Sciencemadness Discussion Board

Bacterial resistance to antibiotics.

White Yeti - 4-3-2012 at 10:42

Hello everyone,

I started a long term experiment in November of last year to investigate the effect of eugenol (from cloves) on bacterial growth.

I started chewing cloves to relieve gingivitis and I found them to be very effective in mitigating pain.

I didn't stop there, I found the taste of cloves -repulsive to some- quite pleasant. In addition to relieving pain, cloves also deter bacterial growth and are extremely effective against the buildup of plaque. I would also like to mention that cloves did not substitute regular oral hygiene practices, they served as a supplement (rather like gum or mouthwash).

As with all good things in life, there comes a point where all this comes to an end. Bacteria, pesky as they are, always evolve to conform to environmental disturbances.

I was wondering....

If I abruptly switched from cloves, to oregano for example (which does not contain eugenol), would the bacteria be resistant to antibacterial substances in both cloves and oregano? Or would the genes for eugenol resistance slowly drop out of the gene pool, at which point I would be able to use cloves again?

I understand this is a rather strange post, but haven't found any documentation on bacterial evolution as a response to an abrupt switch from one antibacterial substance to another.

Any thoughts?

bahamuth - 4-3-2012 at 11:26

Resistance to antibiotics come from degrading the antibiotics inside/outside the bacteria in most cases. So we can simplify it by saying that the bacteria has procured an entirely new gene, or evolved/mutated a gene that already was present. If the enzyme that is coded for by the newly attained gene/new version is so that it attack the benzene ring in small aromatic molecules it would not help to switch to oregano in this case (lets say carvacrol and thymol from oregano was the antibacterial stuff, and eugenol the one from cloves.) .

Read up on methicillin resistant Staphylococcus aureus, as it has procured a gene/enzyme that degrades the beta-lactam moiety and as such will work on a broad spectrum of antibiotics.
And resistance may be from several genetic components working together, even cooperation between different species of bacteria as in certain biofilms.

My guess is that eugenol works on such a wide variety of microorganismal processes that it may never be developed a complete resistance for it.

But to your question, if the gene goes away.. No, they usually stick around for a long time, but may be negativly evolved to an un-active form of the enzyme (if not selected for), but the gene usually stays in place, ready to be selected for and regain its former or even higher substrate activity by random mutation, aided by the force of selection.

Vogelzang - 8-3-2012 at 15:04

Of possible interest

http://www.naturalhealthnbeauty.com/natural_preservatives.ht...

GreenD - 8-3-2012 at 15:45

I've noticed my kratom coffee mix does not spoil after a few weeks, while coffee by itself will spoil within a few days.

Kratom has anti-bacterial properties! :)

White Yeti - 8-3-2012 at 16:21

@Vogelzang, interesting. I wonder why these oils are not used in the food industry rather than sulfites and other nasty stuff. Due to all the preservatives in dried fruits and what not, I've grown allergic to sulfites and many other preservatives. Than again, you can also become allergic to oils, especially if they're used extensively in the food industry.

AndersHoveland - 8-3-2012 at 23:01

The poor have always been, and still are, breading grounds for disease, especially antibiotic-resistant disease.
I think antibiotics should be DENIED to the poor and prisoners, unless they pay for their full course of antibiotics in advance. All too often they start and then do not finish taking their medications because they cannot afford it.

phlogiston - 9-3-2012 at 06:00

The antibiotics given to humans (poor and wealthy) are completely insignificant compared to the amounts used for our livestock.

[Edited on 9-3-2012 by phlogiston]

GreenD - 9-3-2012 at 06:56

Quote: Originally posted by AndersHoveland  
The poor have always been, and still are, breading grounds for disease, especially antibiotic-resistant disease.
I think antibiotics should be DENIED to the poor and prisoners, unless they pay for their full course of antibiotics in advance. All too often they start and then do not finish taking their medications because they cannot afford it.


wow.

White Yeti - 9-3-2012 at 13:04

Quote: Originally posted by phlogiston  
The antibiotics given to humans (poor and wealthy) are completely insignificant compared to the amounts used for our livestock.


Yep, I can't agree more. Some people are also growing allergic to some antibiotics because of how much is used to treat beef and chickens.

@Anders, I disagree. The breeding ground for antibiotic resistant bacteria is primarily in western hospitals. Hospitals use antibiotic after antibiotic to treat patients with weak immune systems (HIV patients). Opportunistic pathogens infect these unfortunate people who need to use antibiotics to live, and presto, you've got a new strain of superbugs. Only in hospitals do you really get strains of die-hard bacteria.

As an aside, does anyone think there is a substance that bacteria CANNOT evolve a resistance to? Can bacteria metabolize hypochlorite? I hope this question doesn't attract AJKOER :P

Bacteria are pretty impressive when it comes to evolving. Some bacteria have even evolved to survive in environments high in hydrogen peroxide:
http://jb.asm.org/content/185/23/6815.full.pdf

Vogelzang - 10-3-2012 at 13:33

For almost two decades sinus infections have been going around in my area and I've been trying to find OTC treatments for it. I found that salt water sprayed into my nose using a wash bottle helps, peppermint leaves aren't too effective, breathing the vapors from clove oil helps to some extent, menthol, camphor, eucalyptus (Vicks inhalors/Vaporub) help a little bit and a half of a Cipro a day (for one or two days) is very effective, but I need a prescription to get antibiotics and my stash is getting low. I found an old bottle of Dristan that was effective, but I don't think they sell those anymore. Recently, I tried breathing the vapors from an old bottle of Lysol and found that it can cure the sinus infection in a couple days. It contains orthohydroxydiphenyl (aka o-phenylphenol) and xylenols which appear to be the disinfectants. I don't think they sell Lysol with these chemicals in it anymore. Its the most effective thing I've found next to taking oral antibiotics, which I don't like to do since I have to go to the doctor, get a prescription and risk getting an upset stomach and diarrhea as well as having a weakened digestive system for a while after taking antibiotics. On the Lysol bottle there's directions for using it as an external antiseptic.




Lysol-front.jpg - 261kB Lysol-back.jpg - 191kB

[Edited on 10-3-2012 by Vogelzang]

[Edited on 10-3-2012 by Vogelzang]

Vogelzang - 10-3-2012 at 14:07

Quote: Originally posted by White Yeti  
Hello everyone,

I started a long term experiment in November of last year to investigate the effect of eugenol (from cloves) on bacterial growth.

I started chewing cloves to relieve gingivitis and I found them to be very effective in mitigating pain.

I didn't stop there, I found the taste of cloves -repulsive to some- quite pleasant. In addition to relieving pain, cloves also deter bacterial growth and are extremely effective against the buildup of plaque. I would also like to mention that cloves did not substitute regular oral hygiene practices, they served as a supplement (rather like gum or mouthwash).

As with all good things in life, there comes a point where all this comes to an end. Bacteria, pesky as they are, always evolve to conform to environmental disturbances.

I was wondering....

If I abruptly switched from cloves, to oregano for example (which does not contain eugenol), would the bacteria be resistant to antibacterial substances in both cloves and oregano? Or would the genes for eugenol resistance slowly drop out of the gene pool, at which point I would be able to use cloves again?

I understand this is a rather strange post, but haven't found any documentation on bacterial evolution as a response to an abrupt switch from one antibacterial substance to another.

Any thoughts?


Try using fluoride rinse after brushing your teeth. Seeing a dental hygienist a couple times a year helps, too.

White Yeti - 10-3-2012 at 16:08

One interesting home remedy I have for a sore throat is a shot glass of vinegar. It's strange, but it works every time. It can upset your stomach though...

entropy51 - 10-3-2012 at 18:47

Quote: Originally posted by Vogelzang  
For almost two decades sinus infections have been going around in my area and I've been trying to find OTC treatments for it.
Google "Grossan Irrigator". Use it twice daily with warm salt water in it and you will stop getting sinusitis.

Vogelzang - 16-7-2012 at 17:08

Here's a good book.

http://archive.org/details/cu31924073971982

http://openlibrary.org/books/OL24187521M/Disinfection_and_th...

Vogelzang - 2-9-2012 at 06:36

Can germicidal inhalers cure pulmonary tuberculosis or at least treat the active form? See the attached references. Resorcin is also known as resorcinol (m-dihydroxybenzene). Hexylresorcinol is a better antimicrobial than resorcinol. Ol. Pin. Sylvest. is oil of Pinus sylvestris (Scots Pine).

http://www.time.com/time/magazine/article/0,9171,719908,00.h...

http://www.thelampworks.com/lw_vapo_cresolene.htm





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[Edited on 2-9-2012 by Vogelzang]

Vogelzang - 2-9-2012 at 07:10

Hexylresorcinol
Monday, Feb. 23, 1925

For ten years, Dr. Veader Leonard and a group of confreres in the Johns Hopkins School of Hygiene and Public Health, Baltimore, have worked with poisons-salts, acids, fats, with blue canisters of strange mineral, with bottles of green, fatal syrup. They sought that latter-day elixir, a fluid deadly to germs, harmless to man, a perfect antiseptic. Last week, came the announcement that they had found and tested such a germicide-hexylresorcinol, 50 times as powerful as carbolic acid.

Dr. Leonard began his experiments with carbolic acid, which, as is well known, kills disease germs and man with equal despatch. To resorcinol (very similar to carbolic acid) certain "fatty" acids were linked. The result was, at first, both an excellent antiseptic and a deadly poison. As the molecular proportion was changed, the antiseptic properties increased, the poisonous effect diminished. At last, with great difficulty, six atomical groups of the acids were united with the resorcinol, hexylresorcinol formed.

Warily, Dr. Leonard administered some of this fluid to a rabbit. The small creature lived. He took some himself, survived. His attendants each swallowed their doses, were not harmed. Then the antiseptic was administered in some cases of kidney disease in the Johns Hopkins Hospital. Within 48 hours, these cases were cured totally and, to all appearances, permanently. A committee of 15 learned gentlemen from the National Research Council was appointed to conduct further investigation.

http://web.archive.org/web/20090502172303/http://www.time.co...

Vogelzang - 2-9-2012 at 07:21

Apocalyptic tuberculosis is spreading throughout the world. Prepare yourselves.


TB timebomb (click to look inside)
http://www.amazon.com/Timebomb-Epidemic-Multi-Drug-Resistant...

Drug-resistant tuberculosis a "time bomb," WHO chief says
http://www.scientificamerican.com/blog/post.cfm?id=drug-resi...

Tuberculosis: "The Captain of All These Men of Death"
http://www.paho.org/English/DD/PIN/Number1_article5.htm

You can see a world-wide map of TB incidence rate next to the grim reapers here. Enlarge to see more detail.
http://cmspath.edu/rfc/lectures11-12/garon/pulmonary/garon-t...

http://www.google.com/#hl=en&sclient=psy-ab&q=Apocal...

[Edited on 2-9-2012 by Vogelzang]

bquirky - 2-9-2012 at 07:48

*yawn* just like swine flu killed us all

triplepoint - 2-9-2012 at 08:12

Quote: Originally posted by bquirky  
*yawn* just like swine flu killed us all


I do not blame you for having a healthy skepticism, but that does not mean there is no cause for concern. It is indisputable that there is a large TB problem. Even if it does not take over the world, it is still worthy of attention. These days, when populations have the ability to move around very freely, someone else's problem can quickly become your problem.

Vogelzang - 2-9-2012 at 10:50

According to this article, this girl had to have a lung removed because of TB. I don't know if they would have done that in the US. They didn't think it was TB at first, but gradually got worse.
http://www.metro.co.uk/news/39729-britain-at-risk-from-tb-ti...

Some people have been known to have been exposed to TB a number of times and never test positive to it. Most people who become infected with it keep it in a latent state usually for years or decades. 10% of the latent TB become active. Latent TB isn't contagious, but it is when its in the active state.

Vogelzang - 2-9-2012 at 12:09

I had a strange dream this afternoon during a nap. I usually get strange dreams after using some piracetam and pramiracetam which I usually use on the weekends for energy. Someone who I thought was someone I knew, but hadn't seen in a couple years pulled out a gun and pointed it at me. I grabbed the barrel and pointed the gun at him. His finger was still on the trigger, but I managed to fire the gun into his chest. An unmarked car came by and 3 cops came out of the car. I had the gun in my hand which I dropped on the ground when the police were looking at me. There was someone else with me who tried to run away. I told the police what happened and that I shot the guy that pointed the gun at me. I was worried about all the legal trouble I'd get into and having to have to go to court. I woke up after that relieved it was just a dream. There must be some Freudian symbolism in it. I was reading about TB for a couple weeks and became fascinated with it while looking at all the pictures on the internet of people in the TB sanatariums, the now abandoned sanitariums, etc. I read through a lot of literature trying to access what the real risk was for me and others in this area.

When I got my change back at a store I went to just an hour ago it said 666 on the cash register and I said "666!". One guy smiled and said to the cashier something in Spanish with the word Diablo in it. Maybe its a preminition of some kind. :o




[Edited on 2-9-2012 by Vogelzang]

Vogelzang - 2-9-2012 at 13:42

Quote: Originally posted by triplepoint  
Quote: Originally posted by bquirky  
*yawn* just like swine flu killed us all


I do not blame you for having a healthy skepticism, but that does not mean there is no cause for concern. It is indisputable that there is a large TB problem. Even if it does not take over the world, it is still worthy of attention. These days, when populations have the ability to move around very freely, someone else's problem can quickly become your problem.


How will it affect your stock portfolio, your retirement?

[Edited on 2-9-2012 by Vogelzang]

bbartlog - 2-9-2012 at 19:35

Those who think that TB will kill us all should first explain why it disappeared from the US and Europe. It was never really vanquished by some aggressive and effective treatment and/or quarantines; it just sort of gradually petered out. I attribute this to the generally good health of the populations of the modern world. Many diseases that cut a devastating swath through malnourished populations just don't have much of an impact here. Look at the death rates for measles in Africa versus the USA, for example.

Vogelzang - 3-9-2012 at 05:14

If you're too lazy to read the links, references and what I wrote, what guarantee do I have that you would listen this time? :P

Vogelzang - 13-9-2012 at 16:06

oregano oil
http://heddwynessentials.com/ooo/index.php?page=home

Vogelzang - 14-9-2012 at 13:04

OPP and TB

http://naldc.nal.usda.gov/download/IND43968019/PDF

Morgan - 15-9-2012 at 05:46

Adverse effects
Fluoroquinolones are considered high-risk antibiotics for the development of Clostridium difficile and MRSA infections.[7][33] A previously rare strain of C. difficile that produces a more severe disease with increased levels of toxins is becoming epidemic, and may be connected to the use of fluoroquinolones.[34] Fluoroquinolones are more strongly associated with C. difficile infections than other antibiotics, including clindamycin, third-generation cephalosporins, and beta lactamase inhibitors. One study found fluoroquinolones were responsible for 55% of C. difficile infections.[35] The European Center for Disease Prevention and Control recommends fluoroquinolones and the antibiotic clindamycin should be avoided in clinical practice due to their high association with C. difficile, a potentially life-threatening super-infection.[8]

The CNS is an important target for fluoroquinolone-mediated neurotoxicity. Adverse event reporting in Italy by doctors showed fluoroquinolones among the top three prescribed drugs for causing adverse neurological and psychiatric effects. These neuropsychiatric effects included tremor, confusion, anxiety, insomnia, agitation, and, in severe cases, psychosis. Moxifloxacin came out worst among the quinolones for causing CNS toxicity.[36] Some support and patient advocacy groups refer to these adverse events as "fluoroquinolone toxicity". Some people from these groups claim to have suffered serious long-term harm to their health from using fluoroquinolones. This has led to a class-action lawsuit by those harmed by the use of fluoroquinolones, as well as action by the consumer advocate group, Public Citizen.[37][38] Partly as a result of the efforts of Public Citizen, the FDA ordered black box warnings on all fluoroquinolones, advising consumers of their possible toxic effects on tendons.[39]
http://en.wikipedia.org/wiki/Quinolone

zed - 26-9-2012 at 16:59

Bacteria develop resistance to some materials, and not to others.

Structurally, Eugenol is a kissing cousin to Phenol (AKA Carbolic Acid). In some regards, its actions resemble Phenol. Phenol, if you have not had the pleasure of working with it, will burn the living crap out of you, and you won't realize it until you notice the giant blisters that have developed on exposed areas. Both caustic and a potent local anesthetic. Not easy to develop resistance to a material that burns your little protozoic ass off.

As for lung removal to combat TB.....Yup, we have been doing it in the U.S. too. Antibiotic resistant strains of TB have forced doctors to remove lung tissue to stop the spread of disease.

Not as big a problem here as in some parts of the world. Apparently, good nutrition, and being caucasian provides reasonably good resistance to the disease.



White Yeti - 27-9-2012 at 14:36

I've done a little reading since I posted this. Here's what I found:
http://www.academicjournals.org/ajb/PDF/pdf2009/6Apr/Oyedemi...
Here's an excerpt from the discussion:

"The effectiveness of γ-terpinene might be the result of its
phenolic structure which interferes with the lipid bilayer of
the outer membranes (Janssen et al., 1987). -terpineol
and eugenol showed similar effect on the lipid content of
cell membrane of both Gram positive and Gram negative
bacteria after 120 min of incubation. All the organisms
tested were very susceptible to the effect of essential oil
components. The different effects observed could be due
to the hydrophobicity of the essential oils components
which enable them to partition the lipids of the bacterial
cell membrane and mitochondria, disturbing the cell
structures and rendering them more permeable (Sikkema
et al., 1994)."

According to another source, a weak solution of eugenol (0.05%) can decimate a population of Bacillus tuberculosis.
http://www.ijrap.net/admin/php/uploads/360_pdf.pdf

I'm not sure how effective eugenol would be for treating TB, because it would get absorbed and metabolised rather quickly.

Speaking of carbolic acid...
http://www.youtube.com/watch?v=eHxhxUXmWe0

I haven't worked with it, but it seems like an insidiously painful compound, since it's both an analgesic and an irritant.

watson.fawkes - 27-9-2012 at 16:37

Quote: Originally posted by zed  
Phenol, if you have not had the pleasure of working with it, will burn the living crap out of you, and you won't realize it until you notice the giant blisters that have developed on exposed areas.
Years ago, I knew a woman who had worked as a PA (physician's assistant) and considered herself perfectly competent to self-administer cosmetic skin peels on occasion. I remember she used retinoic acid, and as I recall at least once a phenol treatment.

FYI, you know.

Sedit - 31-10-2012 at 18:08

Quote: Originally posted by Vogelzang  
Apocalyptic tuberculosis is spreading throughout the world. Prepare yourselves.



Horray.... getting locked up in the county jail paid off for a change. I just got my TB shot!

SO LONG SUCKERS :D

Vogelzang - 3-11-2012 at 02:17

Quote:

She said you’ve had BCG so you won’t have TB. But I did.


http://www.thetruthabouttb.org/stories/natalie

http://www.thetruthabouttb.org/

Russians are given the BCG vaccine several times during their lifetime, but in spite of this Russia has one of the highest rates of TB in the world. Its explained in this book
TB timebomb (click to look inside)
http://www.amazon.com/Timebomb-Epidemic-Multi-Drug-Resistant...


http://www.dailymail.co.uk/news/article-2159855/Alina-Sarag-...

http://www.metro.co.uk/news/39729-britain-at-risk-from-tb-ti...


One third of the human race is infected with TB. 90% of those who are infected with TB keep it in a latent state for the rest of their lives. 10% develop active TB sometime in their lifetimes. It can become active years or decades later, even 40 or 50 years after becoming infected with TB. Latent TB typically has no symptoms and is not contagious. Active TB is contagious.



[Edited on 3-11-2012 by Vogelzang]

Vogelzang - 3-11-2012 at 02:39

2007 tuberculosis scare
http://en.wikipedia.org/wiki/2007_tuberculosis_scare

TB patient charged for not taking meds
http://articles.nydailynews.com/2012-05-17/news/31753428_1_p...

White Yeti - 24-11-2012 at 12:23

Here is a good article on a tuberculosis therapy adjunct. I didn't have time to read through the whole thing, but the results in the abstract and discussion seem very promising.
http://benthamscience.com/open/tonpj/articles/V001/20TONPJ.p...

morganism - 15-12-2012 at 23:27

That thymol is in all those cooking herbs. also some terpenes, and other strong aromatics. Have been studies on them for MRSA too.

Watch the marjoram and oregano oils, they burn skin , especially after a shower ! Havn't tried any essential oil on mucous membranes after that experiment.

Killed the staph better than silver tho, silver just held it at bay.

can irrigate sinuses with colloidal silver, but make sure the particle size is large, it oxidizes with salts quite quickly.
Prob optimize by doing a weak peroxide first.
They use peroxides to cut biofilms, even use it in septic leach lines.

Oscilllator - 17-12-2012 at 21:47

I don't know if anyone else has posted this, but the genes will eventually drop out of the gene pool (assuming there are selection pressures acting on the bacteria). This is because genes take energy to make, and therefore the less genes you have the less energy you require to live, and the more likely you are to survive.

I don't know how fast this will act in a food-rich environment like your mouth, though. Maybe the genes wont drop out at all.

Vogelzang - 7-1-2013 at 17:17

Quote: Originally posted by White Yeti  
Hello everyone,

I started a long term experiment in November of last year to investigate the effect of eugenol (from cloves) on bacterial growth.

I started chewing cloves to relieve gingivitis and I found them to be very effective in mitigating pain.

I didn't stop there, I found the taste of cloves -repulsive to some- quite pleasant. In addition to relieving pain, cloves also deter bacterial growth and are extremely effective against the buildup of plaque. I would also like to mention that cloves did not substitute regular oral hygiene practices, they served as a supplement (rather like gum or mouthwash).

As with all good things in life, there comes a point where all this comes to an end. Bacteria, pesky as they are, always evolve to conform to environmental disturbances.

I was wondering....

If I abruptly switched from cloves, to oregano for example (which does not contain eugenol), would the bacteria be resistant to antibacterial substances in both cloves and oregano? Or would the genes for eugenol resistance slowly drop out of the gene pool, at which point I would be able to use cloves again?

I understand this is a rather strange post, but haven't found any documentation on bacterial evolution as a response to an abrupt switch from one antibacterial substance to another.

Any thoughts?



Try this http://www.actfluoride.com/
Rite Aid has a lower cost version. Fluoride solution seems to have some antiseptic activity when I use it. I haven't had any cavities in years which I believe is due to the fluoride rinse as well as brushing and flossing regularly. Also, look at ST 37 here http://www.amazon.com/ST-37-ANTISEPTIC-LIQUID-Size/dp/B000NU...

Some side effects are discussed here
ARTICLE | March 25, 1933
DERMATITIS FROM THE USE OF HEXYLRESORCINOL SOLUTION S. T. 37: ACQUIRED SENSITIVITY
Clyde L. Cummer, M.D.
JAMA. 1933;100(12):884-885. doi:10.1001/jama.1933.27420120001009
ABSTRACT
http://jama.jamanetwork.com/article.aspx?articleid=242232

I found a 1934 ST 37 Ad on Ebay.


HexylresorcinolAd1934.JPG - 379kB

[Edited on 8-1-2013 by Vogelzang]

AJKOER - 27-2-2013 at 17:52

OK, does anyone know how colloidal Silver kills germs and viruses?

A bit old school (used before the invention of antibiotics) but some recent interest in it.

In the case of Zinc, it apparently disrupts the reproductive cycle.

I guess it is harder for a bug to re-invent its biochemistry to be immune from a heavy metal.

pneumatician - 31-10-2014 at 17:41

perhaps here some info :)

http://g2cforum.org/index.php/list/other-alternatives/28556-...

Chemosynthesis - 3-11-2014 at 02:38

Quote: Originally posted by AJKOER  
OK, does anyone know how colloidal Silver kills germs and viruses?

A bit old school (used before the invention of antibiotics) but some recent interest in it.

In the case of Zinc, it apparently disrupts the reproductive cycle.

I guess it is harder for a bug to re-invent its biochemistry to be immune from a heavy metal.
http://www.ncbi.nlm.nih.gov/m/pubmed/15114827/

macckone - 3-11-2014 at 10:24

Silver nitrate eye drops were commonly used in newborn's eyes as an infection prevention measure. Now they tend to use erythromycin as a more effective form. However, colloidal silver is one of those "sure it might work against something but it isn't likely to be what you have" things.

As to the original discussion of antibiotic resistance, genes for antibiotic resistance are selected against in an antibiotic free environment. That doesn't mean they magically disappear but over time without the use of particular classes of antibiotics bacteria do indeed become more susceptible to them and sometimes the genes even disappear from the particular pool of bacteria.

Due to the use of a wide range of antibiotics in both feed lots and hospitals we are seeing more multiple drug resistant strains. The heavier duty antibiotics such as methicillin are only used in hospitals so the most dangerous strains that are resistant to the widest range of antibiotics are generally in hospitals.

Chemosynthesis - 3-11-2014 at 11:06

Oscillator mentioned energy of replication as one aspect of selection against antibiotic gene replication in the absence of antibiotics, but speed of replication is also a selective force.

Bacteria with the smallest genomes tend to replicate fastest, and so the smallest genome among otherwise equally fit bacteria is likely to outcompete neighboring strains, producing more offspring, which is the standard measure of fitness. And in case anyone considers plasmids, bear in mind plasmid replication still requires polymerase, which is a scarce protein that could otherwise hasten non-plasmid replication.

JAVA - 10-11-2014 at 06:35

MRSA (Methicillin-resistant Staphylococcus aureus) is such an example of a bacteria which doesn't react on antibiotics.

Penicillin normally blocks the enzyme transpeptidase in a irriversible way. This in turn prevent that the new peptidoglycan cell wall could be formed after the division and the transfer of new DNA to the other future cell of the bacteria.

Penicillinase or beta-lactamase are a huge group of different enzymes produced by these resistant bacteria. These enzymes are responsible for the hydrolytic cleavage of penicillin to penicilloic acid.

The interesting thing is that "Clavulanic acid" is a penicillinase inhibitor but they will probably not act on all the types of beta-lactamases. Then, further research is needed to make derivates of clavulanic acid and formulate it with these life-curing antibiotics.


Another strategy to reduce the problem of penicillin resistance is to use probiotics which are the good bacteria that knock down the pathogenic bacteria. (nutrient competition)

There are other antibiotics as well, like the sulfonamides.

For MRSA a very strict quarantine is needed to prevent that this particular bacteria go from one infected hospital to another.

Chemosynthesis - 10-11-2014 at 07:35

Quote: Originally posted by JAVA  
MRSA (Methicillin-resistant Staphylococcus aureus) is such an example of a bacteria which doesn't react on antibiotics.
MRSA is generally vulnerable to vancomycin, the standard/ preferred treatment for methicillin resistant staph. Quarantine is often more to prevent VRSA mutation, though nosocomial infections do seem to have brought about communal staph infections which are thought to evade decolonization via reservoirs in the nasal cavity.

XDR-TB is probably a better example of antibiotic resistance, being a type of MDR-TB (extreme drug resistant and multiple drug resistant m. tuberculosis, respectively.).
Mycobacteriophage, while not often considered probiotics, are also a promising treatment that waned in research popularity after the emergence of sulfonamides, and are seeing more favor due to XDR-TB.

macckone - 10-11-2014 at 11:03

One of the biggest problems with antibiotic resistance is that
pharmaceutical companies are not developing new ones.
Since these drugs would only be used against resistant strains
the market is very small and not considered profitable enough
to devote resources necessary to develop new drugs.
As antibiotic resistance increases, this would change as the
potential market expands.

Chemosynthesis - 10-11-2014 at 15:06

There is an emerging market share in novel antibiotics with several in clinical development, as well as incentives under the GAIN Act of 2012, but proper use of combinatorial antibiotic therapies make it a little less incentivized than other drugs, as well as "orphan drug status" in some developed countries, which means diagnoses of specific antibiotic resistance drugs still doesn't affect enough patients to make focus on them more than they are currently. In countries other than the U.S., the governments tend to set prices, which means if U.S. markets can't offset more of the fixed costs (billions), there isn't much financial incentive to do so since you never return your investment. That does skew drug development somewhat towards U.S. markets solely from a cost perspective since price fixing doesn't occur here.

Part of the problem is it takes roughly 5k initial screens to find a hit which may end up optimized into a lead compound, and once pursued only 1 in 5 drugs in clinical trials is accepted by the FDA... roughly 12 years later. Drugs with new targets or modes of actions (such as are required here to avoid cross resistance/desensitization) average on the longer end of drugs developed because the FDA doesn't want anyone marketing something without knowing how it works, which is useful in predicting toxidromes with improper dosing or off-target effects.. That development time lag really shows. Edit: and I forget the substantial failure state between leads and clinical trials. Not insignificant either. But there definitely are some antibiotics in development at this moment.

In fact, I see 3 that just met FDA approval this year: Dalbavancin, Tedizolid, and Oritavancin. Granted, the *vancins are similar, and have a MoA akin to vancomycin, which reduces novelty somewhat. Might get lucky with the little time we have left in the year and crank out some of the PIII candidates for clinical use (I see 7 in development, so assume 1 makes it to market... extremely conservative estimate based off of most drugs failing late trial stages when population diversities increase, which is not incidentally after drugs have cost the most to develop).


[Edited on 11-11-2014 by Chemosynthesis]

macckone - 10-11-2014 at 21:16

Will these new drugs really help with antibiotic resistance since they are in the same class and have similar action?

plante1999 - 10-11-2014 at 21:24

Organism manage to survive disinfection because a few of the thousands present a place got a gene that makes them survive. But, wouldn't it be possible to use something that would sort of destroy the DNA/RNA. I agree it might be of some risk for the host, but in theory, no genes can really protect from something that destroy genes.

Chemosynthesis - 10-11-2014 at 22:32

Quote: Originally posted by macckone  
Will these new drugs really help with antibiotic resistance since they are in the same class and have similar action?
They can. I don't know if they will, but efficacy may be increased enough such that resistance is diminished, or safety profiles and cost may allow higher dosing which is more difficult to become resistant to. It really depends on the particular target and the drug itself. Some target signaling cascades are very complicated, and small ligand changes may affect the kinetics of effector and regulator proteins downstream, which diminish side effects from divergent signaling pathways, receptor/ligand promiscuity, cross tolerance, etc.

Additionally, pharmacokinetics and metabolism may allow more convenient dosing maintenance which can lead to better outpatient compliance. Sometimes the dosing allows for easier co-administration, chemical compatibility in an IV, or even oral bioavailability for outpatient compliance (since oral formulation is easier than injection).
Quote: Originally posted by plante1999  
Organism manage to survive disinfection because a few of the thousands present a place got a gene that makes them survive. But, wouldn't it be possible to use something that would sort of destroy the DNA/RNA. I agree it might be of some risk for the host, but in theory, no genes can really protect from something that destroy genes.
It's important to distinguish between antibiotics, antiseptics, disinfectants, sterilization agents, etc. Actually, organisms can modify to transport disinfectants out of the cell, or change membrane thickness/permeability. It is surprisingly common, even the DNA or RNA itself isn't directly causing the resistance (it does so through the central dogma). http://www.sciencedirect.com/science/article/pii/S0964830503...

Anything potentially mutagenic, damaging DNA, will never be used in people as an antiseptic because you have cumulative risk of carcinogenesis, which is a health, legal, and ethical concern. Same reason no dose of ionizing radiation is considered safe/beneficial if avoidable. This prevents safe drug delivery to your target microbe, and even with release inside of a microbe... dead membranes are permeable, exposing your patient. However, there are antibiotics that inhibit DNA replication by specific bacterial DNA polymerase subunits, transcription, or bacterial ribosome translation specifically enough to be safe for use in people.

macckone - 10-11-2014 at 22:57

Oxyplatin destroys DNA but it isn't useful as an antibiotic but is a useful chemo drug. However some bacteria are susceptible especially intestinal fauna.

confused - 11-11-2014 at 07:57

There are antibiotics that can affect the replication of the bacteria by

-inhibiting transcription, thus preventing mRNA and inhibiting protein synthesis

-inhibit the activity of DNA/RNA grases/topoisomerases, preventing polymerase from replicating the DNA

for the most part, most antibiotics affect some aspect of cell wall synthesis, however, there are antibiotics such as Myxopyronin, which inhibit bacterial RNA polymerase.

one method to decrease antibiotic resistance, is to use an inhibitor for the protein that causes the antibiotic resistance, such as clavulanic acid which binds to beta-lactamase, which some bacteria produce to break down beta-lactam antibiotics.

Chemosynthesis - 11-11-2014 at 23:15

Quote: Originally posted by confused  
There are antibiotics that can affect the replication of the bacteria by

-inhibiting transcription, thus preventing mRNA and inhibiting protein synthesis

-inhibit the activity of DNA/RNA grases/topoisomerases, preventing polymerase from replicating the DNA

for the most part, most antibiotics affect some aspect of cell wall synthesis, however, there are antibiotics such as Myxopyronin, which inhibit bacterial RNA polymerase.

one method to decrease antibiotic resistance, is to use an inhibitor for the protein that causes the antibiotic resistance, such as clavulanic acid which binds to beta-lactamase, which some bacteria produce to break down beta-lactam antibiotics.
True, particularly for fluoroquinolones on gyrase/topos, which I failed to mention.
More sites of action as well. Really ridiculous how many there are. If it's different from a human, something likely targets it in concept.
Quote: Originally posted by Chemosynthesis  
However, there are antibiotics that inhibit DNA replication by specific bacterial DNA polymerase subunits, transcription, or bacterial ribosome translation specifically enough to be safe for use in people.


Small 30S ribosome targeting antibiotics include: neomycin, gentamycin and paromomycin.
Large 50S include erythromycin.

Little_Ghost_again - 25-11-2014 at 04:44

Not sure how relevant this but I often wonder why the use of phages is not more widely used for antibiotic resistant microbes, although my own view is this is cost based. More money to be made with tweaking antibiotics.

EDIT
I did a quick search
PMCID: PMC4072922 Natural solution to antibiotic resistance: bacteriophages ‘The Living Drugs’
Havnt read it yet but looks interesting.

[Edited on 25-11-2014 by Little_Ghost_again]


For a good general look at resistance this looks to have some good info PMCID: PMC2937522
its a pretty big paper thouh


[Edited on 25-11-2014 by Little_Ghost_again]

Chemosynthesis - 25-11-2014 at 05:38

I actually have some professional experience with phage. It was looking big in Easter Europe and Russia back around the turn of the (technically previous now) century, however the emergence of sulfonamides allowed much cheaper and easier scaled production (at the time).

Antibiotics are actually fairly unprofitable. Phage are a lot cheaper to produce at marginal cost than antibiotics, and regulation is kind of burdensome since they have been treated like antibiotics.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400130/

Little_Ghost_again - 25-11-2014 at 13:03

Quote: Originally posted by Chemosynthesis  
I actually have some professional experience with phage. It was looking big in Easter Europe and Russia back around the turn of the (technically previous now) century, however the emergence of sulfonamides allowed much cheaper and easier scaled production (at the time).

Antibiotics are actually fairly unprofitable. Phage are a lot cheaper to produce at marginal cost than antibiotics, and regulation is kind of burdensome since they have been treated like antibiotics.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400130/


I have seen a TV program a couple of years ago, it was based around a eastern European country (I cant remember which), The hospital had a lab where they would go with a glass jar to the sewer outlet and look for phages in the effluent, it had great promise for MRSA in the hospital there, I also remember it saying that phage treatment was more common in Veterinary uses.
There are some great papers on phages, really fascinating. I am still not sure what the OP is trying to do?? Is he trying to grow it or just looking into its production, maybe for some kind of school project??

My own view on drug production is a bit conflicting, on the one hand you have massive expense of trials etc that raise the cost of making a new drug, then on the other you want a safe drug... Then you have the situation where I am taking part in a trial for a new cancer drug, I may or may not be on the real drug or the placebo (judging by the improvement I think i am on the drug).
I also think alot of anti Biotic resistance is down to the antibiotics used in food production (see ref in earlier post for citation).
I have been lucky enough to see home scale, lab scale, and a trip around industrial scale bio reactors for M.O's, each completely different.
Which phage did you work on?

Chemosynthesis - 25-11-2014 at 13:27

Good question on the OP. Kind of an aside, but I agree about antibiotic use in veterinary CAFO/food industry use.

It's kind of awkward in a sense, though understandable, that so much effort goes into pre-clinical and clinical screening for toxicities when the most frequently occurring drug side effects and adverse reactions are those most commonly prescribed in hospitals (not to be confused with DAWN emergency room statistics). The sheer number of administrations and the law of averages is what leads to clinical pharmacology problems.

As far as phage, I'd prefer not to say specifically because I am still waiting on publications in various stages of submission. I've worked on 4 or so, having discovered one, which actually isn't as prestigious as I had hoped since apparently high school children are just as accomplished in that particular metric.

Little_Ghost_again - 25-11-2014 at 18:26

Quote: Originally posted by Chemosynthesis  
Good question on the OP. Kind of an aside, but I agree about antibiotic use in veterinary CAFO/food industry use.

It's kind of awkward in a sense, though understandable, that so much effort goes into pre-clinical and clinical screening for toxicities when the most frequently occurring drug side effects and adverse reactions are those most commonly prescribed in hospitals (not to be confused with DAWN emergency room statistics). The sheer number of administrations and the law of averages is what leads to clinical pharmacology problems.

As far as phage, I'd prefer not to say specifically because I am still waiting on publications in various stages of submission. I've worked on 4 or so, having discovered one, which actually isn't as prestigious as I had hoped since apparently high school children are just as accomplished in that particular metric.


Fair enough, let me know when you have published though! I would love to read the papers. Publishing is a funny beast, like with my dad if does something gets excited then cant say much until the work gets published! I am working on getting my style right etc etc and hope next year to publish something, it might not happen but would be cool to do some original work and get it published.
Discovering a phage is cool! Having seen the work that goes into the isolation etc its no easy task. did you get to take a look with a SEM?
Microscopy is a real passion but I am still very amateur at slide prep etc, takes a good while to get the staining and mounting right, and although there is a microtome here I am not allowed near it, but then again having seen what the blades cost.........
Glasgow uni has some really cool electron microscopes, I have been a few times and had a go with there old SEM. maybe one day I will make enough to own one :D

confused - 26-11-2014 at 07:39

Quote: Originally posted by Little_Ghost_again  
Microscopy is a real passion but I am still very amateur at slide prep etc, takes a good while to get the staining and mounting right, and although there is a microtome here I am not allowed near it, but then again having seen what the blades cost.........


Well you might be able to make do without a microtome if you have a scapel and slide it extremely thinly. Im assuming you're refering to a normal histology H&E stain type of slide.

You might want to take a look at this though
[A novel method for preparing histology slides without a microtome.]
http://www.ncbi.nlm.nih.gov/pubmed/12479353

[Edited on 26-11-2014 by confused]

[Edited on 27-11-2014 by confused]

Chemosynthesis - 26-11-2014 at 07:41

Publishing sure is. I think the hardest pre-submission part is sometimes consensus among co-authors, or knowing when to hand it over to another party for opinions when you get stuck. I hope you do get to publish! You should take a lot of pride in your work.

I actually did get to isolate phage, grow out batches, set up my samples for the electron microscope techs (saw the image on a screen, but didn't operate it), try activating/deactivating lytic cycles, did some genomic work, etc.

Check Ebay. There is an untested Amray SEM going to 99 cents (USD) with two days to close. Shipping would be expensive for you, but perhaps you could get one soon.

Tsjerk - 26-11-2014 at 09:29

I think the reason phages are not used that often in medicine is because bacterial resistance is very, very easily acquired. In a population of 1 billion, the change of one being immune is about 1%. In a common infection that is almost a change of 100%. Especially with the very strong selection pressure of the phage itself this excludes phages from being used as a medicine.

The problem is that resistance against phages can be acquired trough down-regulation of non-essential proteins. All regulation is, randomly, up and down regulated by different bacteria within the population. They do this to make sure at least one of them survives... As they are all one in means of genes this gives the best change of survival of the genes (selfish gene theory).

Conventional antibiotics work on essential systems, making it a bit harder to gain resistance.

Edit: Definitely recommended literature: The selfish gene, Richard Dawkins 1976; explaining why altruism exists.

[Edited on 26-11-2014 by Tsjerk]

Little_Ghost_again - 26-11-2014 at 10:31

Quote: Originally posted by Chemosynthesis  
Publishing sure is. I think the hardest pre-submission part is sometimes consensus among co-authors, or knowing when to hand it over to another party for opinions when you get stuck. I hope you do get to publish! You should take a lot of pride in your work.

I actually did get to isolate phage, grow out batches, set up my samples for the electron microscope techs (saw the image on a screen, but didn't operate it), try activating/deactivating lytic cycles, did some genomic work, etc.

Check Ebay. There is an untested Amray SEM going to 99 cents (USD) with two days to close. Shipping would be expensive for you, but perhaps you could get one soon.


Thanks for the paper! The scope is cool, but again it isnt the cost of getting one its the cost of running one lol. all that gold sputtering etc etc, We run on generators for electric, I wonder how much juice a SEM would use :D.
Bacteria are far less likely to aquire resistance to a phage than a drug, a drug enters the cell wall etc etc a phage (depending) looks for certain proteins or whatever (depending on the mechanism like lock and key etc etc), so I would be doubtful that bacteria would develop resistance to phages quicker than drugs.
Again like you cited the selfish gene...........I dont think much of that book but if you use it as an example then you would also need to apply the principle to the phage, so as the organism changed so would the phage.
Take MRSA some lab strain are just about totally resistant to antibiotics including the last chance saloon vancamicine, and yet there are still phages that will attack it.
Both Ireland and a eastern European country (I cant remember which one) have had good results treating MRSA with phages.
I agree drugs target critical systems but first the drug has to enter the organism, in many resistant cases the organism has changed the cell membrane and stops the drug or class of drugs, many phages just need the protein or whatever present, zoom in land and drill down into the bug (not all and way over simplified).
So before I get picked up on it, no I dont mean actually drill into it, but some look like a space ship and have a kind of spring loaded mechanism that fires down into the cell unloading its payload.
Anyway thanks for the link I might give that a try! I did find a cheap microtome but it needed a new blade, the super duper diamond ones are a little expensive and fragile, but seeing a cell nucleus cleanly cut in half shows you why they cost what they do.
Yeah and getting a tech to let you twiddle the knobs is no easy task! they all seem to be touchy with there scopes

Chemosynthesis - 26-11-2014 at 12:06

Never said anything about running an SEM at home, just getting one ;).

I have some phage papers in a filing cabinet around here on the selective pressures or likelihood of resistance somewhere. It definitely is considered more difficult to become resistant to a phage. Proper antibiotic use and dosing greatly diminishes the occurrence of resistance, and there are some potential VRSA treatments, but the specificity of phage also allows good drug targeting without impacting as much of the microbiome.

Little_Ghost_again - 16-12-2014 at 21:12

One other thing I came across the other day, until pretty recently it was thought viruses did not exist in the marine environment, but turns out its full of them in the upper couple of mm of water and nearly all are actually phages!
Oh the ref for that is general microbiology fifth ed Roger Y.Stainer .

Chemosynthesis - 16-12-2014 at 22:36

Sounds like the Global Ocean Sampling Expedition.

Also, the FDA did happen to approve a fourth antibiotic for limited use before the new calendar year: ceftazidime-avibactam.

Little_Ghost_again - 17-12-2014 at 05:39

Quote: Originally posted by Chemosynthesis  
Sounds like the Global Ocean Sampling Expedition.

Also, the FDA did happen to approve a fourth antibiotic for limited use before the new calendar year: ceftazidime-avibactam.


I have been reading the paper for that, I am not so sure why the rush with it? Interesting though that its so highly selective.

I am going to Glasgow University tomorrow with my dad, they are shutting down for Christmas and one the labs used for teaching is due for a DEEP CLEAN, so as its not going to be used for a bit and is getting gassed soon, I have been offered the chance to go and try some stuff out, I mentioned to chris (guy who operates the electron scopes) that I like phages, he has promised to show me some under both scopes! I love the structure and simple beauty of them.

Millions of preventable deaths planned

franklyn - 25-7-2015 at 05:44

We are now on the brink of entering into a new era of retro-medicine. Due to the evolution of antibiotic resistant bacteria , infections up till now easily cured with a few pills will become rampant once more. Treatments for infections that have not been practiced in over seven decades will soon become common again. Disfigurement and death due to inadequacy of surgical excision of infected tissue will mount into unheard tolls. Each year, an estimated 2 million people in the U.S. are infected with antibiotic-resistant bacteria of which at least 23,000 die , making this the primary emerging public health issue in the United States. Worldwide it's anybodies guess what the count will come to in succeeding years.

The ever expanding list of resistant infectious pathogens include , Tuberculosis , Staph most commonly MRSA , E-Coli , various other pathogenic bacteria's that have become difficult to treat. Recently evolved Acinetobacters superbugs are much more dangerous than the original bacteria. Brought back by wounded soldiers in Iraq , current versions have thousands of mutants that thrive in the jagged wounds made by modern weapons growing stronger with antibiotic exposure , resist most treatments , and can survive for weeks on hard surfaces like counters and equipment with no food. The consequence of acquiring an Acinetobacter infection ranges from a few more weeks in the hospital to severe suppression of the immune system that can exacerbate other illnesses and lead to death. Unless they are screening for routinely , doctors may not even know if a patient has been infected.

KPC is a genetically conferred attribute present in many infectious bacterial strains making them highly resistant to conventional antibiotic treatment. NDM-1 is a gene that turns bacteria resistant to almost all antibiotics. The resistance gene can pass from bacteria to bacteria, making common treatable infections suddenly untreatable. These occur as Multi , Extensive , and Pan drug resistant variants the Pan being entirely untreatable with drug regimens. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075864 , http://wwwnc.cdc.gov/eid/article/21/6/14-1504_article ,
http://www.pbs.org/wgbh/pages/frontline/health-science-techn...

It can easily cost up to a billion dollars to bring a new drug to the market. Drugs to treat chronic diseases that you must take for the rest of your life have the greatest return on investment. Antibiotics which are taken only for a short course of maybe a couple of weeks and then you stop , have just marginal profitability. Motivated by maximizing profit the dominant pharmaceutical companies have ended research and development on antibiotics , at precisely a time when new drugs to treat infectious disease are most needed. In March 2015 a feckless ' plan of action ' was enacted to play up administrative responses. Notably lacking is any provision to develop the needed new antibiotic treatments. QUOTE :
" Despite the urgent need for new antibiotics, the number of products in the drug-development pipeline is small and commercial interest remains limited." " Advancement of drug development will require intensified efforts to boost scientific research, attract private investment, ". In other words we're all going to be managed to death. Well a plaque on their house. Whatever comes around goes around. http://www.whitehouse.gov/sites/default/files/docs/national_...

These are the facts , draw your own conclusion , but if you think this just happened unexpectedly , you must believe everything people tell to you.
This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction.

Superbugs Resistant To Antibiotics
http://www.youtube.com/watch?v=JW1T_RP-1rQ

.

[Edited on 25-7-2015 by franklyn]

ziqquratu - 26-7-2015 at 16:36

So what do you do about it, franklyn? Have you ever failed to complete a course of antibiotics prescribed by a doctor? Have you ever taken antibiotics for a viral infection (cold, flu, ear infection, etc.)? Do you purchase meat from producers who overuse antibiotics? Do you use antibiotic hand washes for general purposes around your home? All of these things are amongst the primary reasons for the development of antibiotic resistance. They are also the reason that, even if new drugs come to market, resistance to those will often come about within just a few years.

To my knowledge, 2005 was when the most recent new class of antibiotics was introduced to the market - tigecycline, which was specifically designed to overcome the then-current mechanisms of resistance to tetracyclines. And yet, even before it was developed, there were species - some Pseudomonads, for example - which already had a mechanism by which they could be resistant (an efflux pump). Ultimately, all new antibiotics are stopgaps - resistance WILL emerge sooner or later (usually sooner - and the more the drug is used, the faster resistance will emerge), and may already exist anyway. For perspective, E. coli replicates every 20 minutes, and about 1 in 1000 bacteria will experience a mutation in every generation, and a colony a couple mm in diameter contains a few billion cells. At that rate, how long do you think it will take for a mutant to spring up when there's a strong selection pressure around?

As for "evil pharma, who's only interested in making a profit" - yuh, that's what companies do. I would have thought that you, with your libertarian, capitalist, anti-socialist bent, would know that, in a free market, a business should and will do whatever it is allowed to do in order to maximise profits. Antibiotics are NOT profitable drugs in the first place - people take them for a short period of time, often just a few days, rarely more than a couple of months - and any new antibiotic which reaches the market will also be used only as a last resort in order to slow the emergence of resistance to the drug. Despite that, antibiotics are no cheaper to develop than any other class of drug. So why should any company do something that is against its interests? I mean, a company taking on a burden in order to do something which has limited potential for profit (in fact, probably a financial loss) just because it's a "benefit to society" - isn't that scarily like socialism?

Of course, we could push for our governments to provide incentives to drug manufacturers - extended patent protection, perhaps, or even simply chipping in on some of the R&D costs - but then again, the government should probably keep its nose out of the market and not "prop up" unprofitable sections of industry.

A lot of public institutions have people who work towards the development of new antibiotics. Of course, funding for science - particularly the type of "low level" R&D involved in early-stage drug discovery - is getting harder and harder to come by, since funding basic research is no longer seen as a public good, and besides, those dodgy academics are just going to sell their discovery to big pharma and pocket the cash anyway, so why should the public fund that?

As for "This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction." Sure, that's possible - insofar as there are no formal logical fallacies that I can see in the statement. And after all, a pandemic of antibiotic resistant infections would probably do a reasonable job of reducing the population. Also, NDM-1, the big scary at the moment, was named for New Delhi, where it was first isolated - and India does have a big population...

Of course, it could also just be a consequence of human nature. As you said, we have known for a long time about the emergence of antibiotic resistance - the first report of antibiotic resistance came about a year after the first antibiotic. And yet, stubborn agribusinesses refuse to improve their practices in order to reduce their reliance on antibiotic prophylaxis or as growth promoters (hey, why should they? I mean, sure, society would benefit, but the companies would lose money. You just keep your socialist nose out of it and let the market take care of... oh); patients still whinge that they "need" antibiotics for their cold, because they "know [their] bodies" and "this is the worst cold ever, it must be something else". Then when they get better after two days (because that's how the common cold works), they "don't need these antibiotics any more," so they tuck the half pack back in the cupboard for next time they get the sniffles (because hey, they "worked" for this cold, so what do those doctors know, eh?). Heck, I've personally seen someone give a friend their leftovers, because "this helped me, you should try it."

So, the problem COULD be a concerted effort at population reduction; alternatively, it COULD be the well documented effects of greed, stubbornness and cognitive biases.

blogfast25 - 26-7-2015 at 17:04

Quote: Originally posted by ziqquratu  


As for "This had been anticipated , considered , and deliberately chosen as a course to follow to achieve radical population reduction." Sure, that's possible - insofar as there are no formal logical fallacies that I can see in the statement. And after all, a pandemic of antibiotic resistant infections would probably do a reasonable job of reducing the population. Also, NDM-1, the big scary at the moment, was named for New Delhi, where it was first isolated - and India does have a big population...



How about, who would benefit from such a 'cull'? (The idea of a deliberate cull is of course the stuff Alex Jones/Jeff Rense websites is made of, in itself a good reason to distrust these 'theories'). And who's the Bond Villain in this piece? :o

To avoid catastrophe and assuming Big Pharma sees no profit motive in solving the crisis, then logically Governments will have to take action (on several levels). A political illiterate would protest such a benevolent intervention with the usual hysterical shrieks of 'That's Socialism!' but one must hope the ADULTS with cooler heads will prevail.

[Edited on 27-7-2015 by blogfast25]

watch the next 3 minutes

franklyn - 29-7-2015 at 01:44

http://www.youtube.com/watch?v=Hgyztsj7O6M&t=50m35s

blogfast25 - 29-7-2015 at 05:44

Quote: Originally posted by franklyn  
http://www.youtube.com/watch?v=Hgyztsj7O6M&t=50m35s


And NUTTIN' about teh chemtrailz! Very disappointing...





franklyn talkin conspiracy.jpg - 28kB

Bot0nist - 29-7-2015 at 06:58

The truth behind every Internet conspiracy theory. A good video by "Cracked"
https://youtu.be/8HezndRzDBQ

blogfast25 - 29-7-2015 at 09:56

Quote: Originally posted by Bot0nist  
The truth behind every Internet conspiracy theory. A good video by "Cracked"
https://youtu.be/8HezndRzDBQ


Good vid!

Flat Earth Society: Going Tinfoil since 2004!

I've said before

franklyn - 29-7-2015 at 15:16

Truth is elemental , it cannot be created nor destroyed , it can only be suppressed or adulterated.
Precluded by it's nature from doing the former , your only recourse is to perpetrate the latter.

Availed to you are tired old communist disinformation methods which identify you as what you are
http://www.sciencemadness.org/talk/viewthread.php?tid=22410#...

National Security Study Memorandum 1974 , alias Kissinger Report shown before here _
http://www.sciencemadness.org/talk/viewthread.php?tid=19102&...
is your shadow government's ( certainly not mine ) institutional excrement.
Readily available from the Nixon Library ( NSSM 200 )
http://www.nixonlibrary.gov/virtuallibrary/documents/nationa...

Implications of Worldwide Population Growth for U.S. Security and Overseas Interests
http://www.nixonlibrary.gov/virtuallibrary/documents/nssm/ns...
FULL TEXT
http://pdf.usaid.gov/pdf_docs/PCAAB500.pdf

The casual reader must make a judgement. Do they believe what they can see for themselves ,
or do they believe what others tell them about what they don't want them to see.
The last word from the same source _
http://www.youtube.com/watch?v=Hgyztsj7O6M&t=1h26m18s

.

aga - 29-7-2015 at 15:21

To be fair, the human population is out of control.

Nature was already taking action, long before any 'plans' were conceived.

Only China has ever had the balls to face the problem head-on.

The North (including Australia) opted for Junk Food as the main birth/death rate modulator.

The South had little choice and ended up with war/disease/famine.

All still not working out very well though, so expect Severity.

It dunt look good peeps.

[Edited on 29-7-2015 by aga]

blogfast25 - 29-7-2015 at 15:34

Quote: Originally posted by franklyn  
Truth is elemental , it cannot be created nor destroyed , it can only be suppressed or adulterated.



Once again it's you that accepts low level sources as if they are Gospel truth, with no room for error, doubt or interpretation.

You find an 'explanation' for 'something' on the Tinkerwebs and your critical faculties leave you altogether. We've been here before, see your water car thread, aka 'you can't argue with success' (LOL).

I've read more interesting stuff on David Icke's site, franklyn.

Your main raison d'être on this forum seems to be to annoy others with ever more third rate phantasmagoria...

[Edited on 29-7-2015 by blogfast25]

crazyboy - 29-7-2015 at 18:30

Well this devolved quickly.

There are many mechanisms by which bacteria can become antibiotic resistant but I think the scariest is upregulated efflux pumps which pump out antibiotics with little specificity. There have been investigations into efflux inhibitors but ultimately bacteria can and will become resistant to these if they reach the market.

Personally I don't see this problem going away soon. The solution is not completely straight forward but would certainly involve a dramatic decrease in antibiotic consumption. Drug discovery is too slow and expensive to remain effective in such an unprofitable market. If there is a solution I imagine it will rely on phages, bacterial analogs of siRNA, or CRISPR interference because those platforms could easily be modified to different targets across species and rely on DNA or RNA synthesis rather than organic chemistry. Of course just as bacteria have developed nonspecific resistance to many classes of antibiotics it is not unforeseeable that they could develop nonspecific resistances to these new treatments.

Perhaps refraining from using certain classes of antibiotics globally could reduce selection pressure for resistance to that particular antibiotic and we could cycle in this way repeatedly. Probably not feasible due to the limited classes and the necessity for as wide a range as possible especially in the areas with high rates of multiple resistant strains such as hospitals.



ziqquratu - 29-7-2015 at 19:06

Quote: Originally posted by crazyboy  
Well this devolved quickly.


Seems to be happening a lot lately... maybe I'm just paying more attention to it, though.

I tend to agree - traditional antibiotics will retain their place as a mainstay of therapy, but new mechanisms based around phages, for example, will have to be developed to treat highly resistant infections. Phages, in particular, have the advantage that the virus should, or average, evolve faster than the bacteria (due to shorter generation time and larger copy number), so development of resistance should be very slow.
Quote: Originally posted by crazyboy  

Perhaps refraining from using certain classes of antibiotics globally could reduce selection pressure for resistance to that particular antibiotic and we could cycle in this way repeatedly. Probably not feasible due to the limited classes and the necessity for as wide a range as possible especially in the areas with high rates of multiple resistant strains such as hospitals.


The problems with that are many, unfortunately. In addition to the considerations you've outlined, antibiotic resistance will (probably) never disappear simply because the selection pressure does - the genes for most resistance mechanisms can simply be turned off, and thus cost the organism almost nothing in terms of fitness, but remaining in the gene pool should the selection pressure return. In addition, many mechanisms target multiple classes of antibiotics - efflux pumps, which you identified, being a major example of this - so sequestering some drugs would have no effect on that type of resistance.

The solution to the problem is complex and requires multiple approaches. New drugs would certainly be welcome, and whole new types of therapy (phages etc.) will also likely be required. Improved prescribing and patient compliance (which requires education of doctors and patients) are critical, as is elimination of antibiotic misuse in the agricultural sector. This is also an area where your suggestion to reserve particular antibiotics could work - we can make sure that animals never receive certain antibiotics (or even classes of them), thus reserving those drugs for human infections and, hopefully, slowing the development and spread of resistance.

The development of better diagnostic tools (which would allow for better prescribing choices), and research to enable more effective use of antibiotics (for example, what dose is effective and how long should treatment go on for) or to improve decisions about whether antibiotics are required at all (for example, I understand that there's mounting evidence against the need for or effectiveness of antibiotic prophylaxis prior to many types of surgery) are all going to be important, too.

franklyn - 4-8-2015 at 12:30

The alternative , Phages are natually occuring agents and so do not require the same testing as drugs.
Since western medicine is wedded to pharmaceutical usage this treatment is uninvestigated.

http://en.wikipedia.org/wiki/Phage_therapy
http://www.nature.com/news/phage-therapy-gets-revitalized-1....
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351
http://www.themadscienceblog.com/2013/09/phage-therapy-old-i...
http://bullshitcitynorth.blogspot.com/2010/12/phage-therapy-...
Quote: Originally posted by aga  
To be fair, the human population is out of control.


Oh my , aga , incredibly this myth persists.

http://www.sciencemadness.org/talk/viewthread.php?tid=6372&a...

Bangladesh has a greater population at 158 million than Russia with 142 million.
in a country just 1/118 the size , 144000 sq km to Russia's 17 million sq km.
an area smaller than the state of Iowa. Yet the fertility of the Ganges delta assures
agricultural bounty. By example Bangladesh shows that scenarios of overpopulation
bringing biblical ruin to world civilization is all fanciful imagery. In the parlance of
environmentalists it is ' sustainable '.

http://www.youtube.com/watch?v=QwfH1gYkXTw
http://www.census.gov/newsroom/releases/img/babyboomers_pyra...
http://www.youtube.com/watch?v=XNxAzHSprug&t=28m56s
http://www.youtube.com/watch?v=L8XQjfG2wYc


A side note : The central premise of anthropomorphic climate change is that people are the cause.
Assuming for argument that this could be true , it will never happen because the people are not
going to be here to make it happen.

crazyboy - 4-8-2015 at 14:05

franklyn, I think the argument that overpopulation is a nonissue because India has over 1 billion people and can feed itself is spurious. India is a developing nation and many of its inhabitants live in extreme poverty, as India becomes richer it will consume vastly more resources including electricity, petroleum, water, and consumer goods. As nations develop they inevitably consume more fish, meat, and milk all of require more water and energy to produce than the equivalent calories in plants. The US comprises 5% of the global population but consumes 24% of global energy, imagine the resources needed such that the rest of the world could enjoy the energy consumption of the US.

That said I'm not a population freak, I believe most projected estimates have global population stabilizing around 9 billion in 2050 as fertility rates continue to trend downward as nations develop. While I'm not particularly concerned about our ability to feed ourselves I do think that climate change is a serious issue that will likely remain largely unresolved. When the ozone was being destroyed it was relatively easy to curb the use of CFCs, the same is not true of carbon emissions. I suspect any cuts to global carbon emissions will be largely symbolic and by the time nations are seriously ready to address climate change it will be too late in some respects.

Back to the topic at hand though, one reason I am optimistic about the potential of phage therapy despite it's lack of attention in the west is the increasingly lower cost of DNA sequencing and synthesis. In the near future these technologies will be significantly affordable such that pathogenic bacteria presenting in infections can be rapidly sequenced and a DNA or RNA sequence for a phage which attacks that species or strain of bacteria could be synthesized on site. JCVI is working on such a technology for rapid vaccine development which could be applicable: http://www.jcvi.org/cms/press/press-releases/full-text/artic...

This could be used to build libraries of phages, and new phages would be produced when a new strain emerges. Although bacteria would evolve resistance the ubiquity of phages in the natural world indicates that an evolutionary arms race is sustainable and possibly winnable.

ziqquratu - 4-8-2015 at 16:24

Quote: Originally posted by franklyn  
The alternative , Phages are natually occuring agents and so do not require the same testing as drugs.
Since western medicine is wedded to pharmaceutical usage this treatment is uninvestigated.
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Morphine is a naturally occurring agent, and yet it seems to make drug manufacturers a significant amount of money. Last I checked, aspirin continues to sell rather well. Just about all of the traditional antibiotics - and many of the modern ones - are entirely derived from natural sources (usually by fermentation using appropriate yeasts/fungi). And you can get your lovastatin from red yeast rice or from Merck - the choice largely depends on how you feel about quality control.

Last I heard, around half of all drugs currently on the market are either natural products or directly derived from natural products. And these drugs can all be patented and profitable - even without patents they can be very profitable (morphine!).

Likewise, many phage therapies would be readily patentable, and would be evaluated and regulated just like any other pharmaceutical. One of the major problems facing phage therapy, as far as evaluating safety and efficacy, is that consistency between batches is very difficult to achieve - due to the high mutation rate, what goes in to a production vessel (or a patient!) is likely to be quite different to what comes out! This might require regulatory agencies to consider them slightly differently to a traditional small molecule drug, but that process is already becoming more common due to the emergence of so-called "biologics" which have related difficulties.

In contrast to your claims, phage therapy has been very broadly investigated. The review article you provided from 2001 (14 years ago!) gives a mere 78 references (although it clearly states that it's not trying to be comprehensive). In contrast, a quick PubMed search for "phage therapy" returns nearly 18,000 hits! Hardly what I'd call "uninvestigated". If you read the article you provided, you'll see that it actually discusses why phage therapy isn't in widespread use - primarily lack of reliable data, poor efficacy and difficulties in preparation and administration.

I note the nature article you provided talks about problems with patentability of phage therapy, which, if true, would support your "no profit" argument. Of course, if we observe that:

we might conclude that patentability isn't too much of a problem.


To population - I recall hearing about a (recent?) "analysis" which claimed that the entire 7 billion people on the planet could comfortably fit into Texas (with space equivalent to a typical New York apartment or something). That might well be true. But it's not all about living space. We each use a LOT of land, much of which we will never set foot on. We need land to grow food (and, coincidentally, we tend to like to live in the areas which would be optimal for food growth, since the climate is so nice, there's plenty of water and just the right amount of sun, which means food production often takes place in less optimal locations). Oh, and don't forget about water! We need a lot of that, and it needs to be stored somewhere in between "delivery" and use! And, of course, we need space to park our cars, moor our yachts, hunt with our weapons, school our children, warehouse goods prior to sale - heck, to house our home chemistry labs! And we also have to leave a little space for the other species on the planet...

Aside from food production, however, we also need resources - all of which are, to one degree or another, limited. Plants tend to like a bit of soluble nitrogen and phosphorous in their diet, which is depleted when the plants are removed so that we can turn them into food (and our efforts to recover trace nutrients from waste streams are woeful - it's cheaper to produce more ammonia or mine more phosphates and ship them in). We require half the periodic table just to get our computers running so that we can have these discussions - and many of those elements are difficult to come by. We need lots of energy - and thus lots of coal, oil, gas, uranium and, indeed, space to house power plants, mines, solar arrays and wind farms!

Please, at least be better than to equate "overpopulation" with "running out of space." I doubt that anyone who makes claims about overpopulation really thinks that "space" is the problem.