The new UK antimicrobial resistance strategy and action plan
BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f1601 (Published 11 March 2013) Cite this as: BMJ 2013;346:f1601
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Setting the new UK antimicrobial resistance strategy in a wider context
The editorial reviewing the Chief Medical Officer’s intentions for tackling the rise of antimicrobial resistance (AMR) in her annual report is to be welcomed as it draws attention to this serious insidious threat to human health(1). The remarkable success of the co-ordinated actions within the NHS to reduce MRSA bacteremia to less than 2% exposes the rapidly growing problem of bacteremia caused by Gram negative bacteria, in particular E. coli (36%) and to a lesser extent Klebsiella (7.8%) (2). E. coli differs from almost all of the other causative agents of bacteremia in that endogenous infections predominate that usually arise from prior gut carriage. The ecology of acquisition, carriage and transmission of E. coli is poorly understood particularly in the community.
The human gut E. coli population and its associated resistance genes (resistome) are in dynamic connection to the wider environment and food animals (3). This intimate connection was the subject of an important symposium recently, the issue being addressed as “One medicine, one problem” (4) . The symposium recommendations presage the CMO’s action areas: promoting evidence based prescribing with behaviour change in both the profession and the public, improved diagnostics and facilitating the development of new antimicrobials. Because of its broader remit the symposium strongly identified the international dimension of the problem of multidrug resistant E. coli/Klebsiella, which is briefly mentioned in the CMO’s report. E. coli/Klebsiella which produce extended spectrum β-lactamases (ESBLs), usually CTX-M genotypes, are resistant to third generation cephalosporins (cefotaxime, etc), quinolones and most antibiotics other than carbapenems thus driving carbapenem usage and subsequent resistance(5). The extended spectrum β-lactamase rate in E. coli isolated from intra abdominal infections in 2008 in both India and China was 60%(6), whereas the same international surveillance project reported a rate of 16.9% for the UK(7). The reasons for this large differential in AMR is most probably accounted for by the heavy and relatively uncontrolled use of antibiotics in both human medicine and an increasingly industrialised food production systems coupled with water/sewage systems of variable quality in those countries. ESBL producing and quinolone resistant E. coli are identified at very high rates in food producing animals in these parts of the world, notably recently in farmed fish in China, which produces 62% of world production(8). In an increasingly connected world movement of E. coli particularly via human travel as evidenced by the 22.8% carriage rate of ESBL E. coli in individuals in the community in the UK of Middle Eastern/South Asian origin versus 8.1% in Europeans(9). Strategies to control antimicrobial resistance in human and veterinary medicine must recognise that the threat from outside Europe is potentially overwhelming. In addition to pursuing all reasonable measures to reduce the emergence and proliferation of AMR in the UK, our national strategies need to consider measures to reduce, identify (through surveillance) and deal with imported problems, be they in humans, food or animals.
Reference List
(1) Kessel AS, Sharland M. The new UK antimicrobial resistance strategy and action plan. BMJ 2013;346:f1601.
(2) Ridge KW, Hand K, Sharland M, Abubakar I, Livermore D. Annual Report of the Chief Medical Officer, Volume Two, 2011. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil...
(3) Wellington EM, Boxall AB, Cross P, Feil EJ, Gaze WH, Hawkey PM, et al. The role of the natural environment in the emergence of antibiotic resistance in gram-negative bacteria. Lancet Infect Dis 2013 Feb;13(2):155-65.
(4) Scientific Advisory Committee of the symposium. Communique from AMR Symposium October 2012. Available from: http://www.rcvs.org.uk/document-library/communique-from-amr-symposium-oc...
(5) Hawkey PM, Livermore DM. Carbapenem antibiotics for serious infections. BMJ 2012;344:e3236.
(6) Hsueh PR, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, Ni Y, et al. Epidemiology and antimicrobial susceptibility profiles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region: 2008 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Int J Antimicrob Agents 2010 Nov;36:408-14.
(7) Hawser S, Hoban D, Bouchillon S, Badal R, Carmeli Y, Hawkey P. Antimicrobial susceptibility of intra-abdominal gram-negative bacilli from Europe: SMART Europe 2008. Eur J Clin Microbiol Infect Dis 2011 Feb;30(2):173-9.
(8) Jiang HX, Tang D, Liu YH, Zhang XH, Zeng ZL, Xu L, et al. Prevalence and characteristics of beta-lactamase and plasmid-mediated quinolone resistance genes in Escherichia coli isolated from farmed fish in China. J Antimicrob Chemother 2012 Oct;67(10):2350-3.
(9) Wickramasinghe NH, Xu L, Eustace A, Shabir S, Saluja T, Hawkey PM. High community faecal carriage rates of CTX-M ESBL-producing Escherichia coli in a specific population group in Birmingham, UK. J Antimicrob Chemother 2012 May;67(5):1108-13.
Competing interests: No competing interests
This week’s slew of articles focusing on the issue of antimicrobial resistance raise important points about the future challenges of providing healthcare in a world where the previous assumptions about antibiotic treatment effectiveness will have changed 1–4. While further increments in antibiotic stewardship are critical, new and novel agents are required, particularly to address those increasingly prevalent organisms with inherent natural resistance to current antimicrobials (e.g. Acinetobacter baumannii) and those acquiring new resistance mechanisms (e.g. E. Coli and Klebsiella spp.), yet the pipeline of new classes of antimicrobial pharmaceuticals is running dry 5, 6.
Although touched on in these articles, the reasons for the dearth of new antimicrobial agents coming to market have perhaps not been given the attention they deserve.
In order to understand why few new antimicrobial agents are in the pipeline, it is necessary to examine basic economic theory. Porter’s 5 forces model of the dynamics of a competitive market place provide some useful insights 7. The antimicrobial marketplace (and the incentives to invest in new products) is influenced by the balances between the bargaining power of customers (patients / healthcare suppliers / governments) and suppliers (pharmaceutical companies / biotech startups) and the threat of substitutes (other companies’ products including generics) and new entrants (generics companies). Currently the balance is tipped in favour of antibiotic products being available at low cost relative to their social benefit. In addition, the high costs of bringing a new antibiotic to the market and the potential short life span (due to resistance) of any new product, all make the antimicrobial pharmaceutical business an unattractive one in which to invest / remain in 8.
Antimicrobial agents are cheap relative to their therapeutic and social benefit. For example, in the UK a seven day course of amoxicillin (250mg three times daily) costs 95p, and a lifesaving course of ceftriaxone for the treatment of meningococcal meningitis costs less than £142.52 (both treatments which can give many years of productive life for the individual and society after recovery) 9 10. Yet, society is prepared to pay substantially more for treatments where life expectancy may be more limited e.g. the use of trastuzumab (Herceptin ®) in metastatic breast cancer can cost many thousands of pounds (each vial costs £407.40) 11. Tackling this paradox has to be part of the solution to antimicrobial resistance.
Mossialos et al. examined the therapeutic benefit / social benefit pricing of antimicrobials and concluded that pricing based on their benefits to society and the individual could incentivise the development of new antimicrobial agents 8. This has some merit, however, would probably work best where the primary consumer is separated from the direct payment and also where the price paid for each agent is readily influenced. The UK is in such a position – a universal drug tariff, coupled with no direct consumer payment for inpatient antimicrobial therapy and fixed price costs (for consumers) for antimicrobials prescribed in the community would allow policy makers in the UK to take a lead in remodelling the antimicrobial therapy market.
Unless the fundamental mechanisms leading to the current market failure are addressed, it is probable that little progress will be made in improving the flow of new / novel classes of antimicrobials. Indeed it would appear that progress over the last 10 years has been limited. Livermore noted in 2003, that many statements had already been made about the urgency of the problem and that new antimicrobial agents were needed, yet a decade later we are still faced with few new drugs and classes of antimicrobials 5, 12 A paradigm shift in approach is needed, perhaps starting with a dialogue with pharmaceutical companies as to the prerequisites needed to incentivise new antimicrobial development.
References
1 Godlee F. Antimicrobial resistance--an unfolding catastrophe. BMJ 2013;346:f1663–f1663.
2 Kessel AS, Sharland M. The new UK antimicrobial resistance strategy and action plan. BMJ 2013;346:f1601–f1601.
3 Smith R, Coast J. The true cost of antimicrobial resistance. BMJ 2013;346:f1493–f1493.
4 Torjesen I. Antimicrobial resistance presents an “apocalyptic” threat similar to that of climate change, CMO warns. BMJ 2013;346:f1597–f1597.
5 Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003;36:S11–23.
6 Antibiotic Action. http://antibiotic-action.com/whatwedo/ (accessed 19 Mar2013).
7 Porter ME. Towards a dynamic theory of strategy. Strategic Management Journal 1991;12:95–117.
8 Mossialos E, Morel C, Edwards S, et al. Policies and incentives for promoting innovation in antibiotic research. London:
9 Amoxicillin: British National Formulary. In: British National Formulary. London: : BMJ Group and Pharmaceutical Press 2013. 5.1.2.1.
10 Ceftriaxone: British National Formulary. In: British National Formulary. London: : BMJ Group and Pharmaceutical Press 2013. 5.1.2.1.
11 Trastuzumab:British National Formulary. In: British National Formulary . London: : BMJ Group and Pharmaceutical Press 2013. 8.1.5.
12 Kirby T. Europe to boost development of new antimicrobial drugs. The Lancet 2012;379:2229–30.
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: RP is Associate Professor of Health Protection at the University of Nottingham and Honorary Regional Epidemiologist for the Health Protection Agency East Midlands. RP commented on the draft DH strategy and action plan which led to some modifications. The views expressed here are his own and do not represent those of the University or HPA.
Re: The new UK antimicrobial resistance strategy and action plan
One point not often mentioned in relation to spread of antibiotic resistant organisms is whether improved monitoring of hospital ventilation, heat and humidity at the patient level on the ward would help reduce the cross infection risk. In my experience, many patients complain of hot, humid wards (1), both in mechanically ventilated hospitals and in hospitals with natural ventilation (where window opening is restricted to 10cm to prevent suicides & falls (2).)
The large amount of heat-producing electrical equipment in hospitals (computers, medical equipment, televisions, bright lights, refrigerators, fans etc) must be giving heat increases far in excess of those in even the relatively recent past. In general, as temperature increases, so relative humidity decreases but this requires an adequate air flow at patient (& commode) level. If air changes are not adequate, water vapour and steam from kitchens and bathrooms will not be so easily lost through evaporation. Also, surfaces will dry more slowly. Bacteria including antibiotic resistant Gram-negative bacilli and some respiratory viruses will survive in areas which are moist and warm (3).
When humidity increases, sufficient air changes are also needed to allow evaporation of perspiration (which helps regulate body temperature). Under warm, humid conditions, both staff and patients will be less able to lose body heat and sweat will not evaporate so easily from the skin. Moist hands will acquire and transmit both antibiotic resistant and antibiotic sensitive organisms more readily than dry hands (4-7)
With intensive bed use and high occupancy rates, adequate air changes are also necessary to refresh the air (8) and dilute the airborne bacterial load.
There are no official NHS regulations on heat and humidity. To maintain acceptable levels, alterations to naturally ventilated areas may not be expensive. One study showed that air-borne spread of organisms (using Mycobacterium tuberculosis as an example) was less with openable doors and windows than in some more expensive mechanically ventilated areas. (9)
Proper control of hospital temperature and humidity is overdue and air changes at patient level should be monitored regularly -- and would also provide a much more comfortable environment for the patient.
References
1. Williams M BMJ Rapid Responses 27.6.2008 A breath of fresh air
2. NHS Estates Health Technical Memorandum 55 Windows 98.
3. Price EH, Ayliffe G. Hot hospitals and what happened to wash, rinse and dry? Recent changes to cleaning, disinfection and environmental ventilation
J Hosp Infect 2008 ; 69(1): 89-91
4. Merry AF, Miller TE, Findon G, Webster CS, Neff SP. Touch contamination levels during anaesthetic procedures and their relationship to hand hygiene procedures: a clinical audit. Br J Anaesth 2001;87(2):291-294.
5. Marples RR, Towers AG. A laboratory model for the investigation of contact transfer of micro-organisms. J Hyg (Lond) 1979;82(2):237-248.
6. Hill HW, Mathews H. Transfer of infection by handshakes. The Public Health Journal 1926:(7):347-352.
7. Patrick DR, Findon G, Miller TE. Residual moisture determines the level of touch-contact-associated bacterial transfer following hand washing. Epidemiol Infect 1997;119(3):319-325.
8. Clements-Croome DJ, Awbi HB, Bako-Biro Zs, Kochhar N, Williams M. Ventilation rates in schools. Building and Environment 2008; 43:362-367
9. Escombe AR, Oeser CC, Gilman RH, Navincopa M, Ticona E, Pan W. Natural ventilation for the prevention of airborne contagion PLoS Med 4(2):e68. doi:10.1371/journalpmed0040068
Competing interests: No competing interests