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The true cost of antimicrobial resistance

11 Mar 2013-BMJ (British Medical Journal Publishing Group)-Vol. 346
TL;DR: Richard Smith and Joanna Coast argue that current estimates of the cost of antibiotic resistance are misleading and may result in inadequate investment in tackling the problem.
Abstract: Richard Smith and Joanna Coast argue that current estimates of the cost of antibiotic resistance are misleading and may result in inadequate investment in tackling the problem

Summary (1 min read)

Introduction

  • A rapid decrease in the number of new drugs approved and numerous withdrawals on quality and safety grounds have left the well dry, and it is clear that “the existing classes of antibiotics are probably the best the authors will ever have.”.
  • And even here the authors concluded that the evidence for the cost effectiveness of interventions for resistance was poor.
  • Most studies were from the United States and based in hospitals and included the costs related to additional hospital stay and treatment but not early mortality.
  • The authors searched for the combinations of terms relating to resistance, antimicrobial and costs.

A world without antibiotics

  • Modern healthcare was built over the past century on the basis that infections can be prevented or treated using antimicrobials (exemplified by the US surgeon general famously proclaiming in 1968 that “the war against diseases has been won”).
  • Healthcare has become increasingly technological and invasive, improving mortality and morbidity significantly, and antimicrobials have become integrated in many aspects of such care.
  • To calculate the true economic burden of resistance the authors therefore have to consider the burden associated with not having any effective antimicrobial drugs.
  • And, as witnessed when there are outbreaks of hospital acquired infection, the system can very quickly come to a standstill.

Planning for an uncertain future

  • Understanding the threat to the health system overall, not just for specific diseases, could be the single most important step in better understanding the economic burden that resistance presents.
  • The authors should view greater investment in antibiotic resistance as an insurance policy a rapid review, and interaction with colleagues who commissioned this review at the Department of Health.

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The true cost of antimicrobial resistance
Richard Smith and Joanna Coast argue that current estimates of the cost of antibiotic resistance
are misleading and may result in inadequate investment in tackling the problem
Richard Smith professor of health system economics
1
, Joanna Coast professor of health economics
2
1
London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK;
2
School of Health and Population Sciences, University of Birmingham.
Birmingham, UK
Almost as soon as antibiotics were discovered, we knew that
bacteria were able to develop resistance against them.
1
This is
not necessarily a problem, as long as there are other
antimicrobials to take their place. During the latter half of the
20th century this was the predominant situation, but no longer.
2
A rapid decrease in the number of new drugs approved and
numerous withdrawals on quality and safety grounds have left
the well dry, and it is clear that “the existing classes of
antibiotics are probably the best we will ever have.”
3
In light of this, there have been efforts to support interventions
that encourage more conservative and appropriate use of
antibiotics in an attempt to halt or slow the progress of
resistance.
4
However, this action is often too little and may be
too late.
Given that the dangers of resistance are widely acknowledged,
why isn’t more being done? One reason is that antibiotic
resistance has fallen victim to evidence based policy making,
which prioritises health problems by economic burden and cost
effectiveness of interventions.
5
Health economists have been
unable to show that antibiotic resistance costs enough to be a
health priority.
Limitations of health economic research
Ten years ago we published a systematic review on the
economics of resistance.
6
We asked two questions: what is the
cost of resistance and what is the cost effectiveness of
interventions to reduce it? The lack of research meant we could
investigate only the second question.
7
And even here we
concluded that the evidence for the cost effectiveness of
interventions for resistance was poor.
We have just performed a rapid review at the Department of
Health’s request to take into account newer information on the
first question. The box summarises our methods and further
details are available in the full report.
8
Estimates of additional
cost varied from less than $5 (£3; €4) to more than $55 000 per
patient episode. This might be explained by type of resistance
and how productivity losses are dealt with.
Although there was little intrinsically wrong with these papers,
we became concerned that their estimates of the actual economic
impact may not be accurate because the research used to produce
these estimates is limited in its scope. For example, economic
estimates are based on the incremental costs and focus on a
specific infectious disease or set of diseases: estimates are based
on the cost of extra treatment of a resistant infection compared
with susceptible infection, such as costs of additional
investigations, more expensive drugs, side effects from extra
treatments, longer hospital stay, and greater mortality.
9
Some
may also include costs associated with surveillance and activities
associated with trying to control resistance. Most studies were
from the United States and based in hospitals and included the
costs related to additional hospital stay and treatment but not
early mortality.
None of the studies considered the bigger picture—a world in
which there are no effective antibiotics for situations where they
are currently used routinely, such as in hip replacement or cancer
patients. Our concern is that today’s limited estimates will be
used to project future costs. Will the current worst case scenario
place antibiotics high enough up on the health agenda to ensure
adequate action?
Current worst case scenario is still an
underestimate
We took the study that found the highest cost of antimicrobial
resistance, of $55bn ($20bn in health service costs and $35bn
in lost productivity) per year overall to the US, and compared
it with economic burden figures for other health problems in
the US. These burden figures are taken from a variety of studies,
and the dates range considerably, but it is clear that resistance
rates fairly low down (table).
However, the costs of resistance could be much higher than
these estimates suggest. As an example we estimated the
consequences of having no antibiotics for patients having a total
hip replacement. Because antibiotics have been used as
Correspondence to: R Smith Richard.Smith@lshtm.ac.uk
Extra references w1-w17 supplied by the author (see http://www.bmj.com/content/346/bmj.f1493?tab=related#webextra)
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BMJ 2013;346:f1493 doi: 10.1136/bmj.f1493 (Published 11 March 2013) Page 1 of 5
Analysis
ANALYSIS

Box 1 Methods used in the review
8
We searched for the combinations of terms relating to resistance, antimicrobial and costs. Some papers did not refer to antimicrobial
resistance generally but only to particular drugs or micro-organisms. We extended the search terms to focus on meticillin resistant
Staphylococcus aureus and vancomycin resistant enterococci, two of the most studied and potentially serious current resistant infections.
We included English language studies (empirical or modelling) with data on costs associated with resistance, since 2000. For empirical
studies, we selected studies that included a control group with a susceptible infection because the aim was to focus on costs of resistance,
rather than costs of infection.
Data extracted included: study design; sample size/modelling approach; relevant micro-organism and drug; cost perspective, year, currency,
time frame, discounting approach; resource use included; valuation methods; summary of results.
We identified 192 possible papers, from which 24 were eventually included in our analyses.
prophylaxis and treatment for hospital acquired infection since
hip replacements were first performed we looked at information
relating to limb amputation as a proxy for what infection rates
might have been with and without antimicrobials.
The figure shows the care pathway for patients requiring hip
replacement. Currently, prophylaxis is standard practice, and
infection rates are about 0.5-2%, so most patients recover
without infection, and those who get an infection have it
successfully treated. We estimate that without antimicrobials,
the rate of postoperative infection is 40-50% and about 30% of
those with an infection will die.
w14-w17
Thus, removal of
antibiotics would increase postoperative infection by 1-50%
and deaths by 0-30%. Of course, at such rates it is likely that
the rates of hip replacement would fall, which would increase
the burden of morbidity from hip pain.
We recognise that this is a simplistic analysis, with many of the
data obtained from literature relating to amputation as a proxy
for hip replacement. However, we use it as an example to
illustrate and provoke, to emphasise the point that infection
rates and their consequences in terms of health service costs
and human health may be unimaginable. As we struggle to
imagine the clinical consequences, it is easy to see why the
economic burden is at present inestimable.
A world without antibiotics
Modern healthcare was built over the past century on the basis
that infections can be prevented or treated using antimicrobials
(exemplified by the US surgeon general famously proclaiming
in 1968 that “the war against diseases has been won”).
10
Resistance is said to present a risk that we will fall back into
the pre-antibiotic era.
11
However, this is perhaps optimistic. Our
health system is now designed to treat more chronic conditions.
Healthcare has become increasingly technological and invasive,
improving mortality and morbidity significantly, and
antimicrobials have become integrated in many aspects of such
care. For example, antimicrobials are given as standard to
prevent iatrogenic infection in surgical care,
11
to women
delivering by caesarean section,
12
and to those having cancer
treatment.
13
From cradle to grave, antimicrobials have become
pivotal in safeguarding the overall health of human societies.
When viewed in this broader way, the costs of resistance are
not limited to those associated with additional treatment for a
primary infection , such as a “strep throat.” Rather, they must
encompass the costs that might relate to the loss of modern
healthcare. In the same way that health systems need adequate
and effective health workers to function, they also require
effective antimicrobials. Resistance is not just an infectious
disease issue; it is a surgical issue, a cancer issue, a health
system issue.
To calculate the true economic burden of resistance we therefore
have to consider the burden associated with not having any
effective antimicrobial drugs. And, as witnessed when there are
outbreaks of hospital acquired infection, the system can very
quickly come to a standstill.
14
In the future we may need to
rethink how the health system is developed—for instance,
redesigning many facilities or reintroducing sanatoriums if
effective antibiotic treatments are no longer available.
Planning for an uncertain future
Although we now have more empirical information on the
economic burden of resistance than was available a decade ago,
it is unlikely to help us plan for the future. Even the highest
current estimates of the costs of resistance provide false
reassurance and this may mean that inadequate attention and
resources are devoted to resolving the problem. Our illustrative
example for hip replacement without antibiotics shows how
difficult it is to forecast the likely economic burden of resistance.
And we have explained how resistance has the potential to
undermine modern health systems.
Full health systems analyses seem a more appropriate means to
assess the potential impact of resistance and evaluate measures
to stem it. Although this approach is complex, understanding
the threat to the health system overall, not just for specific
diseases, could be the single most important step in better
understanding the economic burden that resistance presents.
Analysing outbreaks of resistant infections and the cost of
disruption to the heathcare system may help produce future
estimates.
15
A change in culture and action is needed to plan for a future
with more antibiotic resistance. Considerable inertia remains
regarding radical change in our stewardship of antimicrobials,
precisely because there is a focus on current economic burden.
The same is true with climate change and, to a degree, the
financial system. A major driver of this inertia is likely to be
collective uncertainty about the clinical and financial
implications of increasing resistance. But there is a tried and
trusted way to deal with such uncertainty—insurance. Waiting
for the burden to become substantial before taking action may
mean waiting until it is too late. Rather than see expenditure on
antimicrobial policies as a cost, we should think of it as an
insurance policy against a catastrophe; albeit one which we hope
will never happen.
9
We thank Callum Hodge, Joseph Griffin, and Daniel Haynes for help
with literature searching and Anthony So, Ursula Wells, Claire Boville,
Sally Wellsteed, Ross Leach, Peter Bennett, John Henderson, David
Cohen, Miranda Mugford, and Huseyin Naci for their comments. This
report is independent research commissioned and funded by the
Department of Health Policy Research Programme (Economic burden
of antimicrobial resistance: a rapid paper, 0410035). The views
expressed in this publication are those of the authors and not necessarily
those of the Department of Health.
Contributors and sources: Both authors have been health economists
for over 20 years and have worked together on aspects related to
antimicrobial resistance for more than 15 years. This article is a
culmination of experiences over that time, and is based particularly on
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BMJ 2013;346:f1493 doi: 10.1136/bmj.f1493 (Published 11 March 2013) Page 2 of 5
ANALYSIS

Key messages
An increase in resistant organisms coupled with a big fall in the number of new antimicrobial drugs suggests an apocalyptic scenario
may be looming
Current estimates suggest antimicrobial resistance has a low economic impact
Such estimates do not take into account that antimicrobials are integral to modern healthcare
We may not ever be able to make an accurate forecast of the costs
We should view greater investment in antibiotic resistance as an insurance policy
a rapid review, and interaction with colleagues who commissioned this
review at the Department of Health. Both authors contributed equally
to the writing of the paper. RS is guarantor.
Competing interests: We have read and understood the BMJ Group
policy on declaration of interests and have no relevant interests to
declare.
Provenance and peer review: Not commissioned; externally peer
reviewed.
1 Courvalin P. Predictable and unpredictable evolution of antibiotic resistance. J Intern Med
2008;264:4-16.
2 So AD, Ruiz-Esparza Q, Gupta N, Cars O. 3Rs for innovating novel antibiotics: sharing
resources, risks, and rewards. BMJ 2012:344:e1782.
3 Cormican M, Vellinga A. Existing classes of antibiotics are probably the best we will ever
have. BMJ 2012;344:e3369.
4 World Health Organization. The evolving threat of antimicrobial resistance: options for
action. WHO, 2012.
5 Coast J, Smith RD, Millar MR. Disentangling value: assessing the benefits of containing
antimicrobial resistance. In: Roberts J, ed. The economics of infectious disease. Oxford
University Press, 2006:201-14.
6 Smith RD, Coast J, Millar MR, Wilton P, Karcher A-M. Interventions against anti-microbial
resistance: a review of the literature and exploration of modelling cost-effectiveness.
WHO, 2001
7 Wilton P, Smith RD, Coast J, Millar M. Strategies to contain the emergence of antimicrobial
resistance: a systematic review of effectiveness and cost-effectiveness. J Health Serv
Res Policy 2002;7:111-7.
8 Smith R, Coast J. The economic burden of antimicrobial resistance. Why it is more serious
than current studies suggest. 2013. www.lshtm.ac.uk/php/economics/assets/dh_amr_
report.pdf.
9 Coast J, Smith RD, Karcher AM, Wilton P, Millar M. Superbugs II: how should economic
evaluation be conducted for interventions which aim to reduce antimicrobial resistance?
Health Econ 2002;11:637-7.
10 Gregor M. Bird flu: a virus of our own hatching. New York, 2006:85.
11 Cars O, Hogberg LD, Murray M, Jasper W, Nordberg O, Sivaraman S, et al. Meeting the
challenge of antibiotic resistance. BMJ 2008;337:726-8.
12 Bratzer DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from
the National Surgical Infection Prevention Project. Clin Infect Dis 2004;38:1706-15.
13 Wild SM. Antibiotic prophylaxis at caesarean section. Lancet 2002;360:724.
14 Plowman RP, Graves N, Griffin M, Roberts JA, Swan AV, Cookson BC, et al. The
socioecomic burden of hospital acquired infection. Public Health Laboratory Service,
1999.
15 Kanerva M, Blom M, Tuominen U, Kolho E, Anttila VJ, Vaara M, et al. Costs of an outbreak
of methicillin-resistant Staphylococcus aureus. Hosp Infect 2007;66:22-8.
Cite this as: BMJ 2013;346:f1493
© BMJ Publishing Group Ltd 2013
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BMJ 2013;346:f1493 doi: 10.1136/bmj.f1493 (Published 11 March 2013) Page 3 of 5
ANALYSIS

Table
Table 1| Annual cost of illness for selected conditions in US
Societal cost ($bn, 2004)Health problem
380Cardiovascular disease
w1
300Musculoskeletal conditions
w2
270Motor vehicle accidents
w3
266Occupational injury and illness
w4
260Mental disorders
w5
195Substance abuse
w6
185Cancer (all)
w7
145Diabetes
w8
70Alzheimer’s disease
w9
55Antimicrobial resistance
w10
48Skin disease
w11
23Urinary incontinence
w12
16Asthma
w13
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BMJ 2013;346:f1493 doi: 10.1136/bmj.f1493 (Published 11 March 2013) Page 4 of 5
ANALYSIS

Figure
Care pathway for total hip arthroplasty with and without antimicrobials
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BMJ 2013;346:f1493 doi: 10.1136/bmj.f1493 (Published 11 March 2013) Page 5 of 5
ANALYSIS
Citations
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TL;DR: The global situation of antibiotic resistance, its major causes and consequences, and key areas in which action is urgently needed are described and identified.
Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

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Abstract: Antimicrobial resistance is a global public health challenge, which has accelerated by the overuse of antibiotics worldwide. Increased antimicrobial resistance is the cause of severe infections, complications, longer hospital stays and increased mortality. Overprescribing of antibiotics is associated with an increased risk of adverse effects, more frequent re-attendance and increased medicalization of self-limiting conditions. Antibiotic overprescribing is a particular problem in primary care, where viruses cause most infections. About 90% of all antibiotic prescriptions are issued by general practitioners, and respiratory tract infections are the leading reason for prescribing. Multifaceted interventions to reduce overuse of antibiotics have been found to be effective and better than single initiatives. Interventions should encompass the enforcement of the policy of prohibiting the over-the-counter sale of antibiotics, the use of antimicrobial stewardship programmes, the active participation of clinicians in audits, the utilization of valid rapid point-of-care tests, the promotion of delayed antibiotic prescribing strategies, the enhancement of communication skills with patients with the aid of information brochures and the performance of more pragmatic studies in primary care with outcomes that are of clinicians’ interest, such as complications and clinical outcomes.

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Cites background from "The true cost of antimicrobial resi..."

  • ...A recent review demonstrated that the additional cost of resistance could be of £20,000 per patient episode in hospital [Smith and Coast, 2013]....

    [...]

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TL;DR: If the authors' overuse and misuse of antibiotics is not halted now, about 10 million people will die annually from drug-resistant bacterial infections within 35 years, and the world’s economy will lose more than 7% of its gross domestic product by 2050.
Abstract: If our overuse and misuse of antibiotics is not halted now, about 10 million people will die annually from drug-resistant bacterial infections within 35 years. The hammer blow will fall hardest on Africa and Asia, accounting for 4.1 and 4.7 million deaths, respec tively, and the world’s economy will lose more than 7% of its gross domestic product (USD210 trillion) by 2050. These numbers should make people sit up, listen and change behaviour.

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Abstract: Antimicrobial resistance (AMR) became in the last two decades a global threat to public health systems in the world. Since the antibiotic era, with the discovery of the first antibiotics that provided consistent health benefits to human medicine, the misuse and abuse of antimicrobials in veterinary and human medicine have accelerated the growing worldwide phenomenon of AMR. This article presents an extensive overview of the epidemiology of AMR, with a focus on the link between food producing-animals and humans and on the legal framework and policies currently implemented at the EU level and globally. The ways of responding to the AMR challenges foresee an array of measures that include: designing more effective preventive measures at farm level to reduce the use of antimicrobials; development of novel antimicrobials; strengthening of AMR surveillance system in animal and human populations; better knowledge of the ecology of resistant bacteria and resistant genes; increased awareness of stakeholders on the prudent use of antibiotics in animal productions and clinical arena; and the public health and environmental consequences of AMR. Based on the global nature of AMR and considering that bacterial resistance does not recognize barriers and can spread to people and the environment, the article ends with specific recommendations structured around a holistic approach and targeted to different stakeholders.

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Cites background from "The true cost of antimicrobial resi..."

  • ...In the USA the annual societal cost-of-illness for AMR is considered to be roughly $55 billion (Smith and Coast, 2013) with a clinical impact higher than HIV infection (Roberts et al., 2009)....

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  • ...In the USA the annual societal cost-of-illness for AMR is considered to be roughly $55 billion (Smith and Coast, 2013) with a clinical impact higher than HIV infection (Roberts et al....

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References
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TL;DR: This advisory statement provides an overview of other issues related to antimicrobial prophylaxis including specific suggestions regarding antimicrobial selection.
Abstract: In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup meeting The objectives were to review areas of agreement among the published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed The participants included authors from most of the published North American guidelines for antimicrobial prophylaxis and several specialty colleges The workgroup reviewed currently published guidelines for antimicrobial prophylaxis Nominal group process was used to draft a consensus paper that was widely circulated for comment The consensus positions of the workgroup include that infusion of the first antimicrobial dose should begin within 60 minutes before surgical incision and that prophylactic antimicrobial agents should be discontinued within 24 hours of the end of surgery This advisory statement provides an overview of other issues related to antimicrobial prophylaxis including specific suggestions regarding antimicrobial selection

1,180 citations

Journal ArticleDOI
TL;DR: This advisory statement provides an overview of other issues related to antimicrobial prophylaxis, including specific suggestions regarding antimicrobial selection.
Abstract: In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW) meeting. The objectives were to review areas of agreement among the most-recently published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed. The participants included authors from most of the groups that have published North American guidelines for antimicrobial prophylaxis, as well as authors from several specialty colleges. Nominal group process was used to draft a consensus paper that was widely circulated for comment. The consensus positions of SIPGWW include that infusion of the first antimicrobial dose should begin within 60 min before surgical incision and that prophylactic antimicrobials should be discontinued within 24 h after the end of surgery. This advisory statement provides an overview of other issues related to antimicrobial prophylaxis, including specific suggestions regarding antimicrobial selection.

811 citations

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TL;DR: One in three adults aged over 65 in England have difficulty understanding basic health‐related information, suggests a study in the BMJ, and the Patients Association said patients should help draft information leaflets so they are "relevant and clear".
Abstract: One in three adults aged over 65 in England have difficulty understanding basic health‐related information, suggests a study in the BMJ. They are more than twice as likely to die within five years as adults with no literacy problems, it was found. The University College London study tested nearly 8,000 adults on their understanding of aspirin instructions. The Patients Association said patients should help draft information leaflets so they are \"relevant and clear\". BMJ The Royal College of Nursing (RCN) has published 'Persistent challenges to providing quality care: An RCN report on the views and experiences of frontline nursing staff in care homes in England'. The report found that care homes are struggling to provide high quality care for residents with complex medical conditions, against a backdrop of a severe funding, equipment and staff shortages. The report identifies a lack of training for staff, inappropriate admissions and extreme pressure on the workforce leading to poor staff morale. The RCN says that getting health and social funding right is crucial for the sustainability of the social care system and the NHS. NHS Improvement have published 'Accurate diagnosis for suspected COPD'. This document covers diagnosis, tests and assessment of severity and impact. Through an early and quality assured diagnosis, a more comprehensive assessment of severity, effective proactive disease management and evidence based treatment interventions, lives will be saved and the burden on the resources of the NHS will be reduced. The webpages include information about a good patient pathway, evidence, guidance, top tips, service models, case studies etc

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18 Sep 2008-BMJ
TL;DR: A concerted global response is needed to tackle rising rates of antibiotic resistance, say Otto Cars and colleagues.
Abstract: A concerted global response is needed to tackle rising rates of antibiotic resistance, say Otto Cars and colleagues

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TL;DR: The predictable future of the relationship between bacteria and antibiotics is considered and resistance to antibiotics can result from mutations in resident structural or regulatory genes or from horizontal acquisition of foreign genetic information.
Abstract: Evolution of bacteria towards antibiotic resistance is unavoidable as it represents a particular aspect of the general evolution of bacteria. Thus, at the very best, the only hope we can have in the field of resistance is to delay dissemination of resistant bacteria or resistance genes. Resistance to antibiotics in bacteria can result from mutations in resident structural or regulatory genes or from horizontal acquisition of foreign genetic information. In this review, we will consider the predictable future of the relationship between bacteria and antibiotics.

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Related Papers (5)
Frequently Asked Questions (2)
Q1. What are the contributions in "The true cost of antimicrobial resistance" ?

In this paper, the authors argue that antibiotic resistance has fallen victim to evidence-based policy making, which prioritises health problems by economic burden and cost effectiveness of interventions. 

Although the authors now have more empirical information on the economic burden of resistance than was available a decade ago, it is unlikely to help us plan for the future. And the authors have explained how resistance has the potential to undermine modern health systems. Full health systems analyses seem a more appropriate means to assess the potential impact of resistance and evaluate measures to stem it. An increase in resistant organisms coupled with a big fall in the number of new antimicrobial drugs suggests an apocalyptic scenario may be looming Current estimates suggest antimicrobial resistance has a low economic impact Such estimates do not take into account that antimicrobials are integral to modern healthcare