[Ip-health] Mark Woolhouse& Jeremy Farrar in Nature - Policy: An intergovernmental panel on antimicrobial resistance

Thiru Balasubramaniam thiru at keionline.org
Wed May 28 04:16:06 PDT 2014



Policy: An intergovernmental panel on antimicrobial resistance

   - Mark Woolhouse<http://www.nature.com/news/policy-an-intergovernmental-panel-on-antimicrobial-resistance-1.15275#auth-1>
   - & Jeremy Farrar<http://www.nature.com/news/policy-an-intergovernmental-panel-on-antimicrobial-resistance-1.15275#auth-2>

22 May 2014

Drug-resistant microbes are spreading. A coordinated, global effort is
needed to keep drugs working and develop alternatives, say Mark Woolhouse
and Jeremy Farrar.

Last month, the World Health Organization (WHO) produced a global
antimicrobial resistance, warning that a ‘post-antibiotic’ world could soon
become a reality. In some ways, it already has.

Drugs that were once lifesavers are now worthless. Chloramphenicol, once a
physician’s first choice against typhoid, is no longer effective in many
parts of the world. Strains of extensively drug-resistant tuberculosis
(TB), methicillin-resistant* Staphylococcus aureus *(MRSA),
multidrug-resistant *Escherichia coli* and *Klebsiella**pneumoniae* are
serious threats to public health. *Plasmodium falciparum* (the parasite
that causes the most dangerous form of malaria) is developing resistance to
all known classes of anti­malarial drug, threatening the remarkable
progress that has been made against the disease. HIV is increasingly
resistant to first-line antiviral drugs. Every class of antibiotic is
increasingly compromised by resistance, as are many antivirals,
antiparasitic and antifungal drugs.

It could get worse: routine medical care, surgery, cancer treatment, organ
transplants and industrialized agriculture would be impossible in their
present form without antimicrobials. And the treatment of many infectious
human and livestock diseases now relies on just one or two drugs.

Resistance has spread around the world. MRSA has spread between
as have resistant strains of TB, malaria, HIV and pneumococci. Genes
conferring resistance to β-lactams — antibiotics used against a broad range
of infections, including *E. coli* and *K. pneumoniae* — have spread to
bacterial populations worldwide, probably originating in the Indian
Numerous drug-resistant malaria strains have spread from southeast Asia to

Antimicrobial resistance is a global problem that requires global
, 4<http://www.nature.com/news/policy-an-intergovernmental-panel-on-antimicrobial-resistance-1.15275#b4>.
So far, the international response has been feeble. The WHO accepted only
last month that antimicrobial resistance might fall within the remit of the
International Health
which were implemented in 2007 to deal with events such as influenza
pandemics. The regulations’ extension to antimicrobial resistance would
oblige the 196 signatory countries to carry out effective surveillance and
timely reporting for outbreaks of resistance.


What is required is committed and coordinated action on the root causes of
resistance: the misuse of antimicrobials, the paucity of development of new
drugs and the lack of alternatives. Guidelines must be implemented to
improve the use of existing drugs; the scientific and business worlds need
incentives and a better regulatory environment to develop new drugs and
approaches, and those working in both the animal and human sectors need
education and incentives to help them to change their ways.

We call for the creation of an organization similar to the
Intergovernmental Panel on Climate Change (IPCC) to marshal evidence and
catalyse policy across governments and stakeholders.
Use and misuse

Although all kinds of microbes evolve resistance, resistant bacteria are
currently the greatest cause for concern.It is no coincidence that the
nations with the strictest policies on antibiotic prescription
(Scandinavian countries and the Netherlands) have the lowest rates of
resistance. But in most of the developed world, clinical use of antibiotics
has not declined, despite frequent calls to curtail overuse. In developing
countries with rising incomes, consumption is surging; sales of even
relatively expensive antibiotics increased fivefold in India and tripled in
Egypt in 2005–10 (see ‘A market for
This growth is fuelled by unregulated, over-the-counter sales of
antimicrobials of all kinds.

In the United States, antibiotic usage in humans is matched by that in farm
animals, mainly as growth promoters. The European Union banned the use of
antibiotics as growth promoters in animals in 2006, but the situation is
little better. As industrialized agriculture expands, notably in Asia,
animal antibiotic usage will continue to grow.

Mitigating resistance will require coordination across sectors. Physicians,
pharmacists, veterinarians, patients and farmers all contribute to the
overuse of antimicrobials. All have a part to play in using them more
intelligently. However, changing practices in the hospital, clinic or farm
is not easy. The onus is on countries that are major producers and
consumers of antimicrobials — especially the United States and European
nations, and increasingly India and China — to introduce policies that
promote best practice.

Currently, national efforts are patchy and disconnected. The United Kingdom
last year published a five-year strategic plan to combat resistance (see
go.nature.com/ideq6t), although with no new money attached. Vietnam aims to
combat resistance through its VINARES
but most countries have no such programmes. The United States is still
debating how to reduce the use of growth promoters in animals. Regional
initiatives such as the European Antimicrobial Resistance Surveillance
Network are yet to be replicated elsewhere. Controls that do exist are
often weakly implemented or are no more than voluntary guidelines.
Resistance is natural

Most of the antibiotics in use today, from penicillin to carbapenems,
originated in soil. Long before they were used as medicines, soil microbes
were producing antibiotics, and bacteria were evolving resistance to these
natural compounds. This has been happening for perhaps billions of
a massive scale: there are at least 50 tonnes of bacteria for every person
on the planet7<http://www.nature.com/news/policy-an-intergovernmental-panel-on-antimicrobial-resistance-1.15275#b7>

Humans became involved with the manufacture of antibiotics on an industrial
scale only in the 1940s. Today, 20 tonnes of antibiotics are produced every
hour, contributing to a global industry that is worth more than
US$30 billion a year. We are now in a race against evolution; new
antimicrobials are deployed and, often within a few years, resistance
develops. Factory-produced antibiotics are presenting bacteria with a type
of chemical attack that they have overcome many times before.

Between 1983 and 1992, 30 new antibiotics were approved by the US Food and
Drug Administration. From 2003 to 2012, the number was just seven. Why?
Because there are too few incentives and too many regulatory barriers for
the commercial sector to invest what is needed for the development of new
Drug development is risky, and antibiotics do not generate as much revenue
as drugs for chronic conditions do. Drug companies find that research in
other diseases is a better return on investment.
A global approach

In many ways, antimicrobial resistance is similar to climate change. Both
are processes operating on a global scale for which humans are largely
responsible. In anti­microbial resistance, as in climate change, the
practices of one country affect many others.

One key difference is that, for climate change, technologies exist to
produce energy without burning fossil fuels, and investments and incentives
will make them practical and affordable. Alternatives to antimicrobials —
such as probiotics, prebiotics or phage therapy — are still, at best,
More research on alternatives is urgently needed, coupled with efforts by
industry, academia and governments to market them in a scalable way.

There have also already been internationally agreed, evidence-based targets
for cutting carbon dioxide emissions. There are no global targets for
reducing antimicrobial use and no real understanding of how to set them. We
do not even know what, if any, level of antimicrobial usage will be
sustainable in the long term.

The threat of anthropogenic climate change led to the creation in 1988 of
the IPCC. Despite its limitations, the panel is arguably the most
successful attempt in history to empower scientific consensus to inform
global policy and practice.

Another useful precedent is the Montreal Protocol on Substances that
Deplete the Ozone Layer, the first universally ratified treaty in the
history of the United Nations. Faced with clear data that the ozone layer,
which protects Earth from ultraviolet radiation, was under threat,
governments agreed on a timetable to phase out ozone-depleting chemicals.
The protocol, which came into force in 1989, is considered the most
successful global environmental treaty, and has led to the shrinking of the
ozone hole.

We believe that similar global approaches should be attempted to address
problems in public health. There is a need for a powerful panel to marshal
the data to inform and encourage implementation of policies that will
forestall the loss of effective drugs to resistance, and to promote and
facilitate the development of alternatives — a panel akin to the IPCC, and
the analogous Intergovernmental Science-Policy Platform on Biodiversity and
Ecosystem Services founded in 2012. An intergovernmental panel on
antimicrobial resistance (IPAMR) must have the same firm foundation on the
best available science and potentially an even stronger mandate for action.

>From the outset, the IPAMR needs to avoid simply restating the problem. It
must move rapidly to an agenda that includes identifying key knowledge gaps
and how to fill them; assessing viable short- and long-term solutions;
evaluating barriers to implementation; and setting out road maps for
sustainable control of disease-causing microbes. It could, for example,
support studies to investigate dosing regimes that stall resistance,
coordinate incentives for developing new types of antimicrobial and set
targets for prescriptions and animal use.

To have any chance of achieving these objectives, the IPAMR must be trusted
and free of vested interests. It will need to involve a broad range of
experts, encompassing clinical and veterinary medicine, epidemiology,
microbiology, pharmacology, health economics, international law and social
science. It will need technical, financial, industrial and political
support from governments and agencies including the WHO, the World
Organisation for Animal Health, the World Trade Organization and the United
Nations, as well as from representatives of producers and consumers of
antimicrobial drugs. Above all, it will need strong, independent leadership.

Creating an effective IPAMR will be a huge undertaking, but the successful
global campaign to eradicate smallpox, led by the WHO, demonstrates that a
coordinated, international response to a public-health threat can work. The
attempt must be made — otherwise, the massive health gains made possible by
antimicrobial drugs will be lost.
Nature 509, 555–557 (29 May 2014) doi:10.1038/509555a

   - See Editorial page 533<http://www.nature.com/uidfinder/10.1038/509533a>



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