
New antibiotic kills off persistent infections - oyvindeh
http://phenomena.nationalgeographic.com/2013/11/13/killing-sleeper-cells-and-superbugs-with-assassin-janitors/
======
mjn
Some background, based on quick research, not personal knowledge, so please
correct if anything's wrong:

This class of antibiotics, ADEP, was discovered as a naturally produced
substance isolated from the bacteria _Streptomyces hawaiiensis_ in 1985 (
_Streptomyces_ has been a fertile source of naturally occurring antibiotics).
After some promising results, there was work on synthetically synthesizing it
and producing "optimized" synthetic variants. ADEP4 is one of those, and was
reported in a paper published in 2005. There's a short 1-page summary of that
work in _Nature Reviews Drug Discovery_ 4: 957. See page 19 of this PDF,
article "Peptide power":
[http://journals2005.pasteur.ac.ir/NR/4%2812%29.pdf](http://journals2005.pasteur.ac.ir/NR/4%2812%29.pdf)

There's a lot of work trying to understand its mechanism, e.g. here's one
open-access paper that also has some background:
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955292/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955292/)

Here's the paper discussed in the linked article, unfortunately paywalled, but
with an abstract available that's actually a good summary:
[http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...](http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12790.html)

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Brakenshire
> isolated from the bacteria Streptomyces hawaiiensis in 1985 ... ADEP4 is one
> of those, and was reported in a paper published in 2005 ... [potential
> trials in coming years]

Gives an idea of the sort of development timescale we're talking about. It's
almost 30 years from isolation to this point. Clinical trials would take
another 10-15 years. So, if all goes well, that's 40 years from the initial
discovery until a doctor starts making up prescriptions.

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AaronFriel
The most understated portion of the article is that there is a method
discovered that can kill biofilms. The discovery of new antibiotics and
delivery techniques leaves me less optimistic for long-term change in the
availability of life-saving antibiotics. I suspect bacteria can, and will,
evolve around almost any mitigating technique we develop.

Yet I'm optimistic, because tools that crack biofilms are a new are of
development and promise hope for exploring new attacks on bacteria. Current
methods of biofilm dispersal are application of strong acids and bases or an
autoclave. You can't treat a hospital room with an autoclave, and
comprehensive treatment of a room with very strongly ionizing agents has its
own risks. There are other, experimental methods, but all are worth examining.

I hope research like this continues.

~~~
_Adam
>I suspect bacteria can, and will, evolve around almost any mitigating
technique we develop.

That's a baseless suspicion. Bacteria are ultimately bound by physical laws,
and while they've proven resilient, there's no reason to suggest we will be
unable to develop the means to annihilate them at will. Humans are creative -
bacteria just evolve fast.

I agree about the importance of the biofilm claim, but what they don't explain
is how they actually achieve this. Their method of disabling that particular
protein doesn't directly address the problem of the biofilms having a less-
permeable extracellular matrix.

~~~
AaronFriel
The problem of killing bacteria, as I see it, will increasingly become
something akin to the demarcation problem of philosophy. Why would it not be?
It is natural that the optimal situation for pathogenic bacteria to be in is
one in which they are indistinguishable from necessary cells. It may take an
extraordinarily long time, but until we are able to completely eradicate a
pathogenic bacteria _from the earth_ , we will remain in that arms race.

Humans are creative at killing bacteria, though it's already not difficult to
"annihilate them at will". It's much harder to annihilate only the ones we
don't like, only the ones that harm us, and only the ones that pose the
greatest risk.

~~~
HelloMcFly
I feel a more likely future scenario is one in which we create cell-sized
robotics that we can use for very narrowly targeted operations in the human
body, like treating bacteria. As the bacteria mutates, so does the targeting
mechanism in the software that programs the tiny robots.

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spindritf
> it only works the bacteria known as gram-positives, which includes
> problematic bugs like Staphylococcus

I have had one of those for almost a decade now.

> He hasn’t tested it in humans yet

How long is the road ahead before it becomes available to regular patients?
Should I get my hopes up?

~~~
giarc
It's going to be a long time before it is readily available for human use.
Expect three, maybe four stages of clinical trials. There is also the risk
that it doesn't even work in humans or has major side effects that outweigh
the benefit.

This is sensationalism news, or as it is most often called, news.

~~~
javanix
I would call it a sensationalist title, but the article itself is far from
sensational.

I actually found the writing to be pleasantly balanced and scientifically
detailed, without jumping to unreasonable conclusions.

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analog31
If this is a novel antibiotic with any therapeutic potential, please let's
outlaw feeding it to cattle by the ton.

~~~
GoodIntentions
Pretty much exactly what I was going to post. Prophylactic use of antibiotics
in hogs/whatever is stupidity in a class of its' own, selectively breeding
organisms on an industrial scale for resistance to the drugs we might want to
use to keep us alive.

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shawn-furyan
This is an awful headline change. National Geographic's title (Killing Sleeper
Cells and Superbugs with Assassin Janitors) wasn't very descriptive, but at
least it didn't leave room for a headline browser to take away the false
conclusion that the CDC declared public health crisis of antibiotic resistance
is near resolution.

According to the article, this new antibiotic has only been tested on mice and
rats. These sort of preliminary results go bust all the time, and so I think
that in this case, it's irresponsible to fail to indicate that these are
preliminary studies and that the effect hasn't been demonstrated in humans.
This could have been achieved by leaving the title the same, or by changing it
to "New antibiotic kills off persistent infections in rats".

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jes5199
Reading about new treatments gives me a kind of anxiety: drug trials are so
slow and the funding models are so removed from the actual human life-saving
potential, that I just am filled with fear that this stuff will get mired in
bureaucracy or otherwise defunded rather than getting FDA approved. I dread
the idea that someone I know to get sick and die because we're so ploddingly
slow at doing these trials.

For example: "DRACO" antivirals from MIT, were developed in 2011, and
according to mouse model tests and tests on cultured human cells, is safe and
effective against influenza and rhinovirus and everything else they threw at
it (see [http://mackinstitute.wharton.upenn.edu/wp-
content/uploads/20...](http://mackinstitute.wharton.upenn.edu/wp-
content/uploads/2013/02/Rider-Todd_PANACEA-Broad-Spectrum-Antiviral-
Therapeutics.pdf) for details), and yet it could be a decade before we even
try to answer questions like "wait, does this cure HIV? It sounds like it
might actually cure HIV"

~~~
Fomite
The funding models actually aren't removed from the actual human life-saving
potential. The NIH has been pushing translational research pretty heavily, and
if anything there's been a fair amount of pressure on the basic science types
to tie their research to something, anything that will manifest in Saving
Lives.

Beyond that, it absolutely _should_ take drugs many years to come to market.
Research is hard. Research on human beings is _very_ hard. You can't just take
shots in the dark and hope something sticks - you have to understand how, and
how well, something works. Even for the established antivirals we do have for
HIV, we're still trying to figure out who to give them to and when.

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Houshalter
The bacteria evolving to go dormant reminds me scale insects that damaged
citrus fruits. The farmers put a giant tent over every tree and gassed them.
This worked at first, but after a few years the scale insects got resistant.
Whenever startled, they would sit perfectly still and hold their breath for
half an hour.

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sgarlatm
It's nice to know that despite all the alarmist articles about the end of
antibiotics, good progress is being made. If this works, it could completely
replace traditional antibiotics. In that case, I could see dozens of new drugs
in this class developed by the antibiotic companies. This would be similar to
the race to develop new antidepressants, HIV drugs, and erectile dysfunction
drugs. Any drug you have to take over and over again is a huge draw for the
pharmaceuticals.

~~~
giarc
This won't completely replace traditional antibiotics. As the article states
this acts on Gram positive persister cells (a very specific group). The coming
storm is from Gram negative bacteria such as Klebsiella, Actinetobacter and
Pseudomonas.

There is actually very little activity occurring in the field of antibiotic
drug discovery and you identified the issue; no money in drugs that someone
takes for 14 days and stops. Pharmaceutical companies are driven by
stockholders and therefore they want them developing drugs that someone takes
for the rest of their life (anti-depressants). Much of the research for abx
discovery comes from academia who struggle with budgets that are pennies
compared to what Pfizer, GSK, Wyeth, Astra can afford.

~~~
JunkDNA
You're right that it's about profits when pharma is involved, but you are
wrong about the reason (otherwise vaccines would not exist). I can tell you
from firsthand experience that the length of time someone is on a drug makes
almost no difference in where research priorities are.

The primary issue with antibiotics is that since the late 1990's, if you
succeed, and you develop the _best_ antibiotic the world has ever seen, the
FDA will require it to be a "drug of last resort". It will therefore sit on
the shelf and be guaranteed to not be prescribed very much during the life of
its patent. Once enough time goes by, and other drugs come out _if_ (and
that's a big _if_ ) it is no longer a drug of last resort, it is likely off
patent and therefore can be made in generic form for pennies by generic
manufacturers. Regardless of what you think about patents, these incentives
are completely misaligned with companies going all-in and taking a risk on new
antibiotics.

~~~
giarc
Vaccines are a bit of a different class as some are exempt from adverse
reaction lawsuits and therefore risk is reduced for the companies
manufacturing the vaccine.

I think your assessment that my argument is "wrong" is inappropriate. You'll
see that my argument is supported by the WHO (Bulletin of the World Health
Organization 2011;89:88–89).

>Another reason is commercial. Antibiotics, in particular, have a poor return
on investment because they are taken for a short period of time and cure their
target disease. In contrast, drugs that treat chronic illness, such as high
blood pressure, are taken daily for the rest of a patient’s life. “Companies
have figured out that they make a lot more money selling the latter drugs than
they do selling antibiotics,” Spellberg says, highlighting the lack of
incentive for companies to develop antibiotics.

~~~
Fomite
And yet in a recent survey of drug development costs, "Difficid", by Optimer
Pharmaceuticals, was one of the most inexpensive to develop.

I also really don't buy the "return on investment" argument, as curing a
bacterial disease rarely provides immunity.

It's also not my experience as a researcher in the area - several drug
companies are actively funding research.

~~~
giarc
Fidaxo also may not be that great or cost effective[1]. Optimer, I believe has
been bought by Cubist and delisted from Nasdaq. 1. Clin Infect Dis. 2013
Aug;57(4):555-61

~~~
Fomite
I do know their most promising findings don't get reflected in clinical trials
well. But "The Drug Companies aren't there" isn't addressed by a small drug
company specializing in ID getting bought about by another drug company that
has tons of ID products for half a billion dollars.

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atmosx
That's very good news actually. If first stage trials are successful might be
marketed sooner than expected. However, I didn't read the paper, so I can't
comment on the mechanism of action which the mos interesting part of an drug.
Bacteria might become resistant if this procedure becomes overused (as usual)
and it would be a shame.

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driverdan
Very interesting research but it doesn't mention any negatives of ADEP4. What
kind of effects could it have on the human body?

~~~
Fomite
Many antibiotics are fairly nasty drugs - they're associated with kidney
failure and other negative outcomes, especially for long term treatment. But
it's hard to know for sure until things progress to the point where we are
doing toxicity studies.

Which you don't bother with until you know the thing can work in the first
place.

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davidjnelson
I wonder if this approach will eventually be useful in eliminating Chronic
Lyme Disease.

~~~
Fomite
Doubtful, as there's little to no scientific evidence that Chronic Lyme
Disease is actually a bacterial infection.

~~~
brandoncarl
That's actually a bit of a dated response:

See recent study on Rhesus monkeys:
[http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...](http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029914)

The "no bacteria" perspective is usually based off of IDSA guidelines.
Unfortunately, they've been successfully litigated against for providing
incorrect information that appear to be linked to financial interests:

"My office uncovered undisclosed financial interests held by several of the
most powerful IDSA panelists. The IDSA's guideline panel improperly ignored or
minimized consideration of alternative medical opinion and evidence regarding
chronic Lyme disease, potentially raising serious questions about whether the
recommendations reflected all relevant science."

[http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284](http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284)

Good summary of Lyme:
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636972/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636972/)

Needless to say, we've got a lot of people we're telling that they are not
sick when symptomatically they appear to be.

~~~
evacuationdrill
"Pursuant to their agreement with Blumenthal the IDSA guidelines were reviewed
by an independent panel subject to strict conflict-of-interest guidelines and
vetted by a medical ethicist. The panel supported the original IDSA
guidelines, finding that "chronic Lyme disease" and "post Lyme syndrome" lack
clear definitions and convincing biological evidence. Further, the report
emphasized that several prospective clinical trials of prolonged antibiotic
therapy for persistently symptomatic patients uniformly showed evidence of
harm without convincing evidence of benefit.[22] Nonetheless, some groups have
continued to criticize the IDSA guidelines after the 2012 review.[23] [24]"

[https://en.wikipedia.org/wiki/Infectious_Diseases_Society_of...](https://en.wikipedia.org/wiki/Infectious_Diseases_Society_of_America#Lyme_disease_treatment_guidelines)

Also, see your sibling post by me with info from the CDC. It doesn't seem like
they're dismissing the symptoms, they're just saying that antibiotics don't
help.

~~~
brandoncarl
I've watched my mother suffer from this for 20+ years. She initially had a
doctor that treated her for 3 years with very strong antibiotics. She made
remarkable progress. The doctor left practicing for personal reasons and
subsequently she couldn't find good medical help. Her condition deteriorated
over the years.

While the CDC doesn't seem to dismiss symptoms, I've watched dozens of doctors
dismiss her. I've received calls from dozens of people who all have the same
set of symptoms. I've also seen people get better only after years of
antibiotic treatment, and slowly at that. My friends in medical school have
indicated that they receive about two hours of Lyme-related training during
their education.

The issue that you have is three-fold:

1\. Ticks often carry multiple infections (Borrelia Burgdoferi, Bartonella,
Mycoplasma, and Babesiosis). Each of these infections can leave the immune
system in a dysfunctional state. Most studies only focus on treatment of BB,
leaving the other infections untouched.

2\. Given that, for the toughest cases, years of antibiotics may be needed, it
is extremely difficult to keep studies "controlled". i.e. a week long study
may not have much variability, but over a two-year study, a lot happens. The
noise increases relative to the signal.

3\. BB has very high genetic variability. This leads to the potential for
larger numbers of strains, with over 200 thought to be in existence.

I'm not contesting that this isn't well-understood. In fact, I fully agree
with that. But statements like there is little to no evidence that Chronic
Lyme exists are inappropriate. This is an area that has historically been
underfunded, and it has a pretty rich history of controversy. We can fight
over nomenclature all day long, but that doesn't change the fact that a lot of
people are suffering, and the broader medical community is woefully
uninformed.

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ffrryuu
But does it kill the host as well?

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scottrudy
can it be tested on Google+?

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throwaway0094
> New antibiotic kills off persistent infections

Now available in hand-soap.

~~~
angersock
oh god _damn it_ >:(

