11 ms·

Antibiotic resistance: The last resort

200 points by dn2k 13y ago

jivatmanx 13y ago
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?
- hga 13y ago
  And your single first sentence (this was drafted before you added your second paragraph) hints as to why: 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.
  - harshreality 13y ago
    I absolutely agree that the financial incentives are mismatched, with private companies less interested in trying to cure or improve underlying medical problems than in treating/controlling symptoms. "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.
    - hga 13y ago
      When you talk about efficiency you're going off on a tangent I'm not intending; in this case, I'm much more worried about political choices on what approaches and drugs to pursue, and politics messing with the safety and efficacy testing. Also, anyone thinking there is anything like a "free-market" pharmaceuticals is simply not paying attention. 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."
      - harshreality 13y ago
        So, continuing on the meta track, there are several cases when the private sector fails, which I'll try to categorize: 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.
- etiam 13y ago
  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 13y ago
    "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 13y ago
      > 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.
      - 13y ago
- yk 13y ago
  Markets are quite bad at developing any kind of reserves. So in the case of antibiotics: we have the antibiotics we need at the moment ( at least mostly). A new antibiotic would be quite expensive to develop, and then it would just sit on a shelf. Thinking about it, it is quite the same as the banking crisis in 2008, there was no secondary banking system, because that would operate at higher cost and therefore get kicked out of the market.
- refurb 13y ago
  The FDA is already creating incentives for antibiotic research. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm317207.htm 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.
- tsotha 13y ago
  >The lack of advancement in antibiotics is a stark contrast to the recent improvements in treatments for so many chronic diseases. I'm curious to know what diseases you're talking about here. I don't see much improvement in this area at all.
w1ntermute 13y ago
> 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.).
- hga 13y ago
  A quick check with Google (indian pharmacy antibiotics) confirmed my understanding that they're basically unregulated (http://www.nature.com/news/india-moves-to-tackle-antibiotic-resistance-1.11392 http://www.nature.com/news/india-moves-to-tackle-antibiotic-...): "[...] 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.
- cageface 13y ago
  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 13y ago
    How on Earth can this happen? Doesn't Vietnam have trained doctors? This practice is ridiculously dangerous? Why?
    - manmal 13y ago
balsam 13y ago
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 13y ago
  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-lactamase_1 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).
  - cabalamat 13y ago
    > Britain's infamous and ancient Antisemitism I'm British and it's not infamous enough for me to have heard of it.
    - hga 13y ago
      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.
      - 13y ago
fragsworth 13y ago
> 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 13y ago
  Yes. When I read that I thought "so, over-hyped and not really a problem, then".
  - jurassic 13y ago
    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 13y ago
      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 13y ago
        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.
DanBC 13y ago
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-superbug-idUSTRE76A0YO20110711 http://www.reuters.com/article/2011/07/11/us-gonorrhoea-supe...) 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 13y ago
  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 13y ago
    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.
plg 13y ago
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 13y ago
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.
- pohl 13y ago
  Reintroduce them where? Into my abdomen during my appendectomy?
  - joshuak 13y ago
    Exactly so. Maybe, maybe not during surgery (depending on how benign we're talking), but perhaps at the first sign of non-responsive infection. Stop the IV antibiotics, and start up the 'good' bacteria drip. This may of course be totally silly, but I'm just wondering if anyone has done any research on it.
    - deleted 13y ago
      [deleted]
- hga 13y ago
  We've been doing the probiotic thing for a long time, I can remember being fed not in the least tasty bacteria granules stored in foil wrappers in the fridge in the late '60s. But outside of the gut how could you do this? Skin isn't going to work, not with it being exposed to zillions of bacteria in the wild. Of course, those should be wild-type and not necessarily antibiotic resistant.
- LisaG 13y ago
  That's interesting. We also could revive phage therapy which uses bacteriophages (viruses that replicate in bacteria). http://en.wikipedia.org/wiki/Phage_therapy http://en.wikipedia.org/wiki/Phage_therapy
scythe 13y ago
>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 13y ago
  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 13y ago
    Would introducing probiotics after disinfection do anything?
    - LaGrange 13y ago
      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).
  - ams6110 13y ago
    As a surgeon I know says, "the last place you want to be if you're sick is in a hospital."
timr 13y ago
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/SB10001424127887323975004578499324161473326.html http://online.wsj.com/article/SB1000142412788732397500457849...)
- joe_the_user 13y ago
  I believe it shows the general insanity of the whole health and food-production systems. 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.
  - timr 13y ago
    Yes and no. We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence. So while we can mitigate antibiotic resistance by reducing use, we'll only slow down the problem. 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?
    - joe_the_user 13y ago
      "We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence." 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".
jechmu 13y ago
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 13y ago
  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.
chestnut-tree 13y ago
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 13y ago
  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 13y ago
    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 13y ago
      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.
emeerson 13y ago
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.htm http://www.sciencedaily.com/releases/2012/07/120724104640.ht... Can anyone speak to the validity or promise of such research?
- hga 13y ago
  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 13y ago
    I'm curious as to why bacteria didn't evolve to resist Lysin?
    - hga 13y ago
      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.
zw123456 13y ago
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 13y ago
  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."
tmoertel 13y ago
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 13y ago
  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.
saosebastiao 13y ago
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 13y ago
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.
meta-coder 13y ago
"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/new-national-anitbiotics-policy-on-anvil/article4958425.ece http://www.thehindu.com/sci-tech/health/policy-and-issues/ne...
coldcode 13y ago
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.

200 points by dn2k 13y ago

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?

hga 13y ago
And your single first sentence (this was drafted before you added your second paragraph) hints as to why: 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.
- harshreality 13y ago
  I absolutely agree that the financial incentives are mismatched, with private companies less interested in trying to cure or improve underlying medical problems than in treating/controlling symptoms. "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.
  - hga 13y ago
    When you talk about efficiency you're going off on a tangent I'm not intending; in this case, I'm much more worried about political choices on what approaches and drugs to pursue, and politics messing with the safety and efficacy testing. Also, anyone thinking there is anything like a "free-market" pharmaceuticals is simply not paying attention. 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."
    - harshreality 13y ago
      So, continuing on the meta track, there are several cases when the private sector fails, which I'll try to categorize: 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.
etiam 13y ago
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 13y ago
  "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 13y ago
    > 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.
    - 13y ago
yk 13y ago
Markets are quite bad at developing any kind of reserves. So in the case of antibiotics: we have the antibiotics we need at the moment ( at least mostly). A new antibiotic would be quite expensive to develop, and then it would just sit on a shelf. Thinking about it, it is quite the same as the banking crisis in 2008, there was no secondary banking system, because that would operate at higher cost and therefore get kicked out of the market.
refurb 13y ago
The FDA is already creating incentives for antibiotic research. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm317207.htm 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.
tsotha 13y ago
>The lack of advancement in antibiotics is a stark contrast to the recent improvements in treatments for so many chronic diseases. I'm curious to know what diseases you're talking about here. I don't see much improvement in this area at all.

w1ntermute 13y ago

> 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.).

hga 13y ago
A quick check with Google (indian pharmacy antibiotics) confirmed my understanding that they're basically unregulated (http://www.nature.com/news/india-moves-to-tackle-antibiotic-resistance-1.11392 http://www.nature.com/news/india-moves-to-tackle-antibiotic-...): "[...] 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.
cageface 13y ago
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 13y ago
  How on Earth can this happen? Doesn't Vietnam have trained doctors? This practice is ridiculously dangerous? Why?
  - manmal 13y ago

balsam 13y ago

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 13y ago
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-lactamase_1 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).
- cabalamat 13y ago
  > Britain's infamous and ancient Antisemitism I'm British and it's not infamous enough for me to have heard of it.
  - hga 13y ago
    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.
    - 13y ago

fragsworth 13y ago

> 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 13y ago
Yes. When I read that I thought "so, over-hyped and not really a problem, then".
- jurassic 13y ago
  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 13y ago
    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 13y ago
      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.

DanBC 13y ago

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-superbug-idUSTRE76A0YO20110711 http://www.reuters.com/article/2011/07/11/us-gonorrhoea-supe...) 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 13y ago
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 13y ago
  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.

plg 13y ago

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 13y ago

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.

pohl 13y ago
Reintroduce them where? Into my abdomen during my appendectomy?
- joshuak 13y ago
  Exactly so. Maybe, maybe not during surgery (depending on how benign we're talking), but perhaps at the first sign of non-responsive infection. Stop the IV antibiotics, and start up the 'good' bacteria drip. This may of course be totally silly, but I'm just wondering if anyone has done any research on it.
  - deleted 13y ago
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hga 13y ago
We've been doing the probiotic thing for a long time, I can remember being fed not in the least tasty bacteria granules stored in foil wrappers in the fridge in the late '60s. But outside of the gut how could you do this? Skin isn't going to work, not with it being exposed to zillions of bacteria in the wild. Of course, those should be wild-type and not necessarily antibiotic resistant.
LisaG 13y ago
That's interesting. We also could revive phage therapy which uses bacteriophages (viruses that replicate in bacteria). http://en.wikipedia.org/wiki/Phage_therapy http://en.wikipedia.org/wiki/Phage_therapy

scythe 13y ago

>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 13y ago
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 13y ago
  Would introducing probiotics after disinfection do anything?
  - LaGrange 13y ago
    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).
- ams6110 13y ago
  As a surgeon I know says, "the last place you want to be if you're sick is in a hospital."

timr 13y ago

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/SB10001424127887323975004578499324161473326.html http://online.wsj.com/article/SB1000142412788732397500457849...)

joe_the_user 13y ago
I believe it shows the general insanity of the whole health and food-production systems. 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.
- timr 13y ago
  Yes and no. We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence. So while we can mitigate antibiotic resistance by reducing use, we'll only slow down the problem. 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?
  - joe_the_user 13y ago
    "We do overuse (and mis-use) antibiotics, but as long as we use them at all, bacteria will have an evolutionary pressure to adapt to their presence." 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".

jechmu 13y ago

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 13y ago
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.

chestnut-tree 13y ago

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 13y ago
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 13y ago
  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 13y ago
    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.

emeerson 13y ago

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.htm http://www.sciencedaily.com/releases/2012/07/120724104640.ht... Can anyone speak to the validity or promise of such research?

hga 13y ago
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 13y ago
  I'm curious as to why bacteria didn't evolve to resist Lysin?
  - hga 13y ago
    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.

zw123456 13y ago

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 13y ago
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."

tmoertel 13y ago

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 13y ago
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.

saosebastiao 13y ago

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 13y ago

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.

meta-coder 13y ago

"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/new-national-anitbiotics-policy-on-anvil/article4958425.ece http://www.thehindu.com/sci-tech/health/policy-and-issues/ne...

coldcode 13y ago

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.