
A 'slow catastrophe' unfolds as the golden age of antibiotics comes to an end - Mz
http://www.latimes.com/science/sciencenow/la-sci-antibiotic-resistance-20160711-snap-story.html
======
KaiserPro
So there are two issues that are touched on here, which are not really
expanded enough.

1) farmers everywhere are allowed to use last line/new antibiotics routinely
in food production. This is utterly fucking stupid. Whats more brain dead is
that its not just china its US and canada. (possibly the EU.) It could be
stopped by the FDA withdrawing the license. but no. Too much money.

2) over subscription in private health.

I once listened to a co-worker phone up the Doctor and ask to have "the same
antibiotics I had last time for that cold" and get it[1]. She had the fucking
snuffles. No consultation, not even bothering to figure out if its even got a
hint of bacterial infection.

A placebo would have been more effective. It wouldn't have given her the shits
either. Paracetamol is what was needed, as its the only thing that would have
made her feel better.

Seriously. yes I know that the customer is always right, but don't fucking
dish out drugs like sweets. My old age, and my children's health are dependent
on those drugs.

[1] yes this was in the USA, santa monica to be precise. Yes I'm british.
However the prevalence of prescription medication abuse and deaths is a
massive fucking warning. Something is horridly wrong with the US's health care
system.

What surprises me is with the levels of litigation against doctors, this
hasn't seemed to trigger any change in behaviour.

Disclosure: I live with a doctor.

~~~
stcredzero
_1) farmers everywhere are allowed to use last line /new antibiotics routinely
in food production. This is utterly fucking stupid._

Basically, it's exactly the worst thing you can possibly do, with regards to
what the theory of evolution by natural selection tells us. Then add in what
we know about bacteria exchanging genetic material, and it's like we're
_trying_ to inactivate all of our antibiotics on purpose.

~~~
trhway
>Basically, it's exactly the worst thing you can possibly do, with regards to
what the theory of evolution by natural selection tells us.

from the half-full glass POV we are just speeding up the natural selection of
bacteria resistant humans (it has been going for millenia and got, probably
only temporary, delayed for the last 80 years). Also, as a side effect, it can
help solve (at least temporarily) the overpopulation issue until the much more
smart (wrt. health and Earth resources usage) humans evolve. Basic dialectics
at work.

~~~
vacri
Having antibiotic failure as the method for arresting the massive human
population (7B people) would require carnage that makes World War II (~70M
deaths) pale in comparison, even if you correct for the lower global
population of the day.

~~~
dredmorbius
Disease has typically killed more than wars. The Spanish Flu epidemic of 1918
killed 50-100 million people, several percent of the total world population.
By comparison, total military and civilian dealths in WWI were about 16
million.

~~~
vacri
Oh, I agree - I just used WWII as it's a more commonly-understood datapoint.
The Spanish Flu epidemic only took a couple of years as well, as opposed to
the half-decade of WWII.

------
yourkin
Articles like this urge me to stop reading pop science journalism altogether.

What is not mentioned is a new class of antibiotics discovered in 2015
([https://en.wikipedia.org/wiki/Teixobactin](https://en.wikipedia.org/wiki/Teixobactin))
which is a big deal in that it can be used instead of antibiotics resistance
to which has been acquired by bacteria during this "golden age" and as
microbes evolve extremely fast, within an observable timeframe they will lose
resistance to the old classes allowing those to be used again. So effectively
shelving will work.

Another point is that other new methods of searching for new drugs are being
researched ([http://www.theverge.com/2016/5/18/11686268/new-antibiotic-
dr...](http://www.theverge.com/2016/5/18/11686268/new-antibiotic-drug-
candidates-resistance-harvard-macrolide)) and the future is not at all gloomy.

~~~
pak
Teixobactin is cool, but if it's only active against gram positives, it's
never going to work against most of the bacteria listed in the article: E.
coli, Salmonella, Klebsiella, N. gonorrhoeae, etc. Most of the terrible new
drug resistance genes are showing up in gram negatives.

Sure, new methods of finding antibiotics are in the works, although the
article you link has plenty of experts recommending caution about their
potential. The bigger point is that in 2016 there is a looooooong road from
antibiotic "candidate" to FDA-approved drug. That road involves decades of
trials and costs billions of dollars per approved drug.

The larger problem is that there is little if any incentive for pharma
companies to invest in antibiotics compared to traditional blockbuster drugs
that are supposed to be taken chronically (and therefore have better ROI).
It's the same reason little R&D goes into making new vaccines. It doesn't
matter how many candidates are found if they can't make it to market in a
timely fashion (the point of the CDC bar graph), and this is what the "slow
catastrophe" really is. It is not that scientists will never figure out new
ways to kill bacteria.

~~~
busyant
I used to work at an antibiotic discovery startup.

I used to joke that there were _so many_ groups with a Gram+ antibiotic drug
discovery program going that my parents were probably running one out of their
cellar.

Gram- are tough.

~~~
Fordrus
An antibiotic discovery startup, eh?

That's freaking fascinating, I'm in bioinformatics myself, I'd love to hear
more about this- I wasn't aware that an antibiotic discovery startup
was/is/could be a thing at all- If you can tell me anything more or put me on
the right track to reading more about your old employer in that space or
whatnot, I'd appreciate it! :)

~~~
busyant
I'd rather not mention my recent employer.

But these startups do exist: look up Achaogen (achaogen.com) and Tetraphase
(tphase.com).

Cubist Pharmaceuticals was a big antibiotic developer that was recently
purchased by Merck. Cubist itself bought another startup called Trius
Pharmaceuticals, which had developed a newly marketed antibiotic.

So, there _is_ $$ to be made in antibiotic drug development, but as many
people on this thread have pointed out, there is _more_ $$$$ to be made in
other therapeutic areas (e.g., oncology).

------
RcouF1uZ4gsC
This is to be expected. The big issue is that it is not worth it for a
pharmaceutical company to develop new antibiotics. The initial cost is high.
Then, if it is successful, the antibiotic will only be given as a last resort,
thus reducing the number of doses. In addition, unlike chronic conditions such
as diabetes or high blood pressure, severe bacterial infection is usually time
limited - the patient will either get better or they will die. In either case,
they do not continue to need the antibiotic. Thus, to recoup costs, the
pharmaceutical company will have to sell it at low volume/high prices. Of
course, if they do that, the press starts blaming them for the high cost of
the medication and it is a PR disaster (see Sovaldi) even though everyone is
strictly better off due to their selling the antibiotic even at a higher
price. In the end, it is better for their reputation and their bottom line not
to develop these antibiotics. Thus, mainly because we do not have aggressive
new development of antibiotics for these severe infections, we have these
articles claiming the end of the antibiotic age.

~~~
ansible
And in response to that, the pharmaceutical companies will sell the antibiotic
in high volumes to the livestock industry. Thus increasing profits... forever!

~~~
loup-vaillant
With the nice side effect that this will spur more resistances, hence more
reasons to develop new drugs, that they can sell at higher prices, driving
profits even upper.

It's nice to get paid to solve a problem you created in the first place.

------
notadoc
This is a public health crisis that needs urgent attention. Governments should
step in with huge funding to NIH and pharma to accelerate R&D, and offer
incentives to invest heavily in antibiotic development (extended patent terms
for antibiotics, tax-free repatriation for antibiotic R&D funds, whatever it
takes).

The current free market approach is completely failing this. It's not
particularly profitable to invest many years in a drug people only need to
take once to cure a disease when compared to developing a drug people need to
take for 5-10+ years to manage a disease.

Phage therapy should be further developed as well, which has been proven to
work against some resistant strains.

~~~
savanaly
>The current free market approach is completely failing this. It's not
particularly profitable to invest many years in a drug people only need to
take once to cure a disease when compared to developing a drug people need to
take for 5-10+ years to manage a disease.

Why couldn't their payment scheme be identical even if it's a one time dose?
Instead of $1000 per year for a drug you need to buy every year for ten years,
make it so it has an up front cost of $12,000 or whatever with a ten year
payment plan available for people who don't have that kind of cash on hand.
This suggestion obviously inspired by the real world good that is a one time
purchase that people make all the time: houses.

~~~
xg15
Martin Shkreli approves.

But to elaborate, aside from the obvious ethical implications, there are also
practical differences. You are usually not forced out-of-the-blue to buy a
house, no matter if you can afford it or have just bought a house last month.
Also, houses can be sold, so people have ways to back out of a purchase when
they realize they cannot pay back the loan. None of this works for drugs.

Trying to apply the same logic to drugs would make the the debt problem of
medical bills even worse than it already is. It would also lead to a strong
inequality in medical care.

~~~
savanaly
Isn't Martin Shkreli notorious for hiking prices on drugs, not for pioneering
new payment models for drugs? My post was about how if a company had a drug
which it had development cost $X for, it could recoup X + p from the consumer
_even if_ the drug is a one time dose rather than an ongoing treatment. How
much p profit they make is a separate question and anyways is sort of
orthogonal to the question of whether they pay per month or once.

------
carapace
Bacteriophage therapy?

[https://en.wikipedia.org/wiki/Phage_therapy](https://en.wikipedia.org/wiki/Phage_therapy)

~~~
abrookewood
I always wonder why this is never mentioned in these articles. If I recall
correctly, this approach is quite popular in Russia.

~~~
Fomite
There are considerable problems with it. It's popular in Russia because they
didn't have access to antibiotics in large quantities.

~~~
abrookewood
Can you elaborate on what the problems are? I haven't read much on it, but it
sounded very promising.

------
a3n
> The economics of drug development are partly to blame.

> To offset the millions of dollars they pour into research, clinical trials
> and the FDA approval process, pharmaceutical companies aim to develop
> blockbuster drugs, said Dr. Anthony Fauci, director of the National
> Institute for Allergies and Infectious Diseases. An ideal candidate would be
> used by millions of people every day for the rest of their lives, like pills
> to keep cholesterol or blood pressure in check.

> Antibiotics won’t pay the freight. They should be prescribed sparingly and
> only used for about a week.

Hmmm. Natural selection of humans, in an environment partly controlled by
Pharma.

Pharma needs lots of patients that consume a drug every day for life. (I take
three of them, plus an arguable fourth.) People who take one or more of these
drugs are valuable. Such people who live longer lives are more valuable.

By not discovering low revenue new antibiotics and making them available, what
we're left with is people who take daily drugs for life, and somehow survive
or avoid bacterial infection.

I want to believe that no one in Pharma has thought of this.

------
praptak
"Researchers haven’t identified a new class of antibiotic medication since
1987."

Teixobactin is 2015 and is probably a member of a new class of antibiotics.

~~~
nanofortnight
Teixobactin unfortunately isn't helpful to us. We really really need something
that works against gram negatives at the moment.

Also note that retrospective studies have shown that first observed resistance
to an antibiotic appears about six months after it is introduced. We are
producing new antibiotic families far slower than this rate.

------
christkv
When an organism develops resistance it usually makes an evolutionary trade-
off. This ironically might make them susceptible to older style antibiotics
who have been phased out. However retesting these antibiotics are not really
being done extensively due to there being little financial benefit.

[http://jac.oxfordjournals.org/content/70/8/2177.full](http://jac.oxfordjournals.org/content/70/8/2177.full)

My experience with kids is that here in Spain they are using older antibiotics
now to preserve the newer ones for serious infections trying to limit
evolutionary pressure on the bacteria.

------
eggie
Microorganisms have been able to cope with each other for damn near a billion
years using toxin-antitoxin systems. People are exploring these as negative
selection systems. Traditionally, antibiotics are used.
[http://nar.oxfordjournals.org/content/early/2015/03/23/nar.g...](http://nar.oxfordjournals.org/content/early/2015/03/23/nar.gkv248.short)

There is probably a huge array of such things out there. They are unlikely to
be as broad-spectrum as traditional antibiotics, but with research we should
be able to find ones to apply to the right situations.

At the same time as this crisis unfolds, our ability to know exactly what
someone is infected with improves. Soon sequencing of bacterial infections
will be the first step in patient triage. This will help us apply precisely
the right toxin to rid the body of the problematic type(s) of bacteria.

------
mkriss
Antibiotics resistance is getting stronger, probably because people eat a lot
of meat which is full of antibiotics. Because they feed animals with
antibiotics to grow faster and bigger. People should really think what food
they put in their body and less about some magic pill.

------
exabrial
Seems like this is time to research how antibiotic resistance is jumping
species. I feel like we could take advantage of unauthenticated exchange of
information and inject weaknesses instead.

~~~
Mz
Basically, when bacteria discover a gene that works, they share it with
others. As far as I know, this does not readily lend itself to a human
counterattack of some similar approach. The solution will likely come from
some other avenue.

~~~
eggie
They don't find it works then share. They are randomly sharing, and sometimes
it works. Bacterial sex.

~~~
Mz
You have to live to share. So, the distinction is essentially immaterial. They
find something that works, they live, they share randomly for kicks with other
bacteria they picked up at the bar, those bacteria become resistant, rinse and
repeat.

------
a3n
Are we using the older meds much, like penicillin? I wonder if bacteria
eventually lose their resistance to older meds with lack of exposure.

~~~
JunkDNA
In general antibiotic resistance is lost when it doesn't confer an advantage.
In some cases resistance to antibiotics costs cells energy they'd much rather
be spending on other things. When the antibiotic is gone, cells without the
energy tax can outcompete ones that do and divide quicker. The population then
reverts to sensitive cells again.

Even in a hypothetical case where a random enzyme mutation confers resistance
with no real obvious cost or side effect to the cell, unless there is specific
environmental pressure to keep that mutation, it can easily revert in
subsequent generations.

