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| October 6, 2007
| Tim
Well, this was interesting last week, so I think we'll open up another one and see what (if anything) develops. My girlfriend & I are going hiking today (going to see the pretty trees turning colors, we hope) so I wish you all a Happy Saturday!
Enjoy! It's a beautiful day out!
Well, here's a topic I've been interested in for a while. Hope it's not too wordy.
The costs of antibiotic resistant infections are difficult to calculate. Those who abuse antibiotics often bear only a fraction of the negative effects, and whether new antibiotics can be produced fast enough to replace the old ones, high mortality due to antibiotic resistance seems a present and future reality.
Farmers regularly give their animals antibiotics which have been approved for human use in order to speed up their growth. If we wanted to efficiently produce and distribute antibiotic resistant bacteria, modern factory farming methods come pretty close to what we might design. Biotechnologists, likewise add antibiotic resistance genes to bacteria so that they can determine which bacteria have successfully taken in the marker genes. This is one step in the process of genetic modification of plants. Classes of antibiotics approved for human use are used in this process, probably because the antibiotics and related resistance genes are already well understood. The result is that most plants with specific genetic material added (GM) will also carry genes for resistance to clinically used antibiotics.
Whether the creation and distribution of large numbers of such plants with the genes for antibiotic resistance poses any kind of problem is difficult to determine. link
When I went to China, antibiotics were unregulated and doses too small to cure disease, but large enough to encourage resistance, were frequently recommended. Likewise, antibiotics were frequently recommended uselessly for viral infections (some antibiotics, such as those in the tetracycline
class, can reduce inflammation and appear to be having an effect in viral infections). No proscriptions were needed. Food products (of all things) are increasingly being imported from China where antibiotic resistance is rampant.
MRSA (Methicillin-Resistant Staphylococcus aureus) is becoming more prevalent in healthcare settings. According to CDC data, the proportion of infections that are antimicrobial resistant has been growing.
In 1974, MRSA infections accounted for two percent of the total number of staph infections; in 1995 it was 22%; in 2004 it was some 63%.
link
It is difficult to determine the exact number of people killed by antibiotic resistant infections, since such deaths post-surgery are often
listed as due to "complications of surgery". But some research suggests that mortality is currently significant.
Results Patients with MRSA (Methicillin-Resistant Staphylococcus aureus) bacteremia had more acute renal failure and hemodynamic instability than patients with MSSA (Methicillin-succeptible Staphylococcus aureus) bacteremia. They had a longer intensive care unit stay and ventilator
dependency. Patients with MRSA bacteremia had a higher 30-day mortality rate (53.2% vs 18.4%) and in-hospital mortality rate (63.8% vs 23.7%)
(P
link
An interesting partial solution to this problem would involve using certain types of viruses which attack bactieria, called bacteriophage.
Bacteriophage and bacteriophage therapy has been known about for a century, however the rise of broad spectrum antibiotics, along with a few
poorly conducted experiments early on, prevented their use in the west. The Soviet Union had a facility in Soviet Georgia (George Eliava Institute) since the beginning of the 20th century which produced phage for the Soviet millitary. With the breakup of the Soviet Union, the institution floundered, though it is currently working to find new markets and develop new treatments.
At this point, bacteriophage have strong potential for treating topical and gastro-intestinal infections as well as cleaning food, operating rooms, and certain crops. They also have potential for helping reduce traveler's diarrhea. (Part of being used to the local water has been speculated to involve having the right phages living in your gut.) Attempts by companies like Intralytics to develop long-cycling injectable phage seemed to have failed for the time being.
While it would require a large cocktail of different phages to even begin to replicate the broad-spectrum nature of antibiotics ( Eliava has used such cocktails), the two could be used simultaneously with no bad interaction. And because phage doesn't have many of the problems associated with antibiotics, (resistance, destroying helpful bacteria, significant toxicity) they wouldn't have to require a proscription. While bacteria can become immune to one type of phage, it's far easier to develop new phage than it is to develop new classes of antibiotics. Phage are literally everywhere, and phage 'development' is often just a matter of finding the right spoonful of sewage, then removing those viruses and bacteria which could be harmful.
The USDA has done some significant research on Phages and their commercial application and seems generally receptive to their use, however it's impossible to patent most phage since they're naturally occurring and commercial adoption seems slow going.
Similarly, since phage are usually naturally occurring most cannot be patented. Intralytix's injectable phage would have been an exception, but the company seems to have languished while more traditional uses go mostly undeveloped.
Wow, interesting. I haven't seen anything on bacteriophage treatment at all. I rather like the idea since jumping from bacteria to humans would be rather improbable. We'd still have the problem of resistance, and the possibility of cross bacteria transfers (such as elminating our intestinal flora.)
Do you have more articles on this? I'm curious now...
The Eliava institute and the USDA are good starting points. The silence on this area of research is near deafening, all things considered. Eliava was looking at opening clinics in Mexico or Costa Rica. I don't know what became of those. There's some limited work being done in Poland. And there seem to be some folks in China doing work or treatment with phage, though they didn't consider themselves free to talk to me about it, for a variety of possible reasons. The wikipedia article on the topic is pretty good for general background.
One of the things about phage is that they tend to be very specific. So you can have a phage that will take out a pathogenic strain of E. Coli while leaving a benign strain alone. The good side of this is that you have much fewer of the side effects that you mention, like losing all your gut flora (though you can still theoretically run the risk of shock due to a massive, sudden bacterial die-off, the same as you would with antibiotics.)
I've seen some (unconfirmed) suggestions that
The bad side is that... well, phage are very specific. You need to either know exactly what you're shooting for, which is labor intensive and time consuming, or else use a few hundred different phage at once for a sort of 'buckshot effect.' And even then, it's a lot easier to miss your target when you're using phage. The Eliava institute has tried marketing a product called pyophage, a bandage impregnated with numerous different phage, for that effect.
Also, you have to make sure that your phage is exclusively lysogenic. I don't believe that this is terribly difficult, though.
A sampling of relevant articles;
USDA article
We now present data showing that efficient phage therapy of staphylococcal infections is no longer a treatment of last resort (when all antibiotics fail), but allows for significant savings in the costs of healthcare.
link
The mutability of bacteriophages offers a particular advantage in the treatment of bacterial infections not afforded by other antimicrobial therapies. When phage-resistant bacteria emerge, mutation may generate phage capable of exploiting and thus limiting population expansion among these emergent types. However, while mutation potentially generates beneficial variants, it also contributes to a genetic load of deleterious mutations.
link
The bactericidal activity of bacteriophages has been used to treat human infections for years as an alternative or a complement to antibiotic therapy. Nowadays, endolysins (phage-encoded enzymes that break down bacterial peptidoglycan at the terminal stage of the phage reproduction cycle) have been used successfully to control antibiotic-resistant pathogenic bacteria in animal models. Their cell wall binding domains target the enzymes to their substrate, and their corresponding catalytic domains are able to cleave bonds in the peptidoglycan network. Recent research has not only revealed the surprising rich structural catalytic diversity of these murein hydrolases but has also yielded insights into their modular organization, their three-dimensional structures, and their mechanism of recognition of bacterial cell wall. These results allow endolysins to be considered as effective antimicrobials with potentially important applications in medicine and biotechnology.
link
Preclinical testing of the experimental pseudomonas phage preparation on white mice revealed that the therapeutic efficacy of the phage preparation was higher (80-100%) than that of the antibiotic-ciprinol (50-80%). Noteworthy, 100% therapeutic efficacy was observed after combined application of the antibiotic and the phage preparation.
from the Eliava Institute
Isolation and characterization of nine bacteriophages that lyse O149 enterotoxigenic Escherichia coli.
Hope this helps, Michael!
While researching the topic to make sure things were up to date, I came across this interesting discovery. I wonder how long it will take for drugs like this to be used clinically.
US scientists believe they may have found a way to stop the growing problem of bacteria becoming resistant to current drug treatments.
They have found drugs called bisphosphonates block an enzyme used by bacteria to swap genes, and acquire or spread resistance to antibiotic drugs.
They also showed that interfering with the enzyme could destroy drug resistant bacteria cultured in the lab.
Our discoveries may lead to the ability to selectively kill antibiotic-resistant bacteria in patients, and to halt the spread of resistance in clinical settings
Exactly how bisphosphonates destroy each bacterium is still unknown, but the drugs were potent, wiping out any E. coli carrying relaxase.
He stressed the latest study was at a very early stage, and that bisphosphonates had only been shown to have an effect against one type of bacterium - E. coli.
link
pubmed cite - 2007 Jul 24
Thanks Ryan, I'll definately look more into it, it looks fascinating.
However, to give everyone whiplash, in a failed effort to try and find a citation for a response to the Chavez/Nero post (regarding people in the audience of Neros plays faking their own death so they could leave), I ran across this fascinating little book:
http://ccat.sas.upenn.edu/bmcr/1995/95.03.02.html
It's something I'll have to pick up at some point, because the narrative is getting to be increasingly familiar. Look at the scripted interactions that go on in regards to political correctness, and the general leaking between reality and fiction in the political sphere. (Is it even really appropriate to call it leaking anymore, as opposed to flowing?)
Wow, interesting. I haven't seen anything on bacteriophage treatment at all.
Our oh-so-shallow media certainly fails to cover (in any depth) many of the most important subjects I could imagine.
For example, here is an interesting article on how "tin whiskers" are destroying our electronics -- found via EU Referendum, who also seems to debunk the contention that led-based-soldier presents a significant threat to groundwater.
Great topic, Ryan.
Regarding Mike's "whiplash" change in topic, I'm not quite sure what the referenced material is trying to say, other than the obvious: that people who surround powerful rulers (who have artistic ambitions) will fake approval rather than risk being killed for giving a wrong response.
So if that's not the central or core point, feel free to enlighten me: I don't claim to be able to parse the author's vague, academic prose, much less ascertain any clear convictions or statements thereof on his part.
For example, I have no earthly idea what "leakage" is supposed to refer to here.
For example, here is an interesting article on how "tin whiskers" are destroying our electronics -- found via EU Referendum, who also seems to debunk the contention that led-based-soldier presents a significant threat to groundwater.
Oh, from the standpoint of a person who has to deal with solder, this is a pet peeve. Tin-whiskers are a nightmare lurking in the dark, and this idiot RoHS nonsense makes my professional life a pain when I have to do re-work. Lead is not only good at preventing tin whiskers, but it also adds great flowing, melting and joining properties to solder.
Also, the picture in the article is cool, Tim. Thanks for linking it! (Heck, it's been a while since I've even seen a picture of an air variable cap.)
What is even more amusing, is that in one of my hobbies, I'm exposed to lead all the time. (Shooting.) While some people who shoot professionally have heath effects, it's pretty rare, and chelation therapy works pretty well.
I have significantly more lead sitting in my closet than I do in all the antiquated electronics in my house.
Now everybody sing along, loosely to the tune of hair:
Gimme lots of lead
dense, beautiful lead
melting, flowing,
ductile, bluish whitish
Give me solder with mo' lead
No more tin whiskers
Here baby, there mama
Everywhere daddy daddy
Lead, lead, lead, lead, lead, lead, lead
Flow it, show it
Long as we can mine it
My lead
---
For example, I have no earthly idea what "leakage" is supposed to refer to here.
Sorry, I've gotten rather used to the academic prose. As to convictions, don't even bother, it's academic prose after all. ;-)
However, it's a book review, the book might be much more interesting.
You've pretty much got the point about the people acting out a script, my point being how much more so is this becoming prevalent with the thatricalization of politics. At any point the cameras can be turned on you, so people are following scripts even in everyday life now.
The "leakage" is the blurring of the line between fiction and reality in politics. Look at the sheer number of things people are believing and arguing in politics that come from fictional sources.
So, just throwing out the fact that our political sphere is now a large center of theatrics, and it looks like there may have been some type of historical precedent for this in Rome, given what happened once the emporers were in place.
At any point the cameras can be turned on you, so people are following scripts even in everyday life now.
Yeah, I thought he might be saying that. It's not true: there's a huge difference between being a theater with Nero or Saddam (where faking your death might up your odds of survival) and, well, the absurd conditions you're citing here.
People don't hold their views because they think a camera (or other public) might be turned on 'em, IMO. I see a vast difference between Rome and the US today in that regard.
Heck, it's been a while since I've even seen a picture of an air variable cap...
Used to have all sorts of 'em.
So, the soldier their selling in the stores doesn't have any lead in it now? Is that correct?
If so, that sucks!
As to the political aspect, I'll have to come to that later. I agree with you, for the majority of people, but there is a sub-class where I find people are doing that, and it's growing.
So, the soldier their selling in the stores doesn't have any lead in it now? Is that correct?
If so, that sucks!
In Europe that's true, but you can still get leaded solder here. The problem is, to sell in Europe, you have to be RoHS compliant, which means you have to have a work area where lead never even enters. (At the mothership, we have a big yellow soldering mat that says "No Lead".) So, that means, despite the fact that I can use lead based solder on my personal projects, the stuff I work on for work can't have lead in it to be safe, compliant, prevent mix-ups, etc. So it's easier, to prevent mix ups between personal and work, to just not use lead based solder on electronics projects. Also, most of the components you can get now days are tinned with non-lead solder because of the RoHS problem. So you really shouldn't use lead based solder with them either because of the differing melting points and compositions.
All in all, RoHS is just a big pain in everybodys butt with marginal gains to the world at absolute best.
To Ryan W re 07 October 2007 posting:
You have to ensure the phages are lytic (ie burst the bacteria)and not lysogenic.
lytic (ie burst the bacteria)and not lysogenic.
Gah, yes I meant that. Thanks.
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Enjoy! It's a beautiful day out!
Posted by: Michael Zappe on October 6, 2007 01:24 PM