suspected, it can be confirmed or ruled out more quickly. At present, suspected infections are confirmed by culture growth from blood samples. This can take days or, in the case of some diseases, even months to confirm.

In addition, the TATFAR report identified that many doctors prescribe antibiotics to patients as a first attempt at treating an infection. Antivirals may be prescribed only if the first drugs fail to have an effect, while antibiotics may be prescribed to patients the doctor suspects of having a viral infection while the real cause is being diagnosed because the patient expects to be given 'something'.[15] This practice has been widely confirmed to RUSI during informal scoping for a larger research project on the topic, the results of which will be incorporated into a joint workshop on AMR organised by RUSI in early 2013.

Funding and endorsing research into rapid diagnostics by organisations such as the WHO, which recently endorsed a novel test for TB and MDR-TB that has the potential to provide an accurate diagnosis in 100 minutes compared to the current three months,[16] should be encouraged by governments and academic funding councils worldwide. Rapid diagnostics could then be applied to all travellers on departure from known disease hotspots, not just aspiring immigrants, and all hospital patients in whom infection is suspected.

Misdiagnosis of viral infections as bacterial ones can also be improved by raising awareness amongst healthcare staff of when and where outbreaks of viral infections are occurring: a study by the American College of Physicians showed that from April 2009 to March 2010, during the H1N1 'Swine Flu' pandemic, antibiotic prescriptions decreased as the number of cases doctors saw increased their familiarity with the viral infection and led to more accurate diagnoses. [17]

Mapping the Spread of Disease

A third approach is to fund research and development into understanding of, and ways to limit, the spread of diseases, primarily by limiting the opportunities for infected individuals to come into contact with those who are not. It is here that lessons identified from AMR have the most potential to influence pandemic resilience planning more generally, as well as preparedness for a bioterrorist attack. Opportunities to explore more radical approaches, such as the use of social media and the internet, could test how infected individuals might access healthcare and other services online (thus preventing them from spreading the infection en route to, and home from, local healthcare facilities), or assess the impact of decentralising many medical services from large hospitals back into the community, even to home-based care. Similarly, intelligent use of social media could help to map the spread of the disease in the early stages, identifying outbreak 'hot spots', encouraging the development of social self-help networks and disseminating information from official and peer-to-peer networks.

Such approaches might also look at changing the way in which the benefits of vaccination and immunization programmes are communicated to the public. While the UK government promoted flu vaccinations to the entire population rather than just vulnerable groups during the Swine Flu pandemic, there was little uptake amongst healthy individuals once it was realised that symptoms were comparably mild. A healthy, young individual may well be able to fight off the effects of infection relatively easily, but a healthy, young, vaccinated individual will not pass on the disease to his frail ninety-year-old neighbour whose health is more likely to be affected. Vaccination programmes, and even better personal hygiene such as handwashing and covering one's mouth during coughing, often have a greater benefit to the community than to the individual but this is not always well communicated.

AMR is, clearly, a serious and ongoing concern. Many of the ways in which we can build resilience to it are relatively simple, but involve a willingness to move away from the prescription and use of antimicrobial drugs where infection is only suspected or possible; to a focus on use only where it has been definitely identified, and to improve diagnostic techniques to ensure that such infections can be confirmed as early as possible. If not, there is a real danger that we face a future in which medical techniques taken for granted during the past century become obsolete by the next. As James M. Hughes, President of the Infectious Diseases Society of America (IDSA) remarked when the society published its 2011 policy paper Combating Antimicrobial Resistance: Policy Recommendations to Save Lives,[18] 'the way we've managed our antibiotics for the past 70 years has failed ... we have a moral obligation to ensure they are available for future generations'.[19]

On 22 November 2012, following European Antibiotic Awareness Day, Professor Neil Woodford of the Health Protection Agency gave a presentation on ‘Antimicrobial Resistance: A Growing Concern for Healthcare Security and Resilience’ at RUSI. Professor Woodford’s presentation can be downloaded in the Downloads section on the right hand side of this page.

RUSI will be organising a joint workshop on this subject in February 2013. For further information, email jenniferc@rusi.org

Notes

[1] World Health Organization Fact sheet No194, Antimicrobial resistance, Reviewed March 2012.

[2] National Risk Register of Civil Emergencies, 23 August 2012.

[3] English National Point Prevalence Survey on Healthcare-associated Infections and Antimicrobial Use, 2011, Health Protection Agency, July 2011.

[4] Drug-resistant tuberculosis now at record levels, WHO Press Release last accessed 22 August 2012.

[5] Six out of a total 24 cases; figures provided by Department of Health August 2012.

[6] Migrant Health, A Baseline Report, 2 Tuberculosis,  Health Protection Agency.

[7] Damian Green, Home Office Statement, 21 May 2012.

[8] Controlling our Borders: Making Migration Work for Britain, Home Office, Cm 6472, last accessed 22 August 2012.

[9] English National Point Prevalence Survey on Healthcare-associated Infections and Antimicrobial Use, 2011, Health Protection Agency, May 2012, last accessed 8 August 2012.

[10] Antimicrobial (Drug) Resistance, US National Institute for Infectious Diseases, last accessed 6 August 2012.

[11] Combating Antimicrobial Resistance: Policy Recommendations to Save Lives, Clinical Infectious Diseases, IDSA, 2011, last accessed on 6 August 2012. 

[12] CG149 Antibiotics for early-onset neonatal infection: NICE guideline, National Institute for Health and Clinical Excellence, August 2012, last accessed 22 August 2012.

[13] Antibiotics for early-onset neonatal infection: antibiotics for the prevention and treatment of early-onset neonatal infection,  National Institute for Health and Clinical Excellence.

[14] Based on figures obtained in a Freedom of Information Request from Chelsea and Westminster Hospital NHS Trust (of an average of cost of £1,480.90+£1,023.78+£18.44 to treat a baby with suspected infection in the Special Care Baby Unit for 48 hours, using Cefotaxamine, while the mother remains on a postnatal ward, giving an average cost of £2,523.12) and from the Office of National Statistics (ONS) of 723,165 live births in 2010.

[15] Transatlantic Taskforce on Antimicrobial Resistance, Recommendations for future collaboration between the US and EU, 2011, last accessed 6 August 2012.

[16] WHO Endorses Rapid Tuberculosis Test, last accessed 8 August 2012.

[17] C. Herbert, et al, 'The Influence of Context on Antimicrobial Prescription for Febrile Respiratory Illness: A Cohort Study', Annals of Internal Medicine, (Vol 157, No.3, August 2012), available at <http://annals.org/article.aspx?articleid=1305509>.

[18] Strengthening U.S. Antibiotic Resistance Efforts, Infectious Diseases Society of America (IDSA).

 

[19] Reported in Science Daily, April 7 2011,  last accessed 8 August 2012.