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Potential Cure For Antibiotic Resistant Infections
kpw10 writes to let us know about research to be published this week that offers hope in the battle against multi-drug-resistant bacteria. "Researchers at the University of North Carolina at Chapel Hill have discovered that two drugs used to treat bone loss in old folks can both kill and short-circuit the 'sex life' of antibiotic-resistant bacteria blamed for nearly 100,000 hospital deaths across the country each year."
what happens when the bugs become resistant to these two drugs as well?
The higher the technology, the sharper that two-edged sword.
It's always good to see existing drugs being used in new ways, because it shortens the amount of time it takes to get the treatment to market.
Um, doesn't marriage do the same thing?
Just asking, because it would certainly save a lot of money if we just get these bacteria to marry.
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So, the few bugs that escape this new form of microbial torture will simply become stronger and even more resistant. Great. I am not a biologist, but are there any other ways of getting around this war of escalation?
Maybe scientists could find some other critter that the bugs like better, like cockroaches or the small dogs that live in women's purses.
I'm a skeptic about a lot of things in medicine (I live in that world), especially "wonder drugs", and the writer of TFA demonstrates his limited skills in microbiology enough to make me cringe. But the science here is going to be fun to see.
Don't get me wrong - we need to know the doses, the regimen, the side effects at antimicrobial dosing, and all the rest of the nuts-and-bolts pharmacology. On the other hand, the putative mechanism, which is to interfere with sharing of genes between bacteria, is in itself ground-breaking. Used properly (that is, not overused and used with care), this could prevent rapid resistance emergence in bacteria where the treatment itself takes weeks to months (osteomyelitis, for example, or infection with certain stubborn bugs). These drugs (etidronate and pamidronate) have their own not-insignificant side effect profile, of course, and there are no guarantees at this stage.
I'll be interested in the actual research, because TFA is filtered through a layer of ignorance and sensationalism, but it sounds interesting.
... except for that fraction of a percent that's immune to the drug and can breed anyway, and then we start all over again.
William of Ockham had no beard. The most likely explanation is that it was chewed off by squirrels every morning.
You didn't read the whole article. The drugs were initially tested for the property of blocking the transfer of genes for multiple drug resistance. But they were surprised to find that it specifically killed those bacteria which had already received the upgrade package. Multiple drug resistance is evidently a specific trick - not multiple resistances to multiple drugs, but a single resistance mechanism that blocks nearly all drugs, and that can be passed from one species of bacteria to others. These newly-tested but available drugs kill any bacteria which have adopted that mechanism.
"with their freedom lost all virtue lose" - Milton
...also a proven way to virtually extinguish one's sex life.
just put them in an autoclave.
The microbes, or the patients?
The higher the technology, the sharper that two-edged sword.
Always a concern, but the trend in medicine over the past decade or so has been to reduce the number of times we prescribe, even as we increase both the dose and duration of care when we do pull the trigger. Antibiotic resistance has been strongly linked to inadequate dosing (killing only the susceptible bugs, while letting the borderline-resistant clones reinforce themselves), as well as to courses too short or patient noncompliance.
Patients are part of the problem too, since there is a tendency (cultural in some cases, personal in others) to demand that a doctor "do something" to fix the problem. Antibiotics were perceived for a long time as something harmless to give in those circumstances, but that perception is fading fast. If anything, the trend now is to err on the side of letting things play out a little more to see if antibiotic therapy is really needed.
This has also caused physicians to have to explain the situation better. I know for myself that when I am explaining to a suspicious parent the reason that I'm not going to give their child an antibiotic for their viral infection, I don't waste a lot of time explaining resistance. If they already understand resistance, they're not asking for antibiotics. If they don't, it just sounds like I'm making things up. I focus instead on side effects and cost, and my typical (true) statement is "about all I can do with antibiotics would be to give your child diarrhea to go with her cold." This is surprisingly effective, especially in the parents of non-potty-trained toddlers.
None of which stops me from pulling out the stops when I'm faced with a septic kid or a real infection that needs to be nuked. In those cases, though, I'm very careful to make sure that the regimen I use is appropriate, considering the resistance patterns and the risk of making them worse.
Now if we could only get the idiots who lace animal feed with antibiotics to do the same. Ever wonder where resistant strains start? Hint: it ain't just in the hospitals.
I hate to have to tell you this, but fewer people get sick and die from the "superbugs" than died from their predecessors. Despite what you were taught or at least led to believe, as a general rule, antibiotic resistant bacteria are not "stronger" than the non-antibiotic resistant versions. That is why you very rarely hear of someone getting infected with antibiotic resistant bacteria outside of a hospital. Antibiotic resistant bacteria are at a significant competitive disadvantage when no antibiotics are present. Many people are not aware disease causing bacteria spend most of their existence not causing illness (for various reasons), in these settings the non antibiotic resistant bacteria generally completely overrun the antibiotic resistant bacteria.
The truth is that all men having power ought to be mistrusted. James Madison
Just a nitpick, but anti-biotics don't really help fight against viruses.
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Now I'm not a doctor, but it seems to me that (as is usually the case) it's not that simple. Among the things that come to mind:
1. Drug resistant bacteria aren't as much caused by taking too many antibiotics, but by taking too little of an antibiotic. People take the antibiotic for 2-3 days, then they feel better, and figure out "why bother taking the rest?" Or they take an antibiotic, it makes them feel worse, skip the rest of the treatment because they know better than the doctor. Etc.
Problem is, they have a shitload of bacteria left at that point.
Will someone decide to skip their bone loss drugs too? Probably, but I'd assume somewhat fewer.
2. The fact that it's already widely used to treat bone loss, should probably tell us that if it was that easy to develop resistance to it, it would have happened already. Not saying it's impossible to, but it might just take a lot more time.
3. The relatively fast development of resistance is massively aided by the fact that bacteria can exchange genes. (Hence the jab about inhibiting their sex life.) So basically once one develops resistance, it can pass that around.
Something that attacks that very mechanism, might slow down the rate of developing and spreading resistance a lot.
A polar bear is a cartesian bear after a coordinate transform.
It's easy to be a sceptic and ask about 'and what about when the bugs become resistant to this'. As a person who had his life ruined by MRSA, I know too well the impact these types of infection have on individuals and families. Anything that can extend the reach of antibiotics (particularly the less toxic ones - I was only 2 or 3 days off being killed by the antibiotic that beat my infection) and decrease the chance of resistance is a good thing.
Hopefully this won't be used promiscuously, and I hope they'll work out the interactions with other treatments, as quite often treatment is multi-modal.
I wouldn't wish what I go through due to MRSA on anyone (except my stepfather, but that's another story altogether.
Most (if not all) antibiotic resistant strains of bacteria accomplish this resistance by disabling the protein which the antibiotic attacks. The reason they had said protein in the first place was because it offered a significant competitive advantage. To be precise, the protein in question in most cases has to do with carrying chemicals across the cell membrane. The bacteria are significantly less efficient at transferring chemicals across the cell membrane without the protein that they have deactivated to be resistant to antibiotics. It is sort of like if you avoid being exposed to poison by not opening your mouth, the poison wouldn't get in, but it would be harder to eat.
The truth is that all men having power ought to be mistrusted. James Madison
100K deaths per year, thats more than an order of magnitude than the number of deaths attributed to terrorism in the last decade. Why are they telling us terrorists are dangerous? Imagine the lives saved if we poured half a trillion dollars to combat this, plus no armed forces casualties and no need to tap our phones or sniff our internet traffic.
There is no right to feel safe thru security vaudeville at the expense of everyone's freedom, privacy and tax money.
Yes, why would there be a lot of deaths in the place all the really sick people go to? Anything so obvious must be an evil plot.
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Yep. I've got patients who do the same (I live in an area where we have a lot of Hispanic immigrants, legal and otherwise). Nothing I can do about it except to talk with them, which I do. I try to encourage them to be reasonable and to take an entire course when they start one (nothing's worse than an occasional antibiotic pill). I have mixed success, but I don't expect perfection and I think my attitude helps the situation. I do get a lot of "do you suggest I start this" kinds of calls and questions and I treat those calls as victories.
This gets me into the whole doctor-as-gatekeeper-for-pills thing that drives me nuts. I challenge colleagues once in a while: in an environment where all medications were available at retail, could they still justify their fees? Could they market themselves well enough to avoid starvation? I think I could, because of the kind of medicine I practice (and because I can sometimes go a dozen patients between giving a prescription), but it's definitely something honest physicians should be asking themselves.
In the no-Rx-required environment, though, there's no question that resistance emerges rapidly. Fortunately, the antibiotics available in Mexico are a small subset of the ones we use here, and most of the ones that patients can buy OTC have broad therapeutic indices (overdose doesn't hurt you much) and are from antibiotic classes (penicillins, macrolides) where we have later-generation alternatives that avoid the common resistances. It's a fluid situation, though, and one that has infectious disease specialists always a little on edge.
More-or-less. There are certainly variations, but there might be critical points in the process that are the same across all bacteria. If a drug targets those, we win. Evolution could help bacteria survive, but there wouldn't be any evolutionary pressure to change this aspect of bacterial reproduction outside exposure to the antibiotic.
An analogy might be something like VX nerve gas and human evolution. We might some day evolve so that VX nerve gas won't affect our nervous systems, but it won't be through exposure to VX, since we basically die instantly if we're exposed. On the other hand, it seems unlikely that we would evolve that way.
After all, I am strangely colored.
...but until you've had an opportunity to get up close and personal with CA-MRSA, you DO NOT know how much fun you are missing.
Starts out like an ingrown hair or pimple. Might even be a spider bite. Then it gets angry. Take a large marble...light it on fire and have it surgically planted underneath, say, two layers of skin. Day three and the redness is now inches in diameter and the bump is still growing and...damn! It hurts! Burns like hell! Pimple my ass! Get that thing out of there! You can't sleep from the pain and you find yourself wondering which would be the better method to dig it out: kitchen cutlery or claw-hammer. In any case, if you don't have a doctor lance it, you're going to have to do it yourself.
Day four and it is open, draining and talk about cheese!! The stuff draining from the now open wound is so toxic, it blisters the surrounding skin. Makes it a bit difficult to remember to trash your clothes, bedsheets, etc., but at least the burning has lessened...a bit.
Ten or twelve days later, after finally getting on an anti-biotic (tetracycline?) that can put up a fight, the fluid draining out is almost stopped, the redness is almost gone and a bit of scar tissue is starting to form. Good news is, now that you know the routine, you can put up a slightly better fight next time - and there will be a next time...unless you died from this incident, of course. You did wash your hands before you helped your kids get dressed this morning, right...?
As a doctor, I want links to studies, good studies, not just anecdotal evidence.
Actually, it would be unwise to prescribe these drugs recklessly for another reason- the bisphosphonates, the class of compounds which these two drugs belong to, can have a rather serious side effect when taken in high doses for long periods. Bisphosphonates taken in high doses for long periods can cause osteonecrosis of the jaw, though it should be noted that etidronate and clodronate are older drugs with far less potency than newer drugs in the class like alendronate and zoledronic acid.
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
It is fact that some avoidable deaths are caused by healthcare practitioners, though efforts are made to minimize this. Unfortunately, the US does pretty poorly in this regard, in comparison to other nations with "1st world" healthcare systems.
I don't agree with the OP that doctors are to be avoided -- but I do believe that patients should educate themselves and question the actions of their doctors, particularly wrt prescriptions. There's a reason pharmacists, and not doctors, are the most trusted professionals in the US.
"Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
Before even penicillin, there were the miraculous sulfa drugs, which block a bacteria's ability to make folic acid: bacteria learned to uptake folate just as we do.
Beta-lactams like penicillin prevent bacteria from making peptidoglycan, the material of their cell walls: bacteria came up with beta-lactamase to break it down.
Better beta-lactams like oxacillin and methicillin were developed to be more effective at killing bacteria before lactamase neutralized them: mutant forms of proteins involved in making peptidoglycan (and were resistant to binding lactam drugs) began to proliferate, and now we of course have Methicillin Resistant Staphylococcus Aureus to deal with. (And studies have shown that MRSA bacteremia is just as deadly as regular SA, even correcting for the fact that MRSA tends to hit hospital patients. The rise in community-associated MRSA suggests it can fend for itself in the wild as well.)
Quinolones attack bacterial topoisomerases, the enzymes they use to wind and unwind DNA: mutant topoisomerases beat these.
Macrolides (most of the -mycin family) and oxazolidones bind to bacterial ribosomes to stop protein translation: modified ribosomal subunits beat these.
Vancomycin prevents peptidoglycan formation in by preventing incorporation of the monomers that make it up: modified monomers, and now we see VRSA.
We keep finding new targets for antibiotics, but as the Red Queen said, "It takes all the running you can do, to keep in the same place."
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
Hang on there! This logic of combinations of drugs and such has been tried for a long time. The results always rapidly decline in value. Even if this combination works for now, it will fail in a short period of time.
There is a better way! the USA Laser guys have a tool that could best be described as the Atom Bomb of medicine. It is a very simple system that exposes a person to an intense short duration flash from an IR laser. This device does several wonderful things. The first is that it essentially sterilizes the exposed zone of the person from most bacteria and virus agents. This is really profound and very nearly instantaneous. The next effect is by photoelectric effect it takes the cells of the person in the area exposed and drives them up to full operational energy essentially stopping any tissue destruction cascades.
This process causes nearly instant reduction of edema in exposed tissue. Yes our soldiers exposed to traumatic brain injury could be healed this way because the laser is intense enough to shine right through a person's head. This system also supports rapid tissue healing at rates in the order of 10 times normal. Tissue differentiation to the correct tissue type rather than scar or adhesion types is also greatly improved.
Antibiotics are well named. They are anti-life. This problem with using them in treatment means that their use is a trade off between the death they cause in a patient vs the death they cause in the infectious agent. Wouldn't something better be a good idea?
Never Politically Correct ~ I prefer the facts If you don't like what I say, get a life, or comment yourself.
I haven't read the article because for some reason our corporate firewall doesn't like it (but it's cool with slashdot: ??!?)
Anyway, I know there are multiple paths for drug resistance.
Generally speaking, antibiotics target a specific enzyme or pathway. Take penicillin: it inhibits an enzyme used in linking sugars used in building the cell wall. To evade this, some bacteria make beta-lactamases, enzymes that specifically attack and break down penicillin, while other bacteria just massively overproduce the enzyme that the penicillin targets, so that even under high penicillin dosages, there is enough enzyme activity left that the bacterium can build strong cell walls. Those are completely different forms of resistance, and one drug is unlikely to manage to stop both (unless it just kills the cell, which will of course stop both mechanisms, but that's not what we're talking about.)
If you're interested, here's an interesting article that discussses a bunch of issues related to developing antibiotic-resistance, including quick takes on how it's not really related to massive widespread antibiotic use, to length of time using the antibiotic, and some other widely-held misunderstandings.
Nostalgia's not what it used to be.
Bacteria can take up "free" DNA that's somewhere in the environment (possibly a residue of a dead bacteria). So basically the resistant bacteria does not need to be alive to pass on the resistance genes. http://en.wikipedia.org/wiki/Transformation_(genet ics)