Antibiotic resistance: The last resort
nature.com
nature.com
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...)
As I understand the situation, antibiotic resistance isn't a generally useful adaptation - bacteria tend to lose it "in the wild". So prevalence of antibiotic resistant bacteria, in non human-to-human born diseases like Staph infections, is a somewhat direct result of maintaining a long term, antibiotic filled environment.
Antibiotics have changed the way we live, but the price of that change is that we have to invest in the arms race. We invest in all the other arms races, so why not this one?
Not necessarily a decisive pressure however. For bacteria which primarily "prey" on human beings this would be true. For bacteria which are primarily endemic to the environment, the loss of fitness involved in antibiotic vulnerability is something of a drop in the bucket. Remember this resistance has a cost in physiological adaptation too. These bacteria, like Staph, that might be "happy" to subside to resisting the common chemicals in a barnyard - unless we human produce an environment where tolerating antibiotic gives the organism a natural bridge to spread through - gigantic hospitals with filled with humans pumped with antibiotics or huge feed lots filled with similarly pumped animals "come to mind".
Can I reach you by email?
Speaking more generally, there is limited interest from big pharma in the use of natural or herbal products because they will have to spend a ton of money on clinical trials to prove effectiveness, but they won't get the patent protection necessary to recoup the cost of R&D, like they would with synthetic drugs.
Certain honeys -- and not particularly the more expensive ones -- are much more antibacterial in this regard than others.
(At least that's the way it was when I was still in the field.)
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...
Hospital acquired infection is a significant cause of death.
> In the United States, the Centers for Disease Control and Prevention estimated roughly 1.7 million hospital-associated infections, from all types of microorganisms, including bacteria, combined, cause or contribute to 99,000 deaths each year.
> In Europe, where hospital surveys have been conducted, the category of Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year.
(http://en.wikipedia.org/wiki/Hospital-acquired_infection)
These are just nosocomial (hospital acquired) and not necessarily antibiotic resistant.
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), "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....
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.
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.)
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.
At the VERY least I urge you to design novel experiments and post them publicly.
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.
> That might be, shall we say, a somewhat short term
problem as the population is culled of less hardy individuals
Anyway silly question. If the bacterias are so well at adapting to antibiotics, can't we create some kind of mold that can adapt to the bacteria? E.g. take bacteria A spread it to N + 1 Paetri dishes, put some mold in N dishes and select which is better. Then take the last remaining dish and create a new set of N+1 bacteria dishes.
In comparison, part of the reason we're in this situation in the first place is because doctors can't even be bothered to figure out which antibiotic is suitable, or whether or not you actually have a bacteria infection, but often just prescribes first-line antibiotics and tells you to come back if you're still ill afterwards. That means 5-10 minutes per patient many places.
If we were to try to switch to bacteriophages, on the other hand, it'd mean blood tests and lab work to identify the specific infection and strain for every patient, with resulting massive cost increases.
In it's current state, it's a last way out, but it's far away from being a viable large scale replacement for antibiotics.
WRT to the first problem, starting in 1995 I got recurrent sinus infections (which are now mostly prevented with a couple of nasal sprays). A sinus biopsy is not practical, instead my doctor, knowing what locally worked, gave me one particular antibiotic. Later a standard formulation of that plus an anti-β-lactamase drug. Then the one that still works (a different β-lactam family), but I need 30 days of it.
When I was unemployed and only had catastrophic medical coverage I got a full course from samples of a new, lipophillic drug that builds up a concentration in your fat and you therefore don't need to take it for so long, and the constant dose no doubt helps. But that one failed for the next sinus infection and I was back to the 30 day one....
Errm, when it's pretty clear the patient has a bacterial infection, why isn't it often a best practice to give a first line drug while doing a culture? Strep throat is the classic example I can think of from when I and my siblings got that in the '70s ... of course, although I don't know if it was realized by then, giving an antibiotic for it is mostly prophylactic, to avoid rheumatic fever. I have a very good friend who's about a decade older than me, when she got that her mother completely freaked out because prior to right then it was a death sentence. Fortunately penicillin was just making it out into civilian use....
I meant it largely to contrast it with bacteriophages, where we don't get the choice. Antibiotics "won out" to a large extent because alternatives like bacteriophages are tremendously more expensive and complicated compared to the practice of handing out antibiotics without blood work. If we took all available precautions to prevent resistance, then we'd face much reduced risks of antibiotics resistance, but the cost gap would reduce accordingly as well.
Antibiotics are so important exactly for the reasons that give us resistance: It is cheap, easy and fast for all but the unfortunate cases that run into resistance.
> Errm, when it's pretty clear the patient has a bacterial infection, why isn't it often a best practice to give a first line drug while doing a culture?
It often may be. The problem are the cases where antibiotics are given when it isn't even clear if its a bacterial infection - in the UK for example doctors will often give antibiotics "just in case". The second problem is that this means that antibiotics will quite often also be given in situations where the bacteria in question will not respond to the treatment, or will survive in sufficient number to cause the infection to rebound and leave the patient walking around potentially spreading an infection with increased resistance to the first line antibiotics.
Again, it is a tradeoff that sometimes is necessary, and very often the best recourse for that specific patient. But that doesn't mean it doesn't contribute to increasing overall levels of antibiotics resistance and that some of these decisions negatively affect society as a whole.
Incidentally if/when we can find technologies to speed up precise tests for specific strains, bacteriophages might become suitable for more situations and we might be able to limit use of antibiotics for the situations where we can't risk waiting.
edit: It is my belief that most problems don't get treated as "real" in people's minds unless they are two degrees of separation or less from someone who is affected.
I've posted this clip before, but in case you missed it:
(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).
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.)
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?
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.
I think this effect is the extremely under appreciated benefit of sex/exchanging dna.
I've heard suggestions that the mutation rate can go up in a high-stress environment, perhaps that could be related?
I hope the HN research effect kicks in and someone finds and summarizes the research on these questions.
The nastier stuff, like β-lactamases---enzymes that destroy the β-lactam ring that is the "active ingredent" of so many antibiotics ... and that it's used by so many families that humans can tolerate is telling---are obviously a lot more sophisticated. Bacteria developed them to compete with the molds that produce β-lactam antibiotics, and they spread from one species to another, especially in plasmids as the article notes.
A great deal of this is not new mechanisms of resistance being developed, but long existing ones becoming prevalent. Somewhat like in the good old days when a drug company could make its money back bring an antibiotic to market, and scouring the globe for molds that produced ones, improper use of antibiotics (e.g. not switching to one of different mechanism quickly enough, especially likely in places like India where they're in practice available over the counter) plus widespread global travel is allowing the best mechanisms to survive and sort of thrive.
Not thrive in most environments of course, just in humans who are under the selection pressures of antibiotics.
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.
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.).
"[...] antibiotics are readily available over the counter at pharmacies...."
"Last week, physicians moved a step closer to their goal when India’s drug regulators announced a plan that would put tight restrictions on the sale of antibiotics. Carbapenems and many other antibiotics are already on a list of 536 drugs in India that require a prescription. But studies have shown that such drugs are easy to purchase at retail pharmacies without a physician’s signature...."
This article from a bit less than a year ago then says the new measures will be adding red labels and surprise inspections....
Lots more hits where that came from, including plenty from India.
And the usual suspect would scream bloody murder ... it's a difficult question of more people dying today to prevent even more people dying tomorrow, something people are generally bad at dealing with until the 11th hour when its often too late.
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."
We'll probably end up using phages because we won't have any other choice. But that's not a step forward for patients.
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.
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.
EDIT: I should say I didn't follow his work that closely, so it's possible there were efficacy problems as well.
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.
Hmmmm. Maybe so, but would you inject them?
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.
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?
Chronic diseases cannot generally be "cured", just controlled, so patients need a lifetime supply of a drug.
A new antibiotic will only be used in the direst of cases, like vancomycin as mentioned in the article.
It costs so bloody much to get a drug to market that drug companies tend to chase the former, where they can in theory get their money back (that's actually not tending to happen overall), whereas the latter could bankrupt them. Asking the government or charities to play this game is asking for politics to further enter into it, the outcomes are not likely to be good.
"Asking the government or charities to play this game is asking for politics to further enter into it, the outcomes are not likely to be good."
I'm curious where this die-hard free-market willful blindness comes from. I object to the categorical classification of government or charity being bad choices to solve problems.
The nature of the specific market under discussion makes all the difference in the world. The nature of the administrative path from funding to research & development also makes a difference. There can be efficient allocation of funds in government and in private sector charities, just as there can be inefficient allocation of funds due to bad management in private companies devoted to solving the same problems.
Free marketeers have effectively redefined "government run program" to mean inefficient... it may be that most of the time, but there is nothing inherent about government programs that demands inefficiency. There's a similar stigma regarding charity. Those are almost effects of free-market thinking: if everyone is convinced that government and charity are poor ways to solve any problem, then government and charity are left with incompetent administrators, bloated management structure, and poor oversight.
Since this problem is identified as one that the private commercial sector is poorly motivated to solve, the question is not whether public sector or charity should attempt to tackle the problems -- it should -- but how to structure charity or government programs so as not to waste the money they are given to address the problem.
On the most general principles, I claim politics are a given in organizations of the scale we're talking about. My special claim about governments and charities is that for-profit companies have a governor in that if they don't make a profit, they'll suffer and eventually die. WRT to my testing point, I also don't want the same entity having a large hand in both developing and testing drugs. I'd also want to look at the current and past roles governments have had in pure drug development; it certainly can do amazing things like the wartime push of penicillin mass production, then again that's not the sort of problem we're having today with antibiotic resistance.
"Since this problem is identified as one that the private commercial sector is poorly motivated to solve...."
Which has a whole lot to do with the government's regulation of pretty much everything involved in getting a drug to market. Not everything, certainly, it's hard to develop these sorts of drugs, and I think its telling how many of the families use β-lactam rings. So I claim that changes in laws and regulations are in theory a very fruitful avenue. In theory because the demonization of "profit", especially in the context of saving lives, makes promises a government makes today highly suspect, "I am altering the deal. Pray I don't alter it any further."
1. Government intervention screwing up what would work in a purely free market.
2. Markets that free enterprise is not equipped to handle. Massive front-end costs combined with unpredictable or insufficient future revenue (for instance, reducing or eliminating externalities in a way that the company can't capitalize on renders something unworkable for the free market).
3. Markets that have a pathological condition where they are inelastic and when there are less-desirable substitute goods one of which is vastly more profitable.
4. Markets that are monopolies or oligopolies: where there is insufficient competition.
Is it even productive to engage in a discussion focusing on category 1, when pharma has issues in all four categories, and reducing government regulation in any way even if it's merely to reduce unnecessary up-front drug development costs (which I agree is a noble goal) is likely to make some of those other pathologies worse?
edit to reduce clutter: fair enough.
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.
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?
Governments could refuse entry to people who've visited that country.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Developm...
Based on the seriousness of the infection being targeted, the FDA is creating accelerated approval pathways. There has already been some discussion about guaranteeing a certain amount of profit for the pharmaceutical company once it hits the market.
It's a start.
I'm curious to know what diseases you're talking about here. I don't see much improvement in this area at all.
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.
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."
i.e. most people think, just wait a few years until the scientists develop a better antibiotic. Cat and mouse.
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.
This may of course be totally silly, but I'm just wondering if anyone has done any research on it.
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.
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.
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.
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.
This is a grander version of the hygiene hypothesis (https://en.wikipedia.org/wiki/Hygiene_hypothesis), but unlike it I don't see a phenomena to explain.
Do you have any reason to believe otherwise?
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.
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.
http://www.sciencedaily.com/releases/2012/07/120724104640.ht...
Can anyone speak to the validity or promise of such research?
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.
Then again, interspecies transfer of resistance through e.g. plasmids happens.
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... 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).
I'm British and it's not infamous enough for me to have heard of it.
For the historical, start with e.g. this in 1144 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.
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...)
> 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.
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.
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?
It's just that Israel is technologically advanced enough to actually track these bugs so there is data to map.
Other countries (India) are much larger hubs, but they don't check for it so there is no data to use.
News Article dated 27 July, 2013: http://www.thehindu.com/sci-tech/health/policy-and-issues/ne...
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.
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.