Current Antibiotics Risk Becoming Useless.

[Big Orange]

Here's something to give you sleepless nights:

Health chief warns: age of safe medicine is ending
Antibiotic crisis will make routine operations impossible and a scratched knee could be fatal

The world is entering an era where injuries as common as a child's scratched knee could kill, where patients entering hospital gamble with their lives and where routine operations such as a hip replacement become too dangerous to carry out, the head of the World Health Organisation (WHO) has warned.

There is a global crisis in antibiotics caused by rapidly evolving resistance among microbes responsible for common infections that threaten to turn them into untreatable diseases, said Margaret Chan, director general of the WHO.

Addressing a meeting of infectious disease experts in Copenhagen, she said that every antibiotic ever developed was at risk of becoming useless.

The Independent


People are blaming various sources for this looming crisis (such as world travel, hospital hygiene and the almost industrial overuse of antibiotics on farm animals, etc) however hopefully something like viral phages could help us out and people in general should apply common sense (like not take antibiotics for trivial stuff), otherwise we'll have health set back by a century.

[mr friendly guy]

How can people take antibiotics for trivial stuff without a doctor's prescription? They wouldn't need common sense, the Doctor should exercise clinical judgement. At least thats how it works in Australia. I am aware that countries such as cough Indian cough antibiotics can be brought over the counter. Madness. Of course since most of the antibiotics are prescribed to animals without a doctor's prescription, I guess we can't fault the humans taking them too much.

I also find it interesting the statistic about the EU and antibiotic resistant bugs. I once saw a patient who was hospitalised in Germany and brought back an ESBL bacteria, I think it was E.coli and that was the first time I ever saw such a strain. He was resistant to even the carbapenems. Fortunately we had a secret weapon. Colistin. A drug used in detergents IIRC, which was replaced eventually in clinical practice by the less toxic gentamicin. Any doctor can tell you gentamicin itself is quite nephrotoxic and ototoxic so imagine how bad colistin must be. Now here comes the unfortunate part. Colistin started killing his kidneys, so we had to stop and accept that this bacteria will be hanging around. Its ze Germans fault.

How does the EU handle antibiotic resistant bacteria? When we had an outbreak of VRE in WA, Royal Perth Hospital instituted extensive measures to beat it. So once you find it, eradicate it before the species has a chance to further evolve and develop resistance. Its standard protocol in Western Australian hospitals to isolate and eradicate MRSA (even if the patient is hospitalised for a totally unrelated complaint), and infectious diseases are consulted about resistant bacteria. Rules of prescription of antibiotics are employed, so you need the approval from the Infectious disease department to prescribe certain antibiotics (except for certain conditions). Perhaps some of our European members can shed light on this matter.

[Sea Skimmer]

Lots of doctors prescribe antibiotics for common viral colds if people ask hard enough and lots of idiot mothers shop around for doctors who will prescribe antibiotics for everything a child gets, at least in the US. This is then compounded by people ceasing to take the pills because they ‘felt better’. Meanwhile I think on average less than two new antibiotics are approved each year for human use and most are just variations on existing compounds rather then something entirely new.

[evilsoup]

I remember hearing something about this a while ago, on the BBC: the pharmacutical companies don't research new antibiotics because they know that doctors will just hold it in reserve, like mr friendly guy's example. So this is capitalism in action.

Does anyone know how much it costs to research a new antibiotic? The best way around this (short of smashing the system, eating the rich and stealingnationalising their stuff) would be for governments to offer prizes for antibiotics... but I don't know what the price-range would be.

[K. A. Pital]

The good idea would be to stop prescribing antibiotics for common colds, like they often do here in Germany. I never saw that happen so massively in Soviet Russia.

[Sea Skimmer]

Does anyone know how much it costs to research a new antibiotic?

In the early 2000s I read that the figure was about 2 billion USD and rising fast. The 'average' new drug cost about 500 million in R&D at the same time. Antibiotics are expensive to research because you have to test them against such a wide range of conditions and germs and specifically seek out the antibiotic resistant germs to see if your new drug has any advantage. This is unlike most drugs which are targeting one specific thing. Also the scary thing is, between 1962 and 2000 no completely new type of antibiotic was discovered at all. That wasn't for lack of trying, its just very hard to do.

The best way around this (short of smashing the system, eating the rich and stealingnationalising their stuff) would be for governments to offer prizes for antibiotics... but I don't know what the price-range would be.

Governments already put a fair bit of money into research like this, certainly they could do more. However for the moment we'd have a lot more hope trying to use existing drugs more effectively then hoping to discover new types, we already have thousands of different antibiotics. Even a massive increase R&D money won't save us if we just keep using them stupidly. By many accounts we also just need major reform in the slow manner in which the US FDA operates, since the considerable majority of the worlds twenty largest pharmaceutical companies are based in the US, and once you get below the top 20 the scale of the operations drops off rapidly. It will really help if China can begin doing credible work in this field.

[evilsoup]

Bloody hell that's even more than I assumed.

Of course you are right that the main thing is to use what we have less frivolously. Get rid of factory farming for animals, for example (as if we needed more reasons to get rid of that particular horrorshow). Can't really speak for doctors proscribing stuff unneccesarily, but I have witnessed plenty of people not completing their courses of antibiotics because 'oh now I feel better'.

[RIPP_n_WIPE]

This is one of the many reasons I do not take medication unless my life is absolutely in danger or infection risks permanent injury. Vitamins, good diet and water. I honestly don't remember the last time I took a pill that wasn't a dietary supplement. I have an immune system evolved to adapt to such things. Now my fellow humans are pushing bacterial evolution and putting me at risk. Thanks a lot assholes...

[Sea Skimmer]

Bloody hell that's even more than I assumed.

Of course you are right that the main thing is to use what we have less frivolously. Get rid of factory farming for animals, for example (as if we needed more reasons to get rid of that particular horrorshow). Can't really speak for doctors proscribing stuff unneccesarily, but I have witnessed plenty of people not completing their courses of antibiotics because 'oh now I feel better'.

I'm not sure how much the huge animal market actually matters, lots of focus it put on that issue but the actual range of antibiotics being used for that purpose is limited. Also something to consider is the hospital environments themselves. We don't just get the super germs from antibiotics, we also get them from the massive use of disinfectants on everything. Surgical tools themselves are sterilized by high pressure and high heat processes, but everything else is being scrubbed down with the same couple cleaning compounds over and over and over again... this issue is kind of mind boggling to think about. If we can't use cleaning products WTF will we do, boil specific rooms with steam once a day?

[cosmicalstorm]

Chilling news indeed. I know a lot of people who sleep around and then "pop a pill" if something happens, this is going to be bad once it starts happening to common STD's. Are there any other treatment alternatives to severe bacterial infections?

[Sea Skimmer]

No for the moment antibiotics are the only way to directly target bacteria in the human body. Any other treatment is just means of supporting the body's natural defenses. Keep in mind that antibiotics is a pretty wide classification of drug. Some don't even kill the bacteria for example, they just stop its multiplication. Some types chemically burn holes in bacteria cells and burst them as an extreme kind of killing, and other kinds target bacteria internally and disrupt formation of proteins ect... I'm sure more fundamental variation exists that's just what I know easily.

Now what might give some long term results is research being done on attempting to exploit the mutations of the bacteria that make them resistant as a means of targeting drugs that kill them. I don't know if any drug for this purpose has been approved though, I don't think it has been. Some study is also being given to making viruses that would attack specific bacteria, they exist in nature, single cell parasites that do the same, and simply finding less harmful bacteria that can out compete more harmful types and might be easier to kill in turn with antibiotics . So... avenues of research exist but its difficult. I think the safety issues with these approaches are more then obvious!

[mr friendly guy]

Chilling news indeed. I know a lot of people who sleep around and then "pop a pill" if something happens, this is going to be bad once it starts happening to common STD's. Are there any other treatment alternatives to severe bacterial infections?

Most of the "superbugs" we hear about aren't STDs. MRSA (sorry "mercer" for the Americans ) is a skin infection, VRE is a gut infection, ESBL E.coli usually is a urine, and the article mentions K.pneumoniae which is gut, urine, chest infection. So it hasn't happened (or at least not as bad) for STDS so far. Most probably because the other infections are more common than STDs so have been subjected to more antibiotics.

As to alternatives to bacterial infection, in some cases you can surgically remove the infected part. For example osteomyelitis sometimes surgeons remove the infected bone and we continue antibiotics after. However thats quite a specific case and I don't think its what you are specifically asking for. You can also "boost" the immune system with drugs like Colony Stimulating Factor, which are sometimes used in chemo patients with infections after chemo has weaken their immune system. I am unaware of it being tested in a patient who can still mount an immune response, so we have no idea how well it would work in someone with an antibiotic resistant bacteria. It most probably will never be tested since its quite an expensive drug.

Ultimately the way to do this is to better manage antibiotics. This includes
1. Prescribing only when necessary - ie the doctor needs to exercise proper clinical judgement. Australia restricts in hospital as I mentioned above. Other countries like China are also instituting policies to restrict it.


2. Preventing over the counter purchase of antibiotics - India I am looking at you.

3. Changing the antibiotics from a broad spectrum (eg 3rd generation cephalosporin, carbapenems) to an antibiotic with less spectrum (eg penicillins) once sensitivities (ie which antibiotics the bacteria is vulnerable to) are known.

4. Patients must finish the course of antibiotics. Not finish when they feel better. Finish the prescription as guided by the doctor. The full lot. This is particularly a problem in uneducated parts of Asia with TB, where the course can last for 6 months. Its very difficult managing non compliance with medications, but perhaps better education may help with the services to follow up (ie get to the patient at home and nag nag nag, check up that they are taking the medications).

5. We need to look into prescription of antibiotics into lifestock and see if we can do anything there.

[mr friendly guy]

Oh the other thing I forgot to add is consider is in some cases we can bring back older antibiotics. Whats old is new again. The aforementioned colistin. In the case I mentioned it didn't work because it was nephrotoxic and it definitely isn't worth it to kill a person's kidneys and subject them to dialysis. However.... if that person was already on dialysis then it really doesn't matter whether we give them nephrotoxic drugs anyway. The metaphorical horse has already bolted.

Edit - theoretically you could also switch antibiotics for different indications to buy time. For example gentamicin is usually given for severe urine infections (usually when it becomes sepsis, ie blood poisoning) or gram negative infections. It used to be administered in pneumonia, yet I have only seen it used once for that, but according to my consultant he saw it more frequently back in the day. Perhaps this alternating might work. Obviously it would need to be instituted in coordination between hospitals in a country, and I will leave it to experts to think whether this will work. Certainly from an evolutionary point of view this should buy us time, the same way we alternated insecticides to prevent resistance among insects.

[Sea Skimmer]

I recall reading some research which indicated, that at least with certain germs if we removed an antibiotic from production and use, it could actually regain significant effectiveness within a few years. However once used again, germ immunity would return much more quickly then it originally formed. With 5,000 antibiotics around this might be useful, at least as a cushion.

I think part of the issue with India is, besides being run by a less then effective government, most people can't afford doctors visits and government run clinics are very few and far between. They are more afraid of mass disease outbreaks then long term problems.

[mr friendly guy]

I recall reading some research which indicated, that at least with certain germs if we removed an antibiotic from production and use, it could actually regain significant effectiveness within a few years. However once used again, germ immunity would return much more quickly then it originally formed. With 5,000 antibiotics around this might be useful, at least as a cushion.

I think part of the issue with India is, besides being run by a less then effective government, most people can't afford doctors visits and government run clinics are very few and far between. They are more afraid of mass disease outbreaks then long term problems.

I remember hearing about the same thing with insects. Which is why I think this is a measure that will buy us time at best, but something is better than nothing. I don't doubt we have lots of antibiotics, some of which I most probably haven't heard of, but there are not really that many classes of antibiotics themselves, and sometimes there is a class resistance with bacteria. We may end up combining classes of antibiotics to treat things which previously only required one or two antibiotics, like we do for TB.

[Tsyroc]

2. Preventing over the counter purchase of antibiotics - India I am looking at you.

Mexico allows this too. My uncle has gone down there to buy ciprofloxacin just to have on hand for when he feels sick.

My dad also bought a course of levofloxacin for one of our dogs in Mexico. It was cheaper than buying it in the US. He did have a prescription for the dog to be on the drug and as a pharmacist clearly knows not to stop before the antibiotic course is finished.

[Guardsman Bass]

I recall reading some research which indicated, that at least with certain germs if we removed an antibiotic from production and use, it could actually regain significant effectiveness within a few years. However once used again, germ immunity would return much more quickly then it originally formed. With 5,000 antibiotics around this might be useful, at least as a cushion.

That's what I've read as well. The heavily antibiotic resistant strains only tend to be competitive when there's over-use of antibiotics going on with patients. If we better manage the antibiotics, the vulnerable strains tend to quickly replace the antibiotic resistant ones because antibiotic resistance has a fairly steep "cost" in terms of fitness.

Here is an abstract from 2010.

[Xon]

I'm not sure how much the huge animal market actually matters, lots of focus it put on that issue but the actual range of antibiotics being used for that purpose is limited. Also something to consider is the hospital environments themselves.

linky

The World Health Organisation (WHO) says drug use in farm animals plays a 'significant role' in spreading antibiotic-resistant salmonella and campylobacter infections in humans while EU food safety officials say it could also be a source of some antibiotic-resistant strains of MRSA and E.coli - both potentially life-threatening infections - and, in the case of E.coli, a new highly resistant type of which was recently found on a large number of dairy, pig and poultry farms in England and Wales.

Dutch scientists recently went as far as estimating that between a third and one half of resistance in human infections in the Netherlands originated from farm animals. Although the figure is estimated to be lower in the UK, agriculture is believed to now account for the majority of antibiotic-resistance in food poisoning cases.

It's not hard to find other references and quotes around. It's only very recently that it's become a easily noticable problem. Many of the antibiotics between farm use and human use are very similar, and this is not a good thing.

[mr friendly guy]

According to the article Xon linked to antibiotics used in farming include cephalorsporins and tetracyclines, although it didn't mention which ones. Cephalorsporins are quite broad spectrum, in Australia they cover a lot of things like Strep, Staph, and some gram negative bacteria as well. Tetracyclines are also reasonably broad spectrum, covering things like "atypical" pneumonia. So its not like they are using targeted antibiotics, its reasonably broad spectrum.

[Xon]

Either way, it is a good case on to not frivolously use antibiotics everywhere. The only saving grace is the antibiotics commonly used in animal raising are not the various holdout antibiotics used for humans. But, continuing to select for resistance to common antibiotics means those common antibiotics become less useful, that is the simple truth of it.

abc.net.au article on the subject from 1999

The emergence of vancomycin-resistant Enterococcus (VRE) may also be related to the use of Avoparcin as an animal growth promoter. "There is fairly convincing evidence in Europe that the VRE germ probably developed in animals, pigs and chickens in particular, and this was acquired by the general population through the food chain,"

another from 2011

Dr Gottleib says the risk of humans eating animals that have been fed antibiotics is still unknown.

But he says the link between human resistance and eating animals pumped with antibiotics is increasing.

"The best example has recently happened in The Netherlands, where they looked at a lot of their chicken meat, retail chicken meat, and they were able to pick up these very resistant E. coli (Escherichia coli) strains, which are resistant to some of the last line antibiotics in about 80 per cent of their chickens, and clearly related to use of those antibiotics in the food chain.

"These were then linked very clearly to the same strains occurring in humans. So there is a very close link to it.

"We're becoming increasingly convinced that antibiotic use in food producing animals eventually leads to resistance in humans as well."

If we can't use cleaning products WTF will we do, boil specific rooms with steam once a day?

There is some stuff where it comes quite close to that to contain/kill it. Very powerful detergents are hard for bacteria to evolve defenses against. As rather than gum up/short circuit the cells of a bacteriam, detergent tend to chemically rip them apart. Powerful detergents can also be carcinogenic, and really quite horrible to be exposed to.

[mr friendly guy]

I just like to clarify that when I said farming using broad spectrum antibiotics, I meant that as a bad thing. Its stock standard practice to start with broad spectrum when you don't know the agent, and move to specific antibiotics once the aetiological agent is cultured / isolated etc. Broad spectrum antibiotics can be given as a preventer, but even then in humans there needs to be a clinical reason for it. In other words we don't give it to the wide population. With farming, they seem to give antibiotics as a "growth promoter" to the entire population of farm animals.

I would also like to add on one of Skimmer's points, that antibiotics are being developed to target the mutations in bacteria. Thats pretty neat. At the present time, its possible (in some cases) to overcome the antibiotic resistance to a certain drug by adding a second drug to counteract how the bacteria becomes resistant in the first place.

For example some bacteria produce a beta-lactamase enzyme which breaks down part of the penicillin structure. To overcome that you add Clavalunic acid to the penicillin drug called amoxycillin to form augmentin. The clavalunic acid overcomes the beta-lactamase enzyme, allowing amoxycillin to be effective again. Another example of this tactic is with the drug tazocin, which is a combination of the penicillin, piperacillin + the drug tazobactam.

[K. A. Pital]

We don't just get the super germs from antibiotics, we also get them from the massive use of disinfectants on everything

Resistence from cleaning solutions? Seriously? So people in the First World clean and sterilize rooms using antibiotics? What the bloody fuck of a method is that.

Because outside, you know, people sterilize rooms with UV sterilizators and, uh... clean spirit. Maybe supertoxic acid solutions, too. That's about it.

Germs cannot become resistant to a whole variety of complex antibiotics because they've been repeatedly subjected to UV sterilization or acid or alcohold massacres, really. Unless there's something I don't know about biology. Blaming cleaning for resistence is weird.

[Andrew_Fireborn]

I know my relations buy antibacterial hand soap.

A large number of cleaners advertise as killing 99.9% of germs on surfaces...

How much of a cross-over the chemicals used in these products has with medicinal antibiotics, I have no idea, but they most likely aren't helping matters.

[Serafina]

Antibacterial hand soap does indeed remove "99.9% of all germs".
So does normal, non-antibiotic hand soap. Without actually producing antibiotic-resistant bacteria.
Which is why the majority (or even all, i think) of German hospitals no longer use antibiotic hand soap. It's no more effective than normal soap and doesn't replace the need for a proper disinfectant.

[GrandMasterTerwynn]

Bloody hell that's even more than I assumed.

Of course you are right that the main thing is to use what we have less frivolously. Get rid of factory farming for animals, for example (as if we needed more reasons to get rid of that particular horrorshow). Can't really speak for doctors proscribing stuff unneccesarily, but I have witnessed plenty of people not completing their courses of antibiotics because 'oh now I feel better'.

I'm not sure how much the huge animal market actually matters, lots of focus it put on that issue but the actual range of antibiotics being used for that purpose is limited. Also something to consider is the hospital environments themselves. We don't just get the super germs from antibiotics, we also get them from the massive use of disinfectants on everything. Surgical tools themselves are sterilized by high pressure and high heat processes, but everything else is being scrubbed down with the same couple cleaning compounds over and over and over again... this issue is kind of mind boggling to think about. If we can't use cleaning products WTF will we do, boil specific rooms with steam once a day?

Some of the cleaning compounds used are pretty toxic to life in general. It is extremely difficult for a bacterium to evolve a resistance to having its cell walls oxidized, or its proteins denatured, which are the actions performed by common disinfectants like bleach and alcohols.

It is far easier for them to evolve resistance against substances that bind to specific proteins on the cell walls, or interfere with specific metabolic pathways. But bleach and alcohol-based disinfectants are so comprehensively lethal to microbes that they won't evolve a resistance to them. Though steam, ozone, and UV-based disinfection techniques will be effective as well without adding to microbe resistance.