
Antibiotic resistance: The last resort - dn2k
http://www.nature.com/news/antibiotic-resistance-the-last-resort-1.13426
======
timr
Things like this make me increasingly sad for our priorities as a society.

I realize that not everyone can be a biochemist and do antibiotics research,
but we've reached a place where our most technologically savvy people are
frittering their talents on food delivery services and cat videos. I have an
advanced degree in biochemistry, and it's still basically impossible to get
work doing antibiotics development. There's no money in it. I work on
websites, because that's where I need to be to earn a living. If I could get
venture capital to do speculative work developing new classes of antibiotics,
I'd do that in a heartbeat.

What's the point? I don't really know. Rome is burning, I guess. Bring on the
bread and the circuses.

(Postscript: $200M is considered a big initiative in this space. We spend
BILLIONS on niche diseases:
[http://online.wsj.com/article/SB1000142412788732397500457849...](http://online.wsj.com/article/SB10001424127887323975004578499324161473326.html))

~~~
harshreality
When very bad outbreaks start to occur because antibiotics' effectiveness
starts dropping precipitously, I think there will be progress. It will take a
few years to get ramped up, but given modern technology I think there will be
some interesting partial solutions fairly soon after that.

The Russians were particularly interested in this sort of thing during the
latter part of the Cold War, as I'm sure the West was, and still is. They were
looking at enhancing the immune system as an alternative to antibiotics or
vaccines for agents that could not necessarily be fought with antibiotics or
vaccines (i.e. biological terrorism). They also looked at using immune
response as a bioterror target (e.g. something like the reaction to TGN1412
but using a transmissible bioagent instead of a non-biological agent.) They
were keenly aware that the two problems were linked.

Obviously, immune response is bad at all times when there's no active
threatening infection to fight, but needs to be maximized at least along
certain paths when there's a threatening infection. That was a difficult
problem with 1980's technology. I'm optimistic that it's not quite so
intractable a problem, at least in cases of common bacterial infections
typically treated with antibiotics today. More narrowly targeted immune system
boosting seems plausible now that there's a somewhat better understanding of
immune system interactions...

~~~
hga
" _enhancing the immune system_ "

Note that one possible flip side of this is auto-immune diseases.

" _immune response is bad at all times when there 's no active threatening
infection to fight_"

I don't think that's at all true. Our immune systems tend to work wonderfully
most of the time given that we're constantly bathed in potentially pathogenic
bacteria. In this discussion scythe says of " _the ESKAPE pathogens, which are
the primary superbugs_ " that " _in every case except S aureus, infection is
basically unheard of when an individual has a functioning immune system; they
are all opportunistic pathogens_ ". I take that to mean that for a lot people,
_temporary_ immune system dysfunction, e.g. due to other insults to the body,
are a big factor.

I noticed on Wikipedia that one of the ESKAPE bacteria, _Acinetobacter
baumannii_
([http://en.wikipedia.org/wiki/Acinetobacter_baumannii](http://en.wikipedia.org/wiki/Acinetobacter_baumannii)),
" _Colloquially,_ A. baumannii _is referred to as 'Iraqibacter' due to its
seemingly sudden emergence in military treatment facilities during the Iraq
War. It has continued to be an issue for veterans and soldiers who serve in
Iraq and Afghanistan. Multidrug resistant (MDR)_ A. baumannii _has spread to
civilian hospitals in part due to the transport of infected soldiers through
multiple medical facilities._ "

That I assume is largely due to gross trauma (and lots more soldiers surviving
because of _much_ better body armor (even helps in non-comat accidents I've
read) and ever better treatment) ... and e.g. car crashes in the US tell us
we're not soon going to be rid of that problem....

~~~
harshreality
I realize that auto-immune disease is a consequence of overactive immune
system, and I thought I alluded to that in the last paragraph. I guess I don't
believe that the _only_ way to _enhance the immune system_ is to make it more
active in general or in ways that would necessarily lead to increased
instances of autoimmune disease.

I should have said _wherever_ rather than _at all times when_. I don't try to
discuss this a lot so I guess I'm not as precise at organizing my thoughts as
I'd like to be. Thanks. Yeah, "superbugs" are disproportionately at hospitals,
and garden variety bacterial species; they cause problems because patients
tend to have wounds or compromised immune systems, and because the frequency
of antibiotic use at hospitals encourages thriving populations of resistant
strains.

~~~
hga
Ah, yes, I can see that now, " _[m]ore narrowly targeted immune system
boosting_ " is definitely an option. Although ... do we want everyone in the
country/world taking the same "ImmuneBoost(TM)"...? (Not a particularly useful
criticism, but still something to also think about.)

Especially if we can find ways sufficiently weighted towards bacteria. The
major thing that saves us with them is that their significant low level
differences from eukaryotic cells, e.g. those smaller and different ribosomes
that provide a handy target for various antibiotic families (they're the
organelles that synthesize proteins). Or their plant style cell walls.

(I stopped paying attention to the details of immune system in the late '70s
when I noted how fast we were learning about it, i.e. for me it's something to
learn/review "on demand", so I can't make any really specific suggestions as
to what to do or judge the feasibility.)

~~~
harshreality
I'm a fan of distributed separately-evolving defenses, and identical
ImmuneBoost(TM) given to everyone, that has the same effects in everyone,
could I suppose create susceptibility to some HIV-style pathogen that triggers
and/or hijacks the specific boosted aspects of the immune system. HIV is very
careful (i.e. has evolved) to stay dormant for a long time... it probably
didn't start out that way, and suffered as a result. Any sort of pathogen that
targets the immune system has to be similarly careful; otherwise it suffers
the same fate of all extremely lethal pathogens: killing the host population
faster than it can spread.

Another promising research avenue is bacteriophages. I don't know why it's
being pursued more in the former Soviet Union than it is in the West. I
suppose even with targeted bacteriophages there's some risk that they could
mutate and start targeting beneficial bacteria, which would be a problem.

A cute CS-inspired theoretical approach would be to throw variable layers at
the problem. With genetic engineering, create bacteria that function as a
supplemental immune system, but in a very narrow way; the bacteria would,
possibly in collaboration with the host immune system, generate specific
bacteriophages for any pathogenic bacteria they come into contact with.
Obviously it wouldn't work against pathogenic _viruses_ , but other than the
(perhaps impossible) difficulty of having a cell able to generate novel
bacteriophages, it doesn't seem so outlandish. If we get to the point where we
can write code for a wide variety of biological activity and get it translated
into DNA, then such a bacteriophage-generating bacterium might be possible.

I realize there are pathologies imaginable with any possible solution. The
question is how likely is it that natural or engineered pathogens will target
whatever new targets are available. Bacteriophage-generating bacteria could be
hijacked by viruses, mutated by gene transfer with harmful bacteria to do bad
things, or even give their bacteriophage-generating properties to pathological
bacteria which might then gain mutations to generate human-targeting
viruses... wouldn't _that_ be fun.

------
fragsworth
> Davies, the United Kingdom's chief medical officer, described CREs as a risk
> as serious as terrorism

This is a descriptive strategy people need to use more often to put things
into perspective for the average person and taxpayer. Many diseases pose risks
vastly more serious than terrorism, but receive far less attention.

However, if you're aware of the actual risk of terrorism, something that is
"as serious" as terrorism is really not very threatening.

~~~
cabalamat
Yes. When I read that I thought "so, over-hyped and not really a problem,
then".

~~~
jurassic
The predicted 1/6 death rate for routine surgeries made a big impression on
me. A literal roll of the dice. Think of everyone you know who's had a
surgery, and it's obviously a radically bigger problem than terrorism. I'd
like to see a comparison to death rates from common cancers or heart disease
that some people actually worry about.

~~~
hga
That might be, shall we say, a somewhat short term problem as the population
is culled of less hardy individuals. When I think of the Mayo brothers using
the Murphy Button zillions of times to splice together someone's small
intestines, I realize that a lot of dangerous surgery was done with enough
success in the pre-antibiotic era. One in which my parents, born in the
mid-30s, grew up in; their attitudes towards sickness and death are markedly
different than people younger who e.g. wouldn't have survived without
antibiotics.

~~~
LaGrange
Please, do realize that if resistances were free, we would all be resistant
already. We lived with those infections far longer than we did without.
TANSTAAFL applies here as well, and even if the evolutionary pressure gets
high enough to cause change (which will be far, far later than you'd like it
to be, i.e. serious social trouble probably has a significantly lower
threshold), it will be at a cost that is hard to predict, though likely it
would be lowered resistances to something else, or maybe a higher risk of
autoimmune diseases. Or something completely different.

~~~
lostlogin
For those like me: There Ain't No Such Thing As A Free Lunch.

------
DanBC
Something else that's scary is drug-resistant gonorrhea, which has been found
in Japan. ([http://www.reuters.com/article/2011/07/11/us-gonorrhoea-
supe...](http://www.reuters.com/article/2011/07/11/us-gonorrhoea-superbug-
idUSTRE76A0YO20110711))

I've posted this clip before, but in case you missed it:

([http://v6.tinypic.com/player.swf?file=24goih4&s=6](http://v6.tinypic.com/player.swf?file=24goih4&s=6))

Here's a short snippet from a BBC Television programme (Horizon - 'defeating
the superbugs')
([http://www.bbc.co.uk/programmes/b01ms5c6](http://www.bbc.co.uk/programmes/b01ms5c6)).

It shows E.Coli developing anti-biotic resistance. There's a tray of nutrient
jelly. The jelly is divided into sections. It starts with no antibiotic. Then
there's a normal dose. Then there's a 10x dose, followed by 100x dose,
followed by 1000x dose. The limits of solubility are reached - they cannot
dissolve any more antibiotic into the jelly.

Then they drop E.Coli onto the normal jelly, and use a time lapse camera to
show the growth.

After just two weeks the bacteria is able to live on the 1000x dosed jelly.

It's pretty impressive demonstration.

(Apologies for the suboptimal hosting site. YouTube's contentID blocks this
video worldwide.)

~~~
throwaway1979
Thx so much for the video.

I am very confused though ... the documentary implies that the bacteria are
developing the immunity through evolution ... over millions of cell divisions.
But how can this be happening so fast? If a bacteria were to be countering the
antibiotic via an enzyme, it would take an insane amount of time to develop
that enzyme by pure chance. It is more likely that some of the bacteria
already had the anti-antibiotic enzyme and we're seeing selection in progress.
Can someone please please explain?

~~~
hga
When I was doing some molecular genetics on _E. Coli_ in the summer of 1977 I
was told that for many antibiotics, 1 in a million of them would spontaneously
mutate and develop resistance if exposed, and 1 in a billion for streptomycin.

Note that there are _many_ methods of antibiotic resistance, including little
pumps that try to keep the level low enough inside the bacterium. They've been
developing them for a very long time, the other insight you need into this is
the ecological one.

Most are from molds, and they release them to better compete with bacteria.
And a resistant bacterial strain will not necessarily compete well with others
lacking its mechanism(s) because those are otherwise maladaptive . E.g. it's
spending raw materials and energy producing a β-lactamase while its
competitors are dividing more rapidly. Only when you add the selection
pressure of the antibiotic does it win big.

~~~
mjn
There's also a strong role for horizontal gene transfer in antibiotic
resistance, e.g. by swapping plasmids, which can allow bacteria to swap
higher-granularity mechanisms, rather than having to evolve them from scratch
with random mutations.

~~~
Peaker
This feature is basically bacterial sex and turns their evolution from a slow
serial computation to a highly parallel computation that gives an
__exponential __speedup in evolution.

I think this effect is the extremely under appreciated benefit of
sex/exchanging dna.

------
scythe
>That means, say infectious-disease experts, that their best tools for
defending patients remain those that depend on the performance of health
personnel: handwashing, the use of gloves and gowns, and aggressive
environmental cleaning. Yet even research that could improve best practices
has been short-changed, says Eli Perencevich, an infectious-diseases physician
and epidemiologist at the University of Iowa in Iowa City who studies how
resistant bacteria move around hospitals. _“We haven 't invested in research
in how to optimize even standard infection-control practices. We just blame
the health-care workers when they go wrong.”_

It seems that a possible positive outcome of this could be cleaner hospitals.
No infection is better than a treatable infection. Even if CREs are
controlled, even if new antibiotics are developed, these outbreaks will keep
happening and resistance will keep developing. Developing effective yet
practical hygiene procedures is the only way to solve the problem once and for
all.

~~~
LaGrange
It's harder than just "cleaner". The bacteria killed in disinfection
procedures tends to leave space for more horrifying stuff that's also more
resistant – you won't really find
[http://en.wikipedia.org/wiki/Staphylococcus_aureus](http://en.wikipedia.org/wiki/Staphylococcus_aureus)
on toilet seats outside of hospitals, unless you went and used Vircon on them.

~~~
eurleif
Would introducing probiotics after disinfection do anything?

~~~
LaGrange
It's complicated, and quickly gets outside of my knowledge (I was only mildly
involved in hospital stuff), but one big problem is, the same bacteria can be
beneficial or lots of trouble depending on where it is, and you may be
reintroducing exactly the same thing you just killed (think E.Coli).

------
w1ntermute
> Initially, most individuals carrying bacteria with the new resistance factor
> had some link to clinics in India

One big problem is that in India, lack (or poor enforcement) of regulations
results in abuse of antibiotics, which leads to the development of resistance.
People are also much more susceptible to infectious disease, due to poor
public health policy (lack of clean water, etc.).

~~~
cageface
This is a big problem in SE Asia too. Here in Vietnam I don't think I've ever
seen _anyone_ come back from a visit to the doctor without antibiotics, and
pharmacies dole them out like candy without prescriptions. What's worse is
that they seem to always provide only a day or two worth of pills, which in
most cases isn't enough to do anything.

~~~
marvin
How on Earth can this happen? Doesn't Vietnam have trained doctors? This
practice is ridiculously dangerous? Why?

~~~
manmal
I've been to a Greek island a few years ago (Korfu). A friend of mine walked
into a drugstore, told them he has a cold, and walked out with some broad-band
antibiotic. No questions asked.

------
chestnut-tree
Many years ago, I remember seeing a BBC documentary about phages that were
(and are) used in Russia and former Soviet states in place of antibiotics.

What are phages? _" Phages are naturally occurring viruses that kill bacteria.
Once they get into bacterial cells the phages' DNA replicates until it kills
the host.

Doctors in Georgia, and in other countries that were in the former USSR, have
been using this therapy for 90 years. But medics and drug regulatory bodies in
most places in the developed world have been reluctant to accept that it
works."_

From:
[http://www.bbc.co.uk/news/health-21799534](http://www.bbc.co.uk/news/health-21799534)

~~~
jotm
Too bad they were largely abandoned because antibiotics were cheaper and
easier to produce (a situation similar to electric vehicles in the early
1900's, in fact)...

~~~
tsotha
It wasn't just that. The problem with phages is it's impossible to make enough
for a therapeutic dose without introducing mutations, so you're never
completely sure what you're giving the patient. They're just not as safe as
conventional antibiotics.

We'll probably end up using phages because we won't have any other choice. But
that's not a step forward for patients.

~~~
bhickey
I'm not sure this analysis is accurate. At any rate, I don't share your
concerns.

The big problems with phage are:

    
    
       1) Narrow spectrum
       2) Readily cleared by the immune system
       3) Bad at killing bacteria in comparison to antibiotics.
    

I worked with a a strain of Phi X174 that was optimized for a particular host
by serial passages. It did a number on petri dishes, but I'm skeptical that it
could have done much to clear wild type e. coli. Antibiotics are good and bad
because they indiscriminately kill everything. If phage are every used in a
widespread manner, I imagine they'd get deployed in a cocktail to broaden the
spectrum.

It's easy to make highly pure phage. Colonies are clonal and form plaques when
plated. If you did serial passages to ensure that the phage was near some
local fitness maxima, it's unlikely that selective effects would move it away
from that maxima. In Phi X174, which admittedly has a short genome (5386bp), I
would have been surprised to see any clones with mutations. I was doing site-
directed mutagenesis to change single base pairs, so I thought about this a
lot. Worrying over a couple of base flips when mass producing phage is simply
a hallucinatory fear.

At least one phage is dangerous, but I'm not aware of any other examples. CTX
is a temperate phage that makes cholera produce toxin. There is a risk of
immune response. The immune system tends to get pissy when you inject foreign
matter. I've seen studies that compared oral dosing to intramuscular phage and
IM seems to be the way to go for higher blood titers. In one study, serial
passages were performed in rabbits. The phage acquired mutations in its capsid
proteins and over several generations blood titers increased by something like
two orders of magnitude. (I don't recall if they used the same rabbits or
naive rabbits.) Makes you wonder if we could recover super fit phage from
people receiving phage treatment?

Finally, with regards to safety, phage are currently in use as an anti-
microbial again listeria.

~~~
tsotha
Is "highly pure" really pure enough for the FDA? I knew a guy who worked on
phages. The problem they ran into is when they submitted their virus to the
FDA there was no way they could guarantee the absence of dangerous mutations
in a given batch.

EDIT: I should say I didn't follow his work that closely, so it's possible
there were efficacy problems as well.

~~~
bhickey
The bar has certainly been met with regards to phage as a food additive:
[http://www.fda.gov/OHRMS/DOCKETS/98fr/cf0559.pdf](http://www.fda.gov/OHRMS/DOCKETS/98fr/cf0559.pdf)

The error rate of an E.coli DNA polymerase in vitro in <9x10^-6. Lambda phage,
for example, has a genome that's about 48 kilobases in length. Which gives a
mean error rate of 0.432 bases / replication. Ballpark estimate that the phage
goes through 30 replications to produce a plaque, so we're talking ~13
mutations (it's a little different than that due to the founder effect, etc).

It isn't like a phage is going to jump Kingdoms and start predating you
instead of the preferred host. This simply isn't a realistic risk, while the
immunogenicity issues could be.

In terms of my own risk tolerance, I would have been comfortable drinking any
of my own samples.

~~~
tsotha
>In terms of my own risk tolerance, I would have been comfortable drinking any
of my own samples.

Hmmmm. Maybe so, but would you inject them?

~~~
bhickey
If there was a medical need and they were shown to be efficacious, sure.

I'm currently receiving allergy shots which involves frequent injections of
dust mites. Injections are followed by a 30 minute observation period as a
caution against anaphylaxis. Staff are on hand to intubate. The frequency of
life threatening reactions is around 1 in 10^6.

If phage were ever used clinically, I suspect the protocol would be similar. I
mean, heck, some people have life threatening reactions to common antibiotics
(I believe sulfa allergies are particularly common), but that doesn't keep
them out of use.

------
jivatmanx
The lack of advancement in antibiotics is a stark contrast to the recent
improvements in treatments for so many chronic diseases.

Whatever the reason the free-market pressures here are so weak, antibiotic
development should consequently be a priority in government grants. I wonder
if there could even be intergovernmental cooperation here?

~~~
etiam
Huge costs and virtually no gain. A good antibiotic is used during a short
term. Furthermore if things go on like today it will probably be destroyed
within years by short-sighted, irresponsible use like fattening cattle. Any
pharmaceutical company suicidal enough to start development with those odds
will probably have put itself out of business long ago already.

This is an existential threat in many ways. Infections we shrug at today are
going back to being life-threatening. And it isn't just infectious medicine
that's losing power by this. Surgery, for example, get vastly more dangerous,
difficult and expensive if there isn't effective antibiotics; in some cases
downright impossible.

I think you are right about public funding to the research and expect to see
it rise. Where I would really like intergovernmental cooperation is in making
sure the new antibiotics are used in a responsible, sustainable way. Routine
use like an agricultural food additive should be a felony as far as I'm
concerned, and even when used for curing serious disease it should be high
priority making sure cures are completed and risk of transmitting resistant
bacteria is minimal. We have to protect antibiotics effectively if there is to
be much point in developing new ones.

~~~
hga
" _Furthermore if things go on like today it will probably be destroyed within
years by short-sighted, irresponsible use like fattening cattle._ "

Which of course explains the widespread use of vancomycin for that purpose.

Seriously, while this use of antibiotics is problematic, there's no _evidence_
it's a big problem _today_ \---if there was it would be written in flaming
letters across the sky.

" _Where I would really like intergovernmental cooperation is in making sure
the new antibiotics are used in a responsible, sustainable way._ "

How does this work? What happens to a bad actor who doesn't care or just can't
get its act together?

~~~
cabalamat
> How does this work? What happens to a bad actor who doesn't care or just
> can't get its act together?

Governments could refuse entry to people who've visited that country.

~~~
hga
And do what at the borders, many if not most of which are porous?

~~~
rwallace
The vast majority of people moving between countries pass openly through
airports or border checkpoints where they could be turned back. Yes, there are
illegal immigrants and drug traffickers who sneak across the desert or dodge
the Coast Guard in motorboats, but they represent an insignificant fraction of
total human traffic and opportunities for carrying antibiotic-resistant
disease.

------
jechmu
Another reason (which I wish I had known) to treat antibiotics as a last
resort is Clostridium difficile (C. diff). In addition to killing the bad
bacteria in your body, antibiotics will also kill the good bacteria in your
gut. This in combination with exposure to C. Diff (rampant in US hospitals) is
a very bad thing.

When the good bacteria in your gut is killed, it frees up real estate giving
any present C. diff an opportunity to overgrow and wreak havoc. If this
happens, the road to recovery can be very long. And to add insult injury it
takes bleach to kill any C. Diff you happen to spread to surfaces in your home
and this often results in patients re-infecting themselves repeatedly.

~~~
DennisP
I talked to the sellers at an estate sale, and found out the deceased, a lady
in her 60s, had been killed by C. diff. Took about four days.

------
zw123456
My Mom was I guess sort of a hippie ahead of her time but she used to always
rail against anti-bacterial soaps and etc. She used to resist using the
dishwasher and anything anti-bacterial, and would say that it was good for
your immune system to be exposed to germs once in awhile. The joke in the
family was that she just did not want to have to do too much housework, But
actually, she may have been on to something.

~~~
DennisP
A microbiologist at our local university was interviewed on our public radio
station a couple years ago. He pointed out that antibacterial soaps may kill
99.5% of the bugs but the ones left are the resistant ones, with an adaptation
that also makes them resistant to some human antibiotics. Then with the other
bugs killed off they'll have a nice open field to spread.

A schoolteacher called in and said "I have to use antibacterial soaps, you
have no idea what I have to deal with in my classroom." The guy replied, "You
can't get rid of the bacteria. Your choices are a surface covered with normal
bacteria, or a surface covered with antibiotic-resistant bacteria."

------
plg
As laypeople we seem to think about this issue much like programmers think
about algorithmic efficiency ... who cares if my code is messy, slow and non-
optimal, all I need to do is wait a few years for CPU speed to double and
nobody will notice.

i.e. most people think, just wait a few years until the scientists develop a
better antibiotic. Cat and mouse.

------
joshuak
Just out of curiosity does anyone know of research proving or disproving the
viability of using 'safe' bacteria to defend against dangerous bacteria?

I've often wondered since we've selected for super bugs buy killing off the
easy to kill ones with antibiotics, couldn't we intentionally reintroduce the
easy to kill ones (or something similar but benign) so that the super bugs
have no population advantage? Instead of being the only guys on the playing
filed they'd have to compete with the benign bacteria which would, in my
thinking, limit their growth potential.

~~~
refurb
Not quite the same thing, but do a google search for "fecal transplant"

Patients who have undergone antibiotic therapy will sometimes get infected
with C. difficle bacteria. It's very hard to treat and can sometimes cause
toxic megacolon.

If you take the feces of a healthy individual and transfer it to a C. difficle
patient, the good bacteria will crowd out the bad bacteria and cure the
patient.

The FDA just released some guidance on the procedure.

~~~
joshuak
Yeah, I know about that, and I'm not talking about intestinal fauna, but
rather infectious disease. Nevertheless, it is similar logic to what I'm
suggesting.

------
tmoertel
What seems surprisingly ignored by most of the medical community is that many
microorganisms harmful to humans can thrive only in environments that have
been artificially stripped of the normally dominant microorganisms that humans
are mostly well adapted to. Instead of fighting an ever-escalating arms race
against resistant microorganisms in some imaginary “war on germs,” maybe we
ought to stop screwing with the normal microbial environment and start
learning from it instead.

I mean, is it really so surprising that when you salt sliced cabbage and let
it sit in a crock for a few weeks – no preservatives, no antibiotics – that
what you end up with, after the ambient microorganisms have had their way, is
not only perfectly preserved cabbage but also _delicious_? That fermented
foods naturally arise when you let traditional foods “go bad” and that they
taste so good ought to suggest something. It’s almost as if millions of years
of natural selection in an environment devoid of modern preservatives and
antimicrobial agents has made humans well adapted to (and even crave) the
microbiota that naturally dominate the places where humans have traditionally
lived and the foods that humans have traditionally eaten.

Taking us out of those environments makes our bodies and foods and hospitals
competiton-free zones for modern “superbugs.” Seems like a really bad idea.

~~~
scythe
It's all well and good until you're immunocompromised. _S. aureus_ itself is
commensal. Ditto _E. faecium_ , _K. pneumoniae_ and _Enterobacter_. Meanwhile
_A baumanii_ and _P aeruginosa_ are widespread in soil. Together these
represent all of the ESKAPE pathogens, which are the primary superbugs:
_Enterococcus faecium_ , _Staphylococcus aureus_ , _Acinetobacter baumanii_ ,
_Pseudomonas aeruginosa_ , and _Enterobacter_ [all _Enterobacter_ ]. That is
to say: the six bacterial strains [excluding _Mycobacterium tuberculosis_ ,
guess what it causes] carrying the most severe antibiotic resistance and
responsible for the worst infections are the very same strains present all
around us naturally. However, in every case except _S aureus_ , infection is
basically unheard of when an individual has a functioning immune system; they
are all opportunistic pathogens. This is a part of the problem: a healthy
individual can carry a dangerous strain around with no idea of the risk they
present to the immunodeficient.

So what is to be done with the immunocompromised? There are some heroic
medicine case studies of an "immune system transplant", notably the remission
of HIV, and perhaps this method could be made more viable.

~~~
tmoertel
Don't you suspect that a large portion of "a functioning immune system" _is_
the naturally occurring human microbiome (e.g., especially in the gut)? So
isn't any rational response to the question _What is to be done with the
immunocompromised?_ , in part, to stop compromising people's immune systems by
screwing up their microbiomes?

Yes, people become immunocompromised in other ways, but I'd wager that a large
portion of compromised immune function in modern society is caused by our
screwing around with antibiotics and other antimicrobial agents on a large
scale without understanding what the hell we're doing. The "germs are bad"
model of medicine is overly simplistic and gets important things wrong and, as
a result, is long-term harmful.

Until mainstream practice catches up with the reality that our environment,
including our microbiota, are part of the properly functioning human organism,
we're going to cause a lot new problems for ourselves by trying to fix the
"old" problems.

~~~
hga
Errm, you are aware that people got these infections, and died in droves from
them, long, long before the age of antibiotics, or "germs exist", let alone
are "bad"?

This is a grander version of the hygiene hypothesis
([https://en.wikipedia.org/wiki/Hygiene_hypothesis](https://en.wikipedia.org/wiki/Hygiene_hypothesis)),
but unlike it I don't see a phenomena to explain.

~~~
tmoertel
Who is claiming that microorganism-involved disease was nonexistent before the
"war on germs"? My claim is that in light of what is now known about the human
microbiome and its role in immune function, many common practices for
"fighting germs" can be predicted to have harmful effects, particularly in the
long run.

Do you have any reason to believe otherwise?

~~~
hga
Do you think these practices are _that_ effective? One of scythe's points is
that the ESKAPE bacteria are ubiquitous, in people and the environment.

Sure, taking an antibiotic deranges your microbiome, but doesn't it seem to
most of the time readjust?

My specific point is exactly what observed phenomena are you claiming this
explains? Until you have that, or a solid, _specific_ hypothesis leading to
bad specific things, I suspect the rest of us will continue to use antibiotics
when we get otherwise likely lethal infections. I brought up "microorganism-
involved disease" because I'm not aware of any significant changes in how they
work, play out in the human population, etc., besides the obvious.

~~~
tmoertel
Certainly, if you have an "otherwise likely lethal infection," take the
antibiotics. If they screw up your immune response down the road, it's still
better than dying now. I need to be clear that I'm not talking about this
specific case but the general practice of fighting what are believed to be
"bad germs" using techniques that can be expected to screw up the human
microbiome and, as a result, weaken the body's immune function, making it more
susceptible to exploitation by opportunistic pathogens.

As scythe wrote,

> That is to say: the six bacterial strains ... carrying the most severe
> antibiotic resistance and responsible for the worst infections are the very
> same strains present all around us naturally. However, in every case except
> S aureus, _infection is basically unheard of when an individual has a
> functioning immune system;_ they are all opportunistic pathogens. [Emphasis
> mine]

Right now, the emphasis in medical practice is on attacking the "bad germs."
What is mostly ignored is cultivating robust immune function, which as scythe
points out would mostly _prevent_ opportunistic pathogens from doing harm in
the first place. That's probably because until recently nobody knew much about
improving immune function. But now, with a better understanding of the human
microbiome, it's becoming hard to ignore that the techniques used to fight the
bad germs (e.g., broad-spectrum antibiotics) are probably also having harmful
effects on the human microbiome and, as a consequence, immune function. So the
short-term fix is likely to also cause long-term problems.

To give you an example of what I'm concerned about, let me share what happened
to my wife a few months ago. She had a rash on her lower leg, near her ankle,
and went to see her general practitioner. Her GP didn't know what the rash was
but nevertheless prescribed an anti-itch cream and -- surprise! -- a course of
antibiotics, "just in case." (It turned out that the rash was mild poison ivy,
so the antibiotics would have done nothing to help.) For many practicing
doctors, broad-spectrum antibiotics are used like this as a general
prophylactic for all manner of minor ailments. Lots of people are having their
microbiomes decimated for very little benefit.

> Sure, taking an antibiotic deranges your microbiome, but doesn't it seem to
> most of the time readjust?

By what mechanism would eliminated strains be repopulated? And if they weren't
repopulated and if your microbiome didn't "readjust," how could you tell?
After all, even if such derangements were permanent, we would not expect to
observe them until they were challenged by opportunistic pathogens and
exploited. It could be, therefore, that such derangements have an invisible
cumulative effect: the more screwed up your microbiome becomes the more at
risk you are, but unaware of it until you get sick.

------
emeerson
This looks like a viable research route? New pathway for eliminating bacteria
thats viral instead of antibiotic (fungal?) based:

[http://www.sciencedaily.com/releases/2012/07/120724104640.ht...](http://www.sciencedaily.com/releases/2012/07/120724104640.htm)

Can anyone speak to the validity or promise of such research?

~~~
hga
This is actually akin to a antibiotic, it's a protein, an enzyme that a
bacterophage virus produces to attack bacteria. See a bit more here:
[http://en.wikipedia.org/wiki/Lysin](http://en.wikipedia.org/wiki/Lysin) Also
see all the antibiotics that are peptides in the Wikipedia list:
[http://en.wikipedia.org/wiki/List_of_antibiotics](http://en.wikipedia.org/wiki/List_of_antibiotics)
A peptide is basically a small/short protein, by convention less than 50 amino
acids.

One issue which is noted in the Wikipedia article is that it's subject to
attack by the immune system. Maybe that won't be a big problem, or it can be
gimmicked, but it's still a big protein, would require topical or IV instead
of oral dosing, and it's not going to be able to get to a variety of places
that much smaller mold, indeed fungal produced antibiotics can get into.

~~~
memming
I'm curious as to why bacteria didn't evolve to resist Lysin?

~~~
hga
Well, perhaps some have (haven't looked at this closely), however, since in
nature the various types of it are only used by specific bacteriophages, i.e.
as I understand it they are or tend to be species specific, using a particular
one against other species of bacteria should be fruitful.

Then again, interspecies transfer of resistance through e.g. plasmids happens.

------
balsam
I was relieved the map showed Israel as a hub instead of India (which was
cited as the "source"). if you think Asiana scored it for "culturalism" then
this here could win the whole game. First disclosure: not an Indian.Second
disclosure: before clicking on the link I was expecting India or Africa. You
know, some tropical third way place? Maybe I just have the wrong kind of
paranoias. Bill Gates really needs to use his stature in India for this. If
anything is hard object versus immovable force, this is it.

~~~
hga
I follow this issue to some degree and unfortunately have to say this article
suggests more that it's a product of Britain's infamous and ancient
Antisemitism than something that reflects reality.

Or more precisely, it's politically necessary to not blame India, since that
country's reaction to the discovery of the terrifying New Delhi metallo-β-
lactamase (the first β-lactamase to incorporate a metal ion, it's _really_
good at what it does) was terribly counterproductive. See
[http://en.wikipedia.org/wiki/New_Delhi_metallo-beta-
lactamas...](http://en.wikipedia.org/wiki/New_Delhi_metallo-beta-lactamase_1)
for the basic story.

And I'm not at all surprised that by slight of hand they moved as much blame
to Israel as they could (what's in the article doesn't really support it).

~~~
cabalamat
> Britain's infamous and ancient Antisemitism

I'm British and it's not infamous enough for me to have heard of it.

~~~
hga
If you can't see it in your country's current actions, I don't know what to
say.

For the historical, start with e.g. this in 1144
[http://en.wikipedia.org/wiki/Blood_libel#Middle_Ages](http://en.wikipedia.org/wiki/Blood_libel#Middle_Ages)
and for more recent, read up on how at almost every turn Churchill's efforts
to help Jews during WWII were thwarted by those under him.

~~~
cabalamat
I don't deny that there is bigotry in Britain, including bigotry against Jews.
(Of course there is: there is bigotry everywhere).

What I do question is that there was/is more of it in Britain than in other
countries. For example, the part of Britain I live in (Scotland) is the only
European country never to have had state persecution of Jews.
([https://en.wikipedia.org/wiki/History_of_the_Jews_in_Scotlan...](https://en.wikipedia.org/wiki/History_of_the_Jews_in_Scotland))

> for more recent, read up on how at almost every turn Churchill's efforts to
> help Jews during WWII were thwarted by those under him.

If someone asked me to name a country that was "infamous" for anti-semitism
during WW2, I doubt if Britain is the one that would spring to mind. Nor would
it for most historians.

~~~
hga
Ah, I know nothing about Scottish Antisemitism or a lack thereof, and I
wouldn't be surprised to know it's different than England.

Your latter point is a bit of a cheap shot; of _course_ we all know which
country was "infamous" in WWII; what's interesting is the counties other than
that one. E.g. look at the percentage of Jews who survived in occupied ones,
factoring in the differences in the occupations. And which ones accepted
refugees and to what extent. Then there's the war policies, and there to a
very great extent the U.K. called the shots in the Western European Theater.
That's where I'm suggesting one look ... although of course it's not something
that can be quantified, seeing as it was the only combatant after the fall of
France.

~~~
cabalamat
> Your latter point is a bit of a cheap shot; of course we all know which
> country was "infamous" in WWII

Indeed. But your phrase was "Britain's infamous antisemitism". I was pointing
out that British antisemitism during WW2 was in fact not "infamous". Indeed,
if the worst thing that Britain did during WW2 wasn't harming Jews but not
helping them as much as some people in the UK government would have liked,
then they couldn't really have been very anti-semitic, could they?

In Britain, it is illegal to discriminate against someone because they are
Jewish, and has been for several decades. Furthermore, of Britain's two
largest political parties, one has a Jewish leader and the other did from
2003-2005; it is unlikely that either party would have done this if it thought
a Jewish leader would be an electoral liability, or if their rank-and-file
members disliked Jews. Are these the actions of a country "infamous" for
antisemitism?

------
meta-coder
"The [Indian] Union Health Ministry is considering a new National Antibiotics
Policy for the country to handle increasing antibiotics resistance in the
country."

News Article dated 27 July, 2013: [http://www.thehindu.com/sci-
tech/health/policy-and-issues/ne...](http://www.thehindu.com/sci-
tech/health/policy-and-issues/new-national-anitbiotics-policy-on-
anvil/article4958425.ece)

------
coldcode
Once people start to die in droves the obstacles to a cure will vanish.
Hopefully the people who can discover and manufacture the cure won't vanish
first.

------
saosebastiao
I have come across several doctors that have tried prescribing antibiotics for
preventative reasons to either myself or my family. How sad that it is the
people who understand this threat the most are the ones causing it.

I rarely resort to finger wagging and shaming for anything, but for
antibiotics misuse, not only do I feel it is appropriate, but I encourage
others to do the same. Veterinarians should get the same treatment, IMO.

------
derleth
If it gets bad enough, outpatient antibiotic use will be a thing of the past:
If you need antibiotics, you will be confined somewhere and your compliance
will be monitored. Laws will be passed to make non-compliance not simply a
crime, but effectively impossible. If worst comes to worst, the facilities
will be quarantined. There will be incinerators on site.

So, no, I don't worry about 'society'. Society has ways of defending itself.
However, when the notion of individual rights above all starts to bring about
an existential threat, something has to give.

