A few months ago the major public presses were going wild with a rise in MRSA infections. For those who don't remember, MRSA, methicillin-resistant staphylococcus aureus, is an infection which is resistant to most forms of treatment. There are several strains which have been isolated which are resistant to virtually all known forms of treatment. Essentially if are infected with MRSA, which usually happens in communal settings (mainly a hospital), chances are the docs may have a hell of a time getting rid of it.
It is a very serious problem which will only becoming worse over the coming years. Over prescribing of antibiotics and generally lack of understanding of bacteria has effectively left only the strongest of the strains remaining. Most of these are gram negative bacteria, which are even harder to fight due to their double membranes.
In recent years the mechanism behind resistance in bacteria has begun to be understood. There are several factors regarding it, the permeability of the outer membrane, side chains of the antibiotics, polarity, etc, but the big bad boy have been the efflux pumps. Efflux pumps remove antibiotics from the cell once they finally make their way in. Think of them like a bilge pump on a ship. Except that these pumps, in the most resistant strains, move EVERYTHING out. It's like the mother of all shop vacs in a cell. And it's a huge pain in the ass when trying to kill it.
There are several options on how to combat this, none of which are viable at the moment. You can increase the permeability of the bacteria (basically let the antibiotics in faster than they can be pumped out), bind a substrate to the pump (pretty much put a plug in it) and the last option is to alter what the pumps push out. While reading through all these studies, most of which read like a thick ass pound cake, I came across a treatment in the later option that was rather intriguing. They have found that Verapmil and Reserpine inhibit the pumps and allow antibiotic concentrations to rise.
Think about that now. How long have those drugs existed? How many people the world over have been on such a regiment? That's pretty damn cool if you ask me, that something which has been used for years and years has yet another viable function.
They will never be used in humans as a treatment as the levels needed to inhibit the pumps are highly neurotoxic. There is also issues with purification of the needed amounts of the compounds. What they are doing instead is using those two drugs as a start point to construct new, less toxic variations to inhibit pump function. It is one of the most promising fields of micro and molecular biology at the moment.
Stumbled across this while writing a paper on antibiotic resistance in bacteria for my microbiology class. Was a vastly interesting tidbit that I thought all the other pharmacy nerds would enjoy.
Now back to my macroeconomics paper on universal health care :D
4 comments:
As a 3rd year pharmacy student who doesn't know enough about this stuff yet, but who has been furiously studying antibiotics for my therapeutics exam, I had to ask something.
I was under the impression that MRSA/VRSA are resistant due to PBP mutation. Are the efflux pumps mostly relevant to future resistance in eg. linezolid?
I could totally be missing something here...
From what I have gathered, and mind you I'm only an undergrad and have studied this on my own, bacteria are suseptiable to most types of antibiotics. What makes them resistant to certain ones is the combination of porins and efflux pumps and how high the concentrations become.
There is nothing overly special about MRSA other than the fact it has MDR pumps which constantly pump out the antibiotics as they move in. I did not look at MRSA specifically, but came across several articles that stated that MRSA was exceptionally resistant to the influx of antibiotics.
Whether or not those antibiotics would actually destroy the bacteria I do not know. To be honest I don't remember of the top of my head which course is better (death by protein dehydrogenation, peptidoglycan inhibition, etc). I wanted to go more indepth by my other papers were calling to me instead.
If you are interested in it I can send you my paper with the sources in it. All of the papers are public, so you could flip through them if you wished.
Thanks for the compliment over on TAP ;)
I've checked out your blog before. I liked the Diltiazem capsules = penis post. And Cyanide and Happiness is my favorite daily distraction.
One area often overlooked in the battle against the transfer of dangerous infectious diseases like MRSA in medical environments are the ubiquitous keyboards and mice. Standard keyboards and mice can not be disinfected because germs collect around and in seams and under keys. Recently Man & Machine, Inc. released a White Paper titled, “Minimizing Transmission of Infectious Disease in Heath Care Environments by Use of Disinfectable PC Keyboards and Mice.” It can be viewed at: http://www.man-machine.com/whitepaper.htm
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