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Author: Subject: Bacterial resistance to antibiotics.
Vogelzang
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[*] posted on 14-9-2012 at 13:04


OPP and TB

http://naldc.nal.usda.gov/download/IND43968019/PDF
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Morgan
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[*] posted on 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
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zed
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[*] posted on 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.



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[*] posted on 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.




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watson.fawkes
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[*] posted on 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.
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[*] posted on 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





Knowledge is useless to useless people...

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Vogelzang
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[*] posted on 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]
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Vogelzang
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[*] posted on 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...
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White Yeti
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[*] posted on 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...




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[*] posted on 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.
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Oscilllator
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[*] posted on 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.




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Vogelzang
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[*] posted on 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]
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AJKOER
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[*] posted on 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.
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[*] posted on 31-10-2014 at 17:41


perhaps here some info :)

http://g2cforum.org/index.php/list/other-alternatives/28556-...
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Chemosynthesis
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[*] posted on 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/
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[*] posted on 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.
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[*] posted on 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.
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[*] posted on 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.




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Chemosynthesis
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[*] posted on 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.
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[*] posted on 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.
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Chemosynthesis
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[*] posted on 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]
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macckone
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[*] posted on 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?
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[*] posted on 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.
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[*] posted on 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.
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[*] posted on 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.
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