Existing Drugs Fight Antibiotic-Resistant Bugs 110
sciencehabit writes "Medical experts have been powerless to stop the rise of antibiotic-resistant bacteria and are increasingly desperate to develop novel drugs. But a new study finds that smarter use of current antibiotics could offer a solution. Researchers were able to keep resistant bacteria from thriving by alternating antibiotics to specifically exploit the vulnerabilities that come along with resistance—a strategy that could extend the lifespan of existing drugs to continue fighting even the most persistent pathogens."
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Ahh, sulphas and 'cillin's, the drugs so many people are allergic to. I know childhood 'cillin allergies can go away (medical test is take a dose, and have someone standing by with an epipen and benadryl, I wish I were kidding). But not sulpha drugs; once allergic always allergic. And the allergy transfers to so many non-antibiotic sulphonaminids that is's mind boggling.
The rugby joke didn't go over my head, I just was picturing people who only one of those drugs would work for.
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"It's Bactrim, no it's Zifromax, now Amoxycillin, back to Bactrim... SCORE!!!"
No, the pharma industry will package them in a special containers that deliver one identical looking pill (with different content) each day for only 4 times the price as if we'd rely on the user remembering when to take what.
Perhaps if (Score:4, Interesting)
I was thinking somewhat along the idea, written in summary. We could battle resistance with somekind of phasing of antibiotics in and out of use.. For example we could phase out one type of antibiotic for say decade, then bring it back and phase out another. Could this work?
phaser ... done in days (Score:3)
Re:phaser ... done in days (Score:5, Interesting)
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The selective pressure to gain resistance is a lot stronger than the evolutionary forces to lose it when it's no longer needed, so I'm not sure that'd work on such short timescales.
Re:Perhaps if (Score:5, Interesting)
10 years seems too long to me, actually. The problem is, a patient has an infection that's resistant to 'cillins or 'mycins or 'floaxins or 'sporins or what ever. Instead of throwing the biggest drug available at it (say it's resistant to all 'cillins) then throw something weak from another family (keflex or something on those lines). Don't throw Vanc/Gent at it, or Rocephin. But make sure the infection is dead dead. Not just in hiding and building a resistance to that new antibiotic too, treat with the full regimen and retest afterwards! And for gods sakes, drill it into the patients heads to take all X days worth, don't skip just because 'you feel better'!
Having just gone through this over 3 years, it's easy to say and harder to do. Bacteria hide (UTIs are bad about this, so are cysts), and when they do they can build up resistance and patients want the strong stuff so it kills it fast. But, and this is a bit of pt side talking, I wish I got the weaker meds first so the later infections weren't resistant to everything but Vanc/Gent/Strepto+Linazolid. Having on two drugs types available post-surgery (both 'of last resort' types) was a pain in the ass.
Second thing to do is for hospitals to be a little more cautious. Every antibiotic flavor for two years left my gut bacteria resistant to nearly everything. So, post surgery, and abscess appeared. Guess how many it was resistant to? Linazolid is the first antibiotic I've met that was more expensive, by weight, than gold. And that was the active drug weight, not the horse pill the crammed it in to!
For the curious, psuedomonas a started it and several idiot docs didn't call infectious disease to learn that omnicef and ampicillin wouldn't work; but they made everything else resistant. Then 4 PICC (well, 3 PICC and one PIC that got a little misplaced) for 3rd gen cefs' which are anti-psudo drugs. All the while, entero was getting resistant to all of those (lucky they killed all the e. coli or I'd have been toast).
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Re:Perhaps if (Score:4, Insightful)
> phase out one type of antibiotic for a decade ...
Nice idea in theory, but remember that infection types aren't monolithic. In your region, a given bacterium might have developed a strong resistance to amoxicillin, while in the next city over, they've become resistant to something else. Now add travel to the mix: a guy with methicillin-resistant germs flies across country, then shares his infection with the folks in that region.
NOW add in the fact that these things are most commonly spread in hospitals by overworked staff not washing their hands each and every time they visit a patient's room. One study I read several years ago found that the keyboards on the computers were loaded with MRSA, for example -- which could easily have been controlled with a puff of Lysol and a bottle of hand sanitizer.
At any rate, the article's premise makes sense to me. My doctor told me a few years ago that these things seemed to move in cycles: bacteria would became resistant to one antibiotic, then another ... but it might eventually go full circle. He said he was having a lot of success treating some patients with plain ol' penicillin and doxycycline again.
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The cycle things still works, but will be more efficient if synchronized between all hospitals so that everyone phases out the same antibiotics at the same time.
What you want to do is essentially to on a global decide which medicine is least effective and stop using it until it becomes universally potent again.
Then you switch it out for the new least efficient until you have cycled them through.
Re:Perhaps if (Score:4, Interesting)
New law, if you get an infection from the hospital, your stay is free. Just watch how fast they find the resources to sanitize everything.
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I'm sure the families of the dead who got saddled with huge bills are deeply sympathetic to those who suffer the horrors of hand washing...
If I leave my car with a mechanic and he lets it roll back into a tree, he's on the hook for the repairs. Why not a hospital? If it really so much to ask for the same level of professionalism we expect from auto mechanics? (who, by the way have a much bigger problem with grease, grit, and harsh hand cleaners damaging their skin)
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SMS Text Updates (Score:2)
Hey, we should set up a system that texts our doctors immediately when it is time to shift to different antibiotics, in order to combat the absolute latest resistant bacteria. Unfortunately we'll have to come up with quadrillions of $ of "support" funds to re-educate most of them from relying on Big Pharma for directions on what they should do (i.e. "Just keep giving out full-spectrum XYZocillin, it's grrrrrrrrrrr-eat!")
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Another strategy (Score:5, Insightful)
Don't use them unless they are necessary.
Re:Another strategy (Score:5, Insightful)
Re:Another strategy (Score:5, Informative)
If only "pharma can't be bothered to create new antibiotics" were the issue. As it stands antibiotic development is a very active, very well funded private and public research effort. (As you'd expect from a field where whoever gets there first becomes unspeakably wealthy, there are an awful lot of startups.) It's just not turning up anything.
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Carbapanem is the last I heard about. Finally got a dose of that recently, or it might have been carbenacillin...was post surgery, I had methadone, fentanyl, morphine, and lidocaine drips, my memory has a few holes. But you are right, the stuff being developed now is so strong that they kill human cells as easily as bacteria. It's almost like chemo drugs now.
Still need amikacin and a few of the 'penems to fill my punch card for antibiotics of last resort.
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It's not just an Asia thing (Score:4, Insightful)
Seem quite simple, doesnt it? The fact that cattle, fish and shrimp feed in asia have huge amounts of antibiotics as a "preventive" measure to keep the animal from going sick, and the resistance the bacteria gain dealing in that sick field, and whatever trickles up the food chain doesnt seem to bother anyone, has long money is made. And nobody will care until it is too late. Big pharma also doesnt care, quite by the contrary the patents have long expired, and antibiotics are bought by the shovel, as soon as they stop working they will have then gov "fund" to further develop very expensive nanomeds. This seems like a stupid plot from a bad scifi movie.
This isn't just an Asia thing. You have described at exactly how food production in the USA works. I'm sure that there are other countries where it's the same. Food production in the USA is Big Business and Big Business always gets what it wants. What they want is zero loss and the way to achieve this is to use high amounts of pesticides that kill any bug that dares to get near produce and feed antibiotics to animals to keep them alive long enough to slaughter them.
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What they want is zero loss and the way to achieve this is to use high amounts of pesticides that kill any bug that dares to get near produce and feed antibiotics to animals to keep them alive long enough to slaughter them.
Incorrect. What they want is to increase profits to the maximum amounts, and pesticides and antibiotics ain't cheap.A farmer is looking for the biggest yield for the lowest price, and wasting money on pesticides that aren't needed is not a good way to increase your profits. Farmers want t
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True, but antibiotics have the effect of making the animals gain more weight. The farmer can make more than the cost of the antibiotics back by selling more product, and so has an incentive to use them whether or not the animal is sick.
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That attenuates the problem, but it doesn't stop it. Even those drugs that are limited to critical human medical uses are starting to run into resistance problems, and we're simply not finding new ones. The chemical space has become alarmingly barren.
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Everyone knows Placebin is absolutely the most powerful anti-viral known to man. Give them that.
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Here's something to think about the next time you feel you n
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And if you are one of the many poor slobs whose health insurance is "go to the ER and hope they write off the check because I am in poverty and have no hope of paying it back"?
Recall that several congress critters cited exactly that scenario when they were debating against single payer health reform ("We already have single-payer health care, just go to your local Emergency Room!")
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And if you are one of the many poor slobs whose health insurance is "go to the ER and hope they write off the check because I am in poverty and have no hope of paying it back"?
Most clinics are run by the same hospital systems that house your local ERs, so you get the same write off service there as you do going to an ER. And the ones that aren't are run usually run by companies that just won't see you without insurance or charities and have you pay as you can.
The thing about ERs is they have a much higher liability than clinics, and as such they must treat everything as a life or death situation & do EVERYTHING they can to make sure it isn't before they let you go, or have v
The bacteria are like the Borg. (Score:3)
In TNG, Starfleet made it a regulation to alternate phaser frequences in order to fight the Borg. The Borg soon adapted to that strategy.
It would be strange for the bacteria not to adapt to the strategy of alternating antibiotics as well. It seems the bacteria have a very good pattern recognition mechanism.
Re:The bacteria are like the Borg. (Score:5, Insightful)
Except that bacteria don't adapt to a "strategy". They adapt to the conditions at exist at the moment, with no consideration of the future implications of that adaptation. Because, you know, bacteria aren't intelligent.
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bacteria aren't intelligent.
That's what they want you to think.
Re:The bacteria are like the Borg. (Score:4, Funny)
Because, you know, bacteria aren't intelligent.
Have you considered that maybe it's you who just doesn't go to the kind of places the smart bacteria frequent?
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Except that bacteria don't adapt at all (lacking freedom of will to do so and all). They experience random mutations that cause some of them to be better adapted to circumstances than others. If in hindsight some of those mutations happen to be really smart choices considering (then) future events, those bacteria will emerge as dominant because the other ones will have died.
Because, you know, that's how natural selection works
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Re:The bacteria are like the Borg. (Score:5, Interesting)
Actually it is a bit messier than that: http://en.wikipedia.org/wiki/Horizontal_gene_transfer [wikipedia.org]
So the genes for antibiotic resistance don't even have to be evolved by the same organism, nor must they remain there, they can spread separately from the pathogen. The germs you fight may not even be the main resevoir for those genes.
I actually wonder how long it will be before someone engineers a slutty bacterium that is very successful at gene transfer with its own kind and load it up with genes for antibiotic vulnerability. Hell it wouldn't even need to be a traditional antibiotic.... anything you can program it to recognize and trigger cell death should do the trick.
It would be kind of like air dropping syphlitic hookers on the enemy.
Re:The bacteria are like the Borg. (Score:5, Informative)
Fortunately, it's even messier than that: https://en.wikipedia.org/wiki/SOS_response [wikipedia.org]
This is the phenomenon the researchers are exploiting. Not every antibiotic resistance comes from a neatly-packed, horizontally-transferable gene; often, the bacterium is instead evolving alternatives to perform common tasks like the binding of ribosome cofactors. The most transferable antibiotic resistance genes are often enzymes that degrades the antibiotic. These can be overwhelmed; just hit the bacteria with several drugs at the same time. HGT of new-and-improved constitutive genes certainly still happens, but it's much less common, and may not be compatible across species. (As an extreme example, we only recently started finding cases where the ribosomal 16S gene was transferred, and both instances were within the same genus.)
So... there are definitely some strains, like MRSA [wikipedia.org], that have evolved to be ruthless killing machines, and these are particularly dangerous because their DNA can be taken up by other bacteria, but at present they represent a small percentage of all potential hospital-borne pathogens. They kill a lot (MRSA is believed to be the fourth largest cause of death in the US and kills over a hundred thousand people a year), but because the resistance comes from all of these key constitutive genes that have co-evolved, they mostly stay put. This is why a lot of research now focuses on preventing biofilm formation.
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Because, you know, bacteria aren't intelligent.
Yet.
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A perfectly valid analogy, in my objective opinion.
Shifting drugs, phages, other strategies... (Score:2)
The biggest thing to make this work is that we need faster and cheaper detection of specific attributes of any bacterial infection. DNA typing is all well and good, but we still need to work on being able to attribute specific characteristics to a given strain. Something that takes less than an hour and $20 would be great.
I remember first proposing this back when I learned about phages - viruses that target bacteria. Thing is, they're much more specific to any given strain of bacteria than antibiotics ar
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But when you have hours or minutes (or even a day, just long enough to get a culture and preliminary resistance check) to start treating a bacterial infection before septic shock sets in, DNA typing and creating a phage takes too long. The opposite problem is that if your first guess isn't 100% effective, than you also just upped the chance of training the bacteria to be more resistant.
It's not the standard e.coli UTI that causes resistances (chances are macrodantin or 'cillin or 'sporin will kill it good).
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But when you have hours or minutes (or even a day, just long enough to get a culture and preliminary resistance check) to start treating a bacterial infection before septic shock sets in, DNA typing and creating a phage takes too long.
That's probably one of the best reasons to invest money into biotech research - to develop instruments and processes to squash the whole thing into a matter of hours at most. Compared to space colonization and similar projects, this one doesn't seem all that impossible (not to mention the usefulness and therefore desirability of synthetic organisms for other fields of human endeavor)- who would have thought in, say, the 1970's that whole-genome sequencing would a mundane affair one day? And it is now.
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It would be nice, but designing a phage doesn't seem like a process that could be sped up that much
I think that in time, this will only be a software problem.
But making the phage and making it only kill what you want it to kill, there is your DNA scan for each different sample you make, and then for each sample of a good one that you get to make sure it didn't mutate in a bad way
I thought that this is how microbiological samples are studied today? At least I'm aware of virologists doing exactly this. You simply scan everything you have in the sample, and the computer sorts out the results into strains of whatever you happened to have there, including things you've never seen before. This is a nut for bioinformaticians to crack, not for medical equipment makers or for M.D.s.
a phage that doesn't die when it's target does
Phages can't "die" because they don't live, at leas
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But making the phage and making it only kill what you want it to kill, there is your DNA scan for each different sample you make, and then for each sample of a good one that you get to make sure it didn't mutate in a bad way . . .
One of the problems with phages is that they DO tend to be extremely specific, and it's not like a phage that targets bacteria is going to mutate to attack humans. Maybe your gut fauna, but even that's unlikely.
But then we run the risk of phage resistant bacteria, or a phage that doesn't die when it's target does; though if that meant enhanced immunity to a target bacteria for life, sign me up right away!
That's part of the fun, the phage mutates to keep up with the bacteria. It's like you're giving the infection the flu just before it's title fight with your immune system. ;)
As for the phage, once the target bacteria is gone it'll probably be eliminated from the body pretty quickly - it can't repli
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But when you have hours or minutes (or even a day, just long enough to get a culture and preliminary resistance check) to start treating a bacterial infection before septic shock sets in, DNA typing and creating a phage takes too long. The opposite problem is that if your first guess isn't 100% effective, than you also just upped the chance of training the bacteria to be more resistant.
That's why I said the #1 obstacle to this is speed of testing. You need a fast way, preferably under an hour, to test the infection and determine the best 'mix' of preventatives - hitting an infection with phages and antibiotics on top of the body's immune response should be an easy knockout on most infections, especially if you're specifically selecting for maximum vulnerability.
Would phages work in vivo? (Immunity) (Score:3)
Using viruses as weapons against bacteria seems like an awesome idea, however, wouldn't a person's own immune system start attacking its ally the phage?
I mean, parts of the immune system, all they do is react to antigens, and phages would be seen as just another invader that doesn't belong, regardless of the fact that it is attacking a common enemy.
For this reason I'm not sure phage therapy would necessarily work.
--PM
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It's my understanding that the Russians had some success with real world trials. Your body's immune system attacking the phage as well is indeed a concern, but so isn't it attacking the antibiotics.
The trick is that the virus is released after the bacteria, and while the body will eventually respond to it it should take enough time to take a good chunk out of the infection.
Designing them so the human body doesn't quickly generate an immune response against the phages would be a good trick though.
There, fixed that for ya (Score:4, Insightful)
"*Big Pharma Companies* have been powerless to stop the rise of antibiotic-resistant bacteria and are increasingly desperate to develop novel drugs."
Here's a hint: Stop indiscriminately throwing antibiotics at everything that moves. It's precisely the over-use of these drugs that has created the problem in the first place.
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Here's a hint: Stop indiscriminately throwing antibiotics at everything that moves. It's precisely the over-use of these drugs that has created the problem in the first place.
Why would pharmaceutical companies want to do that? As maximising profit presumably requires them to maximise sales of their products, and hence maximise usage.
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Outsmarted by bacteria (Score:2)
It must be funny to make a new product that kills a living being and then see how in a matter of years the being evolves to be immune to your product or to bypass it in some novel way.
It must be great to understand that your amazing attacks are avoided by a system that requires no intelligence. That you're being outsmarted by the natural algorithm of evolution.
Copper cladded work surfaces and fittings (Score:5, Interesting)
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I've posted in this thread so can't mod you up now but very interesting! I knew silver had antibiotic properties but not copper. Only problem with copper is oxidation, requiring maintenance, which is possibly why they switched.
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That paper looks very interesting, and since some of my pediatric doctors are now heads at UVA (another university hospital) something that might be of use to them. Though, there had to be some reason they got rid of silver and copper equipment anyways? I dunno, maybe the gurnies and such get autoclaved, which copper might not do so well with.
I see a bigger problem with shared rooms, frankly. One PT with one resistance infection sharing a bathroom with another, and those bloody grippy hospital socks getting
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No need for that, just polish it thoroughly every so often. Worst case use a buffing compound to remove a tiny bit of the surface material.
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Yes. This is why household plumbing is largely copper. PVC is a little cheaper and easier to work with, but it doesn't have antibacterial properties so it should only be used on water lines where necessary.
Apparently, plumbers are smarter than hospital administrators when it comes to bacteria.
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No, that is not why copper is used by plumbers.
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Probably not. Alloys tend to have different surface reactivity to their component parts. (Which is why you alloy iron to make stainless steel, of course...) Be interesting to try though.
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The Navy has known the answer to that for centuries. Make the doctors and nurses that got caught not washing their hands polish it.
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Antibiotics are necessarily weaker: they can't kill YOU. You'd have a point if we started seeing bu
Asia is out of control (Score:5, Interesting)
Over prescription of antibiotics is a huge problem here in Asia mostly due to cultural face saving practices. In the West when you go see a doctor you are sometimes, probably not often enough, told to just go home, stay hydrated, rest and that you don't need any medication because there's no medication that can really help.
In Asia however, when someone sees a doctor they expect to go home with something. Even though the doctor's advice is 'respected' it would be a loss of face for a patient seeking treatment to be told to just to go home and rest, no medication is needed. It's hard for Westerners to understand, and IMHO serves very little purpose in today's society, but Asians would view coming home from a doctor without medication as the doctor not doing their job. Also, by not providing some kind of medication the doctor is basically, in the Asian mind, telling the patient "you are wrong, there's nothing wrong with you" which would be a big loss of face for the patient.
There's also a cultural service and purchasing custom that applies but it's much more esoteric and difficult to describe. Briefly, there's an expression "buy 10 buns, get 11 bags" because everyone is conditioned that a transaction is not complete until the goods or services are delivered well and completely packaged. It's a nice polite custom and all but you should see the dumbfounded look on many vendors' faces when I tell them I do not want a plastic bag for my purchase(s). It may sound irrelevant but it comes into play at the doctor's office in terms of, the service transaction is not complete until medicine is delivered.
So, doctors here are not able to go against the cultural grain, even though they know medically and scientifically that antibiotics will do more harm (in the long run) than good, the cultural conditioning is too strong so they always prescribe and 9 times out of 10 it's antibiotics. I was a paramedic in the US for years and I know treatments are highly relative to cultures. I've got no problem with cupping or coining or other 'treatments' that appear to be absurd when viewed through the filter of my culture but, none of those practices have an international impact.
Over prescription of antibiotics is a very significant international problem and Asia is doing the world a huge disservice by allowing it's cultural customs to influence medicine to such a degree in this matter.
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Placebos?
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Already-useless antibiotics are an excellent placebo in that situation, side effects notwithstanding.
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It says he sends her antibiotics, not a prescription, no?
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Wow, I would have thought they'd have stopped that by now. When I was stationed in Thailand in 1974, the only drugs that had any kind of control were LSD, heroin, cocaine, and marijuana*; they were outlawed (US treaty). Any other drug you could get over the counter, including antibiotics, quaaludes, amphetamines, you name it.
*Heroin and marijuana was freely available in the street and incredibly powerful. E.g. in the US and Europe, heroin is 1-2% pure, in Thailand it was 98% pure. Rather than shooting it up
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That happens in the US too, particularly from the wealthy (if you don't have the money to pay for 'em, you won't be fishing for meds -- at least not antibiotics!) I used to know someone who would call their doctor every time they got a cold, and the doctor would phone in a prescription for Azithromicyn [sp?] to the pharmacy without ever even seeing them...
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OK, but that does not really seem to be the main issue here. If the doctors needed to proscribe anything, they could proscribe some vitamin C or whatever.
Doctors have dozens of alternative general medications that would do less damage than prescribing antibiotics.
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Indeed, they should!
I should have mentioned in the OP that education on issues like this is severely lacking here. So, from the patient's POV, I think there's an expectation of antibiotics for 2 reasons. Today people are used to getting them for everything and there was a time when they were thought of as a cure all / wonder drug of sorts and that thinking persists. I know far more about the challenges doctors face around this issue than I do about patients' expectations. However, I'm confident a controlled
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At any rate, the larger contributor appears to be the agricultural industry.
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Aside: face [wikipedia.org] is actually a very translatable concept that most educated Westerners understand easily; it mostly seems to be cultural anthropologists who are convinced that it's hard to understand the consequences of being embarrassed in front of important people to one's social status. (Maybe they don't remember giving their thesis defences?)
Joce640k really hit the nail on the head. Not only does this problem exist in the English-speaking world as well, we developed a whole class of drugs just to deal with d
Sorry, my mistake (Score:1)
I thought they figured out long ago that multiple antibiotics simultaneously, especially ones with different mechanisms (such that two, not one, mutation would be required, and thus infinitely less likely to happen) was the way to go, and the only thing slowing them was stacking side effects.
If not, sorry, my bad. I should have published something in the mid 1990s when this first occured to me. Sorry dead people :(
This research is interesting because it makes headway where one mutation increases sensitivi
Ah, penicillin (Score:1)
The only drug that actually works. And I don't mean it's derivatives. Unless you are allergic to it, it's still the best drug on the market. If I have a bad cold I can shed it within 8 hours or so as opposed to something like amoxycillin which takes days at best. But since it's dirt cheap the drug companies are pushing "modern" drugs at a premium and telling you they are better.
A couple of thoughts (Score:2)
Perhaps drug researchers can find a way to allow the original organism in some antibiotic sources, say penicillin mold, to react to the evolved bacterium, thus changing its antibacterial toxin naturally as it must have done for millions of years to keep ahead of whatever was trying to consume it. Could we let nature battle the evolving immunity issue naturally? Large tanks of naturally acquired, say penicillin mold again, with its natural genetic variations placed in close proximity to the antibiotic-resist