Tackling the threat of antimicrobial
resistance: from policy to sustainable
rstb.royalsocietypublishing.org
Opinion piece
Cite this article: Shallcross LJ, Howard SJ,
Fowler T, Davies SC. 2015 Tackling the threat of
antimicrobial resistance: from policy to sus-
tainable action. Phil. Trans. R. Soc. B 370:
20140082.
http://dx.doi.org/10.1098/rstb.2014.0082
Accepted: 9 February 2015
One contribution of 9 to a theme issue
‘Antimicrobial resistance: addressing the threat
to global health’.
Subject Areas:
microbiology, health and disease and
epidemiology
Keywords:
antimicrobial resistance, public health,
policy, global health
Author for correspondence:
Laura J. Shallcross
e-mail: laura.shallcross@dh.gsi.gov.uk
action
Laura J. Shallcross1,2, Simon J. Howard3, Tom Fowler4,5
and Sally C. Davies1
1
Department of Health, Office of the Chief Medical Officer, 79 Whitehall, London SW1A 2NS, UK
2
Research Department of Infection and Population Health, University College London, 222 Euston Road,
London NW1 2DA, UK
3
North East Health Protection Team, Public Health England, Gallowgate, Newcastle-upon-Tyne NE1 4WH, UK
4
Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London EC1M 6BQ, UK
5
Public Health, Epidemiology and Biostatistics, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Antibiotics underpin all of modern medicine, from routine major surgery
through to caesarean sections and modern cancer therapies. These drugs have
revolutionized how we practice medicine, but we are in a constant evolutionary
battle to evade microbial resistance and this has become a major global public
health problem. We have overused and misused these essential medicines
both in the human and animal health sectors and this threatens the effectiveness
of antimicrobials for future generations. We can only address the threat of anti-
microbial resistance (AMR) through international collaboration across human
and animal health sectors integrating social, economic and behavioural factors.
Our global organizations are rising to the challenge with the recent World Health
Assembly resolution on AMR and development of the Global Action plan but
we must act now to avoid a return to a pre-antibiotic era.
1. Introduction
Antimicrobial resistance (AMR) existed long before antimicrobials were har-
nessed for use by humans. It develops through a Darwinian process of natural
selection: those microbes which are resistant to an antimicrobial continue to
thrive in its presence, and hence gain a selective advantage. Many forms of resist-
ance are dependent on enzyme action; those microbes with resistance pass the
genes encoding for the enzymes to the next generation, and so forth. The picture
is complicated, and the process hastened, by the intra-generational genetic
sharing mechanisms which some bacteria possess.
Antibiotics have been used to treat bacterial infections since the mid-twentieth
century, and resistance of human bacterial infections to antibiotics has been
described ever since. When giving his Nobel lecture following the discovery of
penicillin, Fleming sounded a warning about resistance [1, p. 93]
It is not difficult to make microbes resistant to penicillin in the laboratory by exposing
them to concentrations not sufficient to kill them, and the same thing has occasionally
happened in the body.
Antibiotics contributed to a major shift in patterns of mortality, both in the UK
and worldwide. In 1900, before the discovery of penicillin in 1928, respiratory
and gastrointestinal infections accounted for an estimated one-third of total
deaths. In less than a century, there has been a major decline in deaths from
infectious diseases, although respiratory tract infections such as pneumonia
and influenza still feature in the top 10 leading causes of death in high-
income countries [2]. One of the primary reasons for this continued medical
success despite the growth of resistance has been the continuous development
of new classes of antibiotics, which have different mechanisms of action. Bac-
terial infections that have developed resistance to one or multiple classes of
& 2015 The Author(s) Published by the Royal Society. All rights reserved.
 1200
1000
800
frequency
600
400
200
0 mandatory surveillance system, 2002 – 2010. Source: Johnson et al. [6].
2003
2004
2005
2006
2007
2008
2009
IMP VIM KPC OXA-48 NDM IMI
Figure 1. Carbapenemase-producing Enterobacteriaceae confirmed by PHE-
AMRHAI-Colindale from UK laboratories. IMP, Imipenemase metallo-b-lacta-
mase; VIM, Verona integron-encoded metallo-b-lactamases; KPC, Klebsiella
pneumoniae carbapenemases; OXA-48, Oxacillinase-48; NDM, New Delhi
metallo-b-lactamase; IMI, Imipenem-hydrolysing b-lactamases. Source:
Public Health England. (Online version in colour.)
antibiotics can still be treated by using antibiotics with a
different mechanism of action, either alone or in combination
with other antibiotics.
Provided there is a continued supply of new antibiotics, we
may be able to keep pace with the emergence of drug-resistant
strains. However, discovery of new classes of antibiotics stalled
in the mid-1980s and few have been discovered over the last
quarter of a century [3]. Partly as a consequence of this, isolates
are now appearing which are resistant to all antibiotics in our
armoury, raising the spectre of untreatable infection even at
the world’s most advanced medical centres [4]. Excitingly,
within the last month, a new antibiotic called teixobactin has
been developed, using novel methods to cultivate soil bacteria
[5]. Teixobactin has good activity in vitro against gram-positive
bacteria including drug-resistant strains, but it is yet to be
trialled in humans.
In the UK, national surveillance of resistance comprises
routine testing of bacterial samples for resistance to a wide
panel of antibiotics. This includes testing samples for resistance
to the carbapenem class of antibiotics, widely regarded as the
class of last resort for drug-resistant infections. Until 2003, car-
bapenem-resistant strains were extremely rare in both the UK
and Europe. Since then, there has been an exponential rise in
the number of carbapenem-resistant infections in the UK
(figure 1), and these are hard to treat. Most worrying of all, sur-
veillance has recently identified half a dozen clinical isolates
within the UK which are resistant to all tested antibiotics:
that is, infections which are effectively untreatable because of
resistance are now present in the UK, albeit at an extremely
low prevalence.
2. Responding to the threat of antimicrobial
resistance
While AMR has long been recognized as a threat to human
health, in recent years many countries have focused on
9000 2
8000
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MRSA bacteraemias (no.)
7000
6000
4000
4000
3000
2000
1000
0
Phil. Trans. R. Soc. B 370: 20140082
2002 2003 2004 2005 2006 2007 2008 2009 2010
year
Figure 2. Number of MRSA bacteraemias in England reported through the
2010
2011
2012
2013
KPC + VIM NDM + OXA-48
reducing healthcare-acquired infections such as methicillin-
resistant Staphylococcus aureus (MRSA) and Clostridium difficile
infection (CDI) (figure 2). This has led to a significant reduction
in the incidence of both MRSA and CDI within hospitals in the
UK and a major decline in prescribing of cephalosporins and
fluoroquinolones. Arguably, this success has shifted attention
away from AMR, allowing it to escalate. Despite concerted
efforts from 1998 onwards, through a series of World Health
Assembly (WHA) resolutions and the 2001 WHO global strat-
egy for containment of AMR, the need to accelerate progress on
AMR has been widely acknowledged by the WHO, the USA
and the European commission.
In 2012/2013, the publication of several landmark reports
from organizations and individuals including the World Econ-
omic Forum [7], the US Centers for Disease Control [8] and
the Chief Medical Officer for England [9] has led to a renewed
international focus on AMR. The CMO’s report highlighted
infections and the rise of resistance, drawing national and
global attention to this problem. A new UK-wide cross-
government AMR strategy was developed and published in
2013 [10], building on the previous 2001 strategy with some
important refinements. The ‘One Health’ approach was inter-
preted more broadly to encompass collaboration not only
across human and animal sectors but also economic, social
and behavioural components with a focus on collaborative
action in this area. The new strategy had a major focus on
measuring outcomes alongside an innovative combination of
policy approaches to stimulate research and development,
improve surveillance, prevent and control infection, optimize
antimicrobial use and relay key AMR messages to public
and professional audiences. AMR was quickly placed on
the risk registers of both the Department of Health and the
Department for Environment, Food and Rural Affairs and
the CMO called for inclusion on the Government risk register
as part of the national security risk assessment making AMR
a cross-government priority.
Though important for the UK, this action alone could not
drive the collaborative response and commitment that was
required from governments across the world. This demanded
a strategic approach: maximizing political influence, enga-
ging with the public and working to develop the scientific
evidence-base to deliver new antimicrobials.
The UK maximized its influence by working across gov-
ernment to raise AMR on the political agenda worldwide.
The CMO capitalized on her high-profile position as
independent advisor to the UK Government to convey a
compelling narrative on the threat of AMR and reach out to
civil society through activities such as her TEDx talk,
‘The Drugs Don’t Work’, and Penguin book of the same
name. The scientific case was apparent: the burden of drug-
resistant infections was increasing with no new antibiotics
in the pipeline. Nonetheless, it has been essential to build
the evidence-base by obtaining an accurate global picture
of the magnitude of AMR and national surveillance capacity
through the WHO 2014 report on global surveillance,
highlighting the need for capacity building.
While there was global recognition of the importance of
AMR, including a number of separate national initiatives, in
the period immediately after publication of the CMO’s
report in 2011 there was no clear mechanism for collaborative
international efforts. Driven by the UK and Sweden, a resol-
ution on AMR was drafted and ratified at the 67th WHA in
2014. This gave the WHO a mandate to develop a global
action plan, legitimizing action on behalf of member states.
The draft action plan acknowledges that member states will
have different priorities in relation to AMR so it has been
devised as a series of building blocks [11]. Member states are
encouraged to develop action plans that focus interventions
on where nationally they are most needed.
Under the influence of the UK, the broader interpretation of
the ‘One Health’ concept has been more widely adopted. The
UK continues to provide leadership in this area, as was evident
from the recent One Health Conference at The Hague (June
2014) in which the UK was one of the few countries to send
representatives from both human and animal health sectors,
the Chief Medical and Veterinary Officers and Ministers,
respectively. This broader approach has led to recognition in
government that this is not solely a health issue, but that
AMR encompasses economic, social and security consider-
ations. In response to this, the Prime Minister, David
Cameron, established an economic review by Jim O’Neill on
AMR with the recent publication of the first paper focusing
on the macroeconomic impact of increasing AMR [12]. This
suggests that drug-resistant infections will cost the world 10
million extra deaths per year and up to 100 trillion dollars by
2050 if action is not taken to reduce AMR (figure 3).
The success of the AMR strategy and action plan depends
on strong practical support, infrastructure and high-quality
data. While the UK has taken a strong leadership role,
other countries have also demonstrated leadership. The
USA-led Global Health Security Agenda includes a pro-
gramme, co-led by the UK, specifically focused on AMR in
order to provide support for countries to build infrastructure
to work towards the goals outlined in the action plan. Along-
side this work, a meeting in Stockholm was convened to
discuss WHO-led coordination of surveillance data to ensure
that the impact of action against the plan can be monitored.
The world is looking to the UK for leadership on AMR.
Our leadership can be shown not just through our action
on the international stage, but also through the domestic
action we are taking. We need to put our own house in
order if we are to advocate vigorously in the international
arena. By publishing an annual progress report, we are hold-
ing ourselves to account: highlighting our successes to share
our learning, and also identifying areas of weakness where
we must do more [13]. The UK now has one of the world’s
most effective surveillance systems for monitoring AMR
and prescribing [14]. This is great progress, but surveillance
AMR in 2050 3
10 million
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tetanus
60 000
road traffic
accidents cancer
1.2 million 8.2 million
AMR now
700 000
(low estimate)
measles
Phil. Trans. R. Soc. B 370: 20140082
cholera
130 000 100 000–
120 000
diarrhoeal
disease diabetes
1.4 million 1.5 million
Figure 3. Annual deaths attributable to AMR compared to other major
causes of death. Source: Antimicrobial resistance: tackling a crisis for the
health and wealth of nations. Review on Antimicrobial Resistance [12].
(Online version in colour.)
is still limited, particularly in relation to antimicrobial use
in hospitals. The uniformity of antimicrobial policies across
NHS Trusts for the treatment of common infections needs
to be improved, but without driving selection pressure for
resistance by overreliance on a few key drugs. This is being
addressed through the development of short syndrome-
specific guidance on the management of common infections
in hospitals, coordinated by the Governmental Advisory
Group on AMR and healthcare-associated infections
(ARHAI) and the National Institute of Healthcare Excellence
(NICE). These guidelines will sit in the context of a prescrib-
ing framework to promote antibiotic stewardship including
prescribing diversity, lessening the risk of AMR associated
with intensive use of a few antibiotic classes. This will
build on existing stewardship initiatives such as ‘Start
Smart then Focus’ and the soon to be published antimicrobial
stewardship guidance from NICE.
We have established an AMR Research Funders’ Forum,
led by the Medical Research Council, which brings together
major research funders and government to ensure evidence
is developed to better understand the relationship between
AMR in animals and humans, laying a solid foundation for
policy. This is essential because understanding of the AMR
ecosystem is limited, and although progress has been made
in collecting data from the human and animal health sectors,
methods for linking and interpreting this combined data are
yet to be developed.
The UK has played a pivotal role in galvanizing internatio-
nal action on AMR and we must continue to demonstrate
leadership in this area. By supporting international partner-
ships and coalitions, we can facilitate the development of new
antibiotics and other treatments. We can seek assurance from
the WHO and the EU of their commitment to accelerate pro-
gress on AMR and work with the WHO to support the
development of the global action plan on AMR.
Most clinicians recognize the importance of antimicrobial
stewardship but there is an intrinsic tension between balancing
the risk to an individual patient thought to have an infectious
disease and the need to protect the population through
prevention of the development of AMR. An abundance of clini- number of longer hospital admissions. Indeed, infection-related 4
cal caution can drive practitioners towards inappropriate mortality rates may increase to a level comparable with those in

antibiotic use and this may be mitigated by the use of robust,
evidence-based clinical guidelines; rapid diagnostics could
also play a key role of targeting antibiotic use. Without clinical
leadership across specialties, it will prove difficult to have
an impact on antibiotic prescribing in hospitals through
initiatives such as ‘Start Smart then Focus’ [15].
There is good evidence that public campaigns around anti-
biotics lead to reduction in use. The individual impact of
various public campaigns in Europe between 1997 and 2007
has been estimated to be equivalent to a 6.5–28.3% drop in
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the Victorian era.
The threat of AMR is grave; but there are glimmers of
hope. Examples of healthcare-associated infections show
that concerted, sustained and unwavering action can deliver
results. Cases of MRSA in hospitals in England have declined
by 87.3% from their peak in 2003, and C. difficile infections
have fallen by over 60% from their peak in 2007. Yet, these
successes lie against a background of a sustained increase
in mortality attributable to infections caused by antimicrobial
resistant bacteria as a whole.

Phil. Trans. R. Soc. B 370: 20140082

the mean level of antibiotic use [16,17]. The response of the
public to European Antibiotic Awareness Day in November
2013 saw unprecedented levels of online access to educational
materials, with more than 12 000 people pledging to become an
antibiotic guardian when the campaign was refreshed in
November 2014 [18]. Whether the recent actions of many
health leaders to raise public awareness of this issue through
depicting a post-antibiotic era can be considered equivalent
to a public campaign is unclear, but it seems likely that they
will have had some impact.
Public support for action to tackle AMR is crucial, as
many measures to mitigate the effects of resistance will
incur substantial financial and societal costs, which will ulti-
mately be borne by the public, both through taxation and,
probably, through higher purchase costs of products whose
manufacturing methods are altered. For example, a pricing
paradox exists in farming whereby antibiotics, an increasingly
scarce natural resource, cost less than implementation of more
rigorous hygiene practices. Reversal of this paradox may lead
to higher food prices. While these costs are undoubtedly
lesser than the long-term cost of unmitigated antibiotic resist-
ance, they are also more immediate and, superficially at least,
discretionary.
If AMR is allowed to continue unchecked, we may enter a
‘post-antibiotic era’ of medicine, in which treatments from
minor surgery to major transplants could become impossible,
mortality will rise, and healthcare costs will spiral as we
resort to newer, more expensive antibiotics and sustain a greater
The Royal Society can play a key role in helping to tackle
AMR. Strong scientific support for this agenda, targeting
AMR research and development of the basic science is badly
needed. The scientific challenge is both broad and deep. We
require discovery or creation of new drugs with different anti-
microbial properties at the molecular level; invention of rapid
diagnostic tests on the broader technological level and
improved understanding of ways to influence antibiotic prac-
tice in the medical community and beyond on the social
level; as well as new vaccines to prevent infection. We need
to further improve surveillance systems on a global level and
facilitate data sharing. And we need to develop new economic
models to ensure that development of new antibiotics and tech-
nologies is a viable prospect for industrial partners. All such
endeavours require sustained high-level scientific support, in
terms of action and funding in addition to rhetoric.
If we are to protect the world’s population today and for
generations to come, then there is much more work to be done.
Acknowledgements. Data presented in figure 1 was provided by Prof.
Neil Woodford, Public Health England-AMRHAI.
Author contributions. All authors contributed to the conception of the
article. L.J.S., S.J.H. and T.F. prepared the first draft of the manuscript.
S.C.D. revised and edited the manuscript. All authors approved the
final version of the manuscript.
Funding statement. No funding was obtained for this article.
Conflict of interests. S.C.D. is Chief Medical Officer for England and chairs
the WHO Strategic and Technical Advisory Group (WHO-STAG) on
AMR. All other authors declare no conflict of interest.

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