TEDMED 2014

Ramanan Laxminarayan: The coming crisis in antibiotics

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Antibiotic drugs save lives. But we simply use them too much — and often for non-lifesaving purposes, like treating the flu and even raising cheaper chickens. The result, says researcher Ramanan Laxminarayan, is that the drugs will stop working for everyone, as the bacteria they target grow more and more resistant. He calls on all of us (patients and doctors alike) to think of antibiotics -- and their ongoing effectiveness -- as a finite resource, and to think twice before we tap into it. It’s a sobering look at how global medical trends can strike home.

- Drug-resistance economist
At the Center for Disease Dynamics, Economics & Policy, economist Ramanan Laxminarayan looks at big-picture issues of global health. Full bio

The first patient to ever be
treated with an antibiotic
00:12
was a policeman in Oxford.
00:16
On his day off from work,
00:17
he was scratched by a rose thorn
while working in the garden.
00:19
That small scratch became infected.
00:23
Over the next few days,
his head was swollen
00:26
with abscesses,
00:29
and in fact his eye was so infected
00:30
that they had to take it out,
00:33
and by February of 1941,
00:35
this poor man was on the verge of dying.
00:38
He was at Radcliffe Infirmary in Oxford,
00:40
and fortunately for him,
00:43
a small team of doctors
00:45
led by a Dr. Howard Florey
00:47
had managed to synthesize
00:48
a very small amount of penicillin,
00:50
a drug that had been discovered
00:53
12 years before by Alexander Fleming
00:55
but had never actually been
used to treat a human,
00:58
and indeed no one even
knew if the drug would work,
01:01
if it was full of impurities
that would kill the patient,
01:04
but Florey and his team figured
01:07
if they had to use it,
they might as well use it
01:09
on someone who was going to die anyway.
01:11
So they gave Albert Alexander,
01:14
this Oxford policeman, the drug,
01:17
and within 24 hours,
01:20
he started getting better.
01:23
His fever went down,
his appetite came back.
01:25
Second day, he was doing much better.
01:29
They were starting to
run out of penicillin,
01:31
so what they would do
was run with his urine
01:33
across the road to re-synthesize
the penicillin from his urine
01:35
and give it back to him,
01:38
and that worked.
01:40
Day four, well on the way to recovery.
01:42
This was a miracle.
01:44
Day five, they ran out of penicillin,
01:46
and the poor man died.
01:50
So that story didn't end that well,
01:52
but fortunately for
millions of other people,
01:55
like this child who was treated
again in the early 1940s,
01:59
who was again dying of a sepsis,
02:02
and within just six days, you can see,
02:05
recovered thanks to this
wonder drug, penicillin.
02:08
Millions have lived,
02:12
and global health has been transformed.
02:14
Now, antibiotics have been used
02:17
for patients like this,
02:20
but they've also been
used rather frivolously
02:23
in some instances,
02:25
for treating someone
with just a cold or the flu,
02:27
which they might not have
responded to an antibiotic,
02:29
and they've also been
used in large quantities
02:32
sub-therapeutically, which
means in small concentrations,
02:36
to make chicken and hogs grow faster.
02:39
Just to save a few pennies
on the price of meat,
02:42
we've spent a lot of
antibiotics on animals,
02:46
not for treatment, not for sick animals,
02:49
but primarily for growth promotion.
02:51
Now, what did that lead us to?
02:54
Basically, the massive use of antibiotics
02:57
around the world
03:00
has imposed such large
selection pressure on bacteria
03:01
that resistance is now a problem,
03:05
because we've now selected for just
03:08
the resistant bacteria.
03:10
And I'm sure you've all read
about this in the newspapers,
03:11
you've seen this in every magazine
03:14
that you come across,
03:16
but I really want you to appreciate
03:18
the significance of this problem.
03:20
This is serious.
03:22
The next slide I'm about to show you is
of carbapenem resistance in acinetobacter.
03:23
Acinetobacter is a nasty hospital bug,
03:28
and carbapenem is pretty much
03:31
the strongest class of antibiotics
03:32
that we can throw at this bug.
03:34
And you can see in 1999
03:36
this is the pattern of resistance,
03:39
mostly under about 10 percent
across the United States.
03:42
Now watch what happens
when we play the video.
03:45
So I don't know where you live,
03:58
but wherever it is, it certainly is a lot worse now
04:00
than it was in 1999,
04:03
and that is the problem of antibiotic resistance.
04:05
It's a global issue
04:09
affecting both rich and poor countries,
04:11
and at the heart of it,
you might say, well,
04:14
isn't this really just a medical issue?
04:16
If we taught doctors how not
to use antibiotics as much,
04:18
if we taught patients how
not to demand antibiotics,
04:20
perhaps this really wouldn't be an issue,
04:23
and maybe the pharmaceutical companies
04:25
should be working harder to develop
04:27
more antibiotics.
04:28
Now, it turns out that there's something
fundamental about antibiotics
04:30
which makes it different from other drugs,
04:33
which is that if I misuse antibiotics
04:35
or I use antibiotics,
04:37
not only am I affected but
others are affected as well,
04:39
in the same way as if I
choose to drive to work
04:43
or take a plane to go somewhere,
04:45
that the costs I impose on others
04:48
through global climate change go everywhere,
04:50
and I don't necessarily take
these costs into consideration.
04:52
This is what economists might
call a problem of the commons,
04:55
and the problem of the commons is exactly
04:58
what we face in the case
of antibiotics as well:
05:00
that we don't consider —
05:02
and we, including individuals, patients,
05:04
hospitals, entire health systems —
05:07
do not consider the costs
that they impose on others
05:11
by the way antibiotics are actually used.
05:13
Now, that's a problem that's similar
05:15
to another area that we all know about,
05:17
which is of fuel use and energy,
05:19
and of course energy use
05:21
both depletes energy as well as
05:23
leads to local pollution
and climate change.
05:26
And typically, in the case of energy,
05:29
there are two ways in which
you can deal with the problem.
05:31
One is, we can make better
use of the oil that we have,
05:33
and that's analogous to making better use
05:37
of existing antibiotics,
05:39
and we can do this in a number of ways
05:41
that we'll talk about in a second,
05:42
but the other option is the
"drill, baby, drill" option,
05:45
which in the case of antibiotics
is to go find new antibiotics.
05:48
Now, these are not separate.
05:53
They're related, because if we invest heavily
05:55
in new oil wells,
05:58
we reduce the incentives
for conservation of oil
06:00
in the same way that's going
to happen for antibiotics.
06:03
The reverse is also going
to happen, which is that
06:06
if we use our antibiotics appropriately,
06:08
we don't necessarily have
to make the investments
06:10
in new drug development.
06:13
And if you thought that these two were entirely,
06:15
fully balanced between these two options,
06:18
you might consider the fact that
06:20
this is really a game that we're playing.
06:22
The game is really one of coevolution,
06:24
and coevolution is, in
this particular picture,
06:27
between cheetahs and gazelles.
06:30
Cheetahs have evolved to run faster,
06:32
because if they didn't run faster,
06:34
they wouldn't get any lunch.
06:35
Gazelles have evolved to run faster because
06:37
if they don't run faster, they would be lunch.
06:40
Now, this is the game we're
playing against the bacteria,
06:43
except we're not the cheetahs,
06:46
we're the gazelles,
06:48
and the bacteria would,
06:49
just in the course of this little talk,
06:52
would have had kids and grandkids
06:54
and figured out how to be resistant
06:55
just by selection and trial and error,
06:58
trying it over and over again.
07:00
Whereas how do we stay
ahead of the bacteria?
07:02
We have drug discovery processes,
07:06
screening molecules,
07:08
we have clinical trials,
07:10
and then, when we think we have a drug,
07:11
then we have the FDA regulatory process.
07:14
And once we go through all of that,
07:17
then we try to stay one step ahead
07:20
of the bacteria.
07:22
Now, this is clearly not a
game that can be sustained,
07:24
or one that we can win
07:27
by simply innovating to stay ahead.
07:28
We've got to slow the pace of coevolution down,
07:30
and there are ideas that we
can borrow from energy
07:33
that are helpful in thinking about
07:37
how we might want to do this in the case
07:39
of antibiotics as well.
07:40
Now, if you think about how we deal with
07:42
energy pricing, for instance,
07:44
we consider emissions taxes,
07:45
which means we're imposing
the costs of pollution
07:47
on people who actually use that energy.
07:50
We might consider doing that for antibiotics as well,
07:53
and perhaps that would make sure that antibiotics
07:56
actually get used appropriately.
07:58
There are clean energy subsidies,
08:01
which are to switch to fuels
which don't pollute as much
08:03
or perhaps don't need fossil fuels.
08:06
Now, the analogy here is, perhaps we need
08:09
to move away from using antibiotics,
08:11
and if you think about it, what are
good substitutes for antibiotics?
08:14
Well, turns out that anything that reduces
08:17
the need for the antibiotic would really work,
08:20
so that could include improving
hospital infection control
08:22
or vaccinating people,
08:25
particularly against
the seasonal influenza.
08:28
And the seasonal flu is probably
08:30
the biggest driver of antibiotic use,
08:33
both in this country as well
as in many other countries,
08:36
and that could really help.
08:39
A third option might include
something like tradeable permits.
08:41
And these seem like faraway scenarios,
08:45
but if you consider the
fact that we might not
08:49
have antibiotics for many
people who have infections,
08:51
we might consider the fact that we might
08:55
want to allocate who actually gets to use
08:57
some of these antibiotics over others,
08:59
and some of these might have to
be on the basis of clinical need,
09:02
but also on the basis of pricing.
09:05
And certainly consumer education works.
09:07
Very often, people overuse antibiotics
09:09
or prescribe too much without necessarily
09:12
knowing that they do so,
09:14
and feedback mechanisms
09:16
have been found to be useful,
09:17
both on energy —
09:19
When you tell someone that they're using
09:21
a lot of energy during peak hour,
09:23
they tend to cut back,
09:24
and the same sort of example has been performed
09:26
even in the case of antibiotics.
09:28
A hospital in St. Louis basically would put up
09:29
on a chart the names of surgeons
09:31
in the ordering of how much antibiotics they'd used
09:36
in the previous month,
09:38
and this was purely an
informational feedback,
09:40
there was no shaming,
09:42
but essentially that provided
some information back
09:43
to surgeons that maybe they could rethink
09:45
how they were using antibiotics.
09:47
Now, there's a lot that can be done
09:50
on the supply side as well.
09:52
If you look at the price of penicillin,
09:54
the cost per day is about 10 cents.
09:56
It's a fairly cheap drug.
09:57
If you take drugs that have
been introduced since then —
09:59
linezolid or daptomycin —
10:01
those are significantly more expensive,
10:04
so to a world that has been used to
paying 10 cents a day for antibiotics,
10:06
the idea of paying 180 dollars per day
10:11
seems like a lot.
10:14
But what is that really telling us?
10:15
That price is telling us
10:17
that we should no longer
10:19
take cheap, effective
antibiotics as a given
10:21
into the foreseeable future,
10:25
and that price is a signal to us
10:27
that perhaps we need to be paying
10:29
much more attention to conservation.
10:31
That price is also a signal
10:34
that maybe we need to start
looking at other technologies,
10:36
in the same way that
gasoline prices are a signal
10:39
and an impetus, to, say,
10:42
the development of electric cars.
10:44
Prices are important signals
10:46
and we need to pay attention,
10:48
but we also need to consider the fact that
10:50
although these high prices
seem unusual for antibiotics,
10:52
they're nothing compared to the price per day
10:56
of some cancer drugs,
10:59
which might save a patient's life only
for a few months or perhaps a year,
11:00
whereas antibiotics would potentially
11:03
save a patient's life forever.
11:05
So this is going to involve
11:07
a whole new paradigm shift,
11:08
and it's also a scary shift because
11:10
in many parts of this country,
11:12
in many parts of the world,
11:14
the idea of paying 200 dollars
11:16
for a day of antibiotic treatment
11:18
is simply unimaginable.
11:21
So we need to think about that.
11:24
Now, there are backstop options,
11:25
which is other alternative technologies
11:27
that people are working on.
11:30
It includes bacteriophages, probiotics,
11:31
quorum sensing, synbiotics.
11:34
Now, all of these are useful avenues to pursue,
11:38
and they will become even more lucrative
11:41
when the price of new
antibiotics starts going higher,
11:43
and we've seen that the
market does actually respond,
11:47
and the government is now considering
11:49
ways of subsidizing new
antibiotics and development.
11:51
But there are challenges here.
11:55
We don't want to just throw money at a problem.
11:57
What we want to be able to do
11:59
is invest in new antibiotics
12:00
in ways that actually encourage
12:02
appropriate use and sales of those antibiotics,
12:05
and that really is the challenge here.
12:08
Now, going back to these technologies,
12:11
you all remember the line from that famous
12:13
dinosaur film, "Nature will find a way."
12:15
So it's not as if these are
permanent solutions.
12:18
We really have to remember that,
whatever the technology might be,
12:21
that nature will find some
way to work around it.
12:25
You might think, well,
this is just a problem
12:28
just with antibiotics and with bacteria,
12:30
but it turns out that we
have the exact same
12:33
identical problem in
many other fields as well,
12:35
with multidrug-resistant tuberculosis,
12:37
which is a serious problem
in India and South Africa.
12:40
Thousands of patients are dying because
12:44
the second-line drugs are so expensive,
12:46
and in some instances, even those don't work
12:48
and you have XDR TB.
12:50
Viruses are becoming resistant.
12:52
Agricultural pests. Malaria parasites.
12:54
Right now, much of the world depends on
12:57
one drug, artemisinin drugs,
12:59
essentially to treat malaria.
13:02
Resistance to artemisinin has already emerged,
13:04
and if this were to become widespread,
13:07
that puts at risk
13:09
the single drug that we have to
treat malaria around the world
13:11
in a way that's currently
safe and efficacious.
13:14
Mosquitos develop resistance.
13:17
If you have kids, you probably
know about head lice,
13:19
and if you're from New York City,
13:21
I understand that the
specialty there is bedbugs.
13:22
So those are also resistant.
13:25
And we have to bring an
example from across the pond.
13:27
Turns out that rats are
also resistant to poisons.
13:30
Now, what's common
to all of these things is
13:33
the idea that we've had these technologies
13:35
to control nature only for
the last 70, 80 or 100 years
13:38
and essentially in a blink,
13:43
we have squandered our ability to control,
13:46
because we have not recognized
13:48
that natural selection and
evolution was going to find
13:51
a way to get back,
13:54
and we need to completely rethink
13:55
how we're going to use
13:57
measures to control biological organisms,
13:59
and rethink how we incentivize
14:02
the development, introduction,
14:06
in the case of antibiotics prescription,
14:08
and use of these valuable resources.
14:11
And we really now need to
start thinking about them
14:14
as natural resources.
14:17
And so we stand at a crossroads.
14:19
An option is to go through that rethinking
14:21
and carefully consider incentives
14:24
to change how we do business.
14:26
The alternative is
14:28
a world in which even a blade of grass
14:31
is a potentially lethal weapon.
14:34
Thank you.
14:36
(Applause)
14:38

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About the Speaker:

Ramanan Laxminarayan - Drug-resistance economist
At the Center for Disease Dynamics, Economics & Policy, economist Ramanan Laxminarayan looks at big-picture issues of global health.

Why you should listen

Economist Ramanan Laxminarayan works to improve understanding of drug resistance as a problem of managing a shared global resource. As Director and Senior Fellow at the Center for Disease Dynamics, Economics & Policy (CDDEP), he is interested in cross-disciplinary, pragmatic solutions to reduce drug resistance. He has advised the World Health Organization and World Bank on evaluating malaria treatment policy, vaccination strategies, the economic burden of tuberculosis, and control of non-communicable diseases. He was a key architect of the Affordable Medicines Facility for malaria, a novel financing mechanism to improve access and delay resistance to antimalarial drugs. In 2012, he created the Immunization Technical Support Unit in India, which has been credited with improving the immunization program in the country. He teaches at Princeton.

As he says: "It has been a long time since people died of untreatable bacterial infections, and the prospect of returning to that world is worrying."