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Using Old Medications to Defeat Tuberculosis
TastesLikeCoughSyrup writes "Antibiotic resistant tuberculosis is spreading like wildfire in the developing world. While many researchers are looking for new drugs to combat the disease, those efforts could take years to bear fruit. Meanwhile, two scientists at the Albert Einstein College of Medicine have learned how the drug clavulanate can destroy the defenses of tuberculosis, making it vulnerable to medications in the penicillin family. The best part: it has already been approved by the FDA so doctors can start using it immediately."
Research page at Blanchard Lab (part of the AE college of medicine) and the ACS paper about their research.
Can't say I understand this stuff, but for those who do, these probably should have been in the story snippet.
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those efforts could take years to bear fruit.
I don't think fruit is going to help against tuberculosis.
The theory of relativity doesn't work right in Arkansas.
It's a beta-lactamase inhibitor, it stops beta-lactamase from cleaving the 4 atom ring of penicillin-like drugs. This ring is very important in the function of Penicillin which actually prevents the building of cell walls in gram-positive bacteria. these bacteria need a thick cell wall to keep from bursting. this drug in of its self does little, only combined with penicillins does it revive the drug's germ killing power.
http://en.wikipedia.org/wiki/Clavulanate
Sigs are too short to say anything truly profound so read the above post instead.
You'll see. You'll all see.
Those of us allergic to penicillin will simply evolve and grow gills. So while you all cling to your antibiotics and inhibitors on the poisoned land, me and my brothers and sisters will be ruling the sea!
Each of us were required to have chest X-Rays. My understanding is that if they showed that either of us had tuberculosis, our visas would be denied.
However, the doctor who gave me my medical exam - which was rather thorough - told me that I should show my passport to the X-Ray technician, just to make sure someone else wasn't able to stand in for me. I offered it to her, but she didn't bother with it.
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Interactive Visual Medical Dictionary
One thing I have done is made Manuka honey mead, which is interesting as it means that either I destroyed the antibacterial agent when using heat to dissolve the honey, or the agent has no significant ability to slow yeast cultures.
It's a small world and it smells funny; I'd buy another if it wasn't for the money; Take back what I paid (SoM)
Having spent the last couple years living in a developing country where TB is endemic/epidemic (Tanzania), I am usually pretty jaded when it comes to things like this- malaria and TB being "forgotten" by the rich world and all that jazz.
However, I take encouragement from two things about this:
First is that it's an older drug, which means it will probably be off-patent soon (anyone know?). This should guarantee it's fairly affordable. Also, it's a proven drug with a clean track record so far. Both of those mean that governments like Tanzania are more likely to implement it's use for TB.
Second is that it may (and I'm speculating here) shorten the treatment time for TB. That could be big. Current treatment time is on the order of months, if the drugs are more effective then it follows that the treatment might be shorter. That would be good for compliance: In the rich world it's hard to get people to take pills regularly for months on end, and it's no different anywhere else. People forget, or they feel better and don't think they have to continue, it happens.
Tanzania has a TB control program which provides free medicine and Tanzanians can take medicine just as well as the rest of us. Sadly, rural clinics often don't have enough drugs to give out a whole course of treatment to everyone, so people have to return for more pills, and again for check-ups. That often means a large disruption in daily life (imagine walking an entire day to get to a clinic, then going back), and the decisions presented are not easy: skipping work regularly to go get your medicine/checkup could impact your crop, your herd, get you fired etc. I wonder how many cases of TB have relapsed or spread due to this sort of coerced non-compliance? Less disruption is a win on all fronts.
On a less serious note, I am reminded of a particularly bad cross-country trip where I was crammed in the back of a ricketty Land Rover 110 with at least 12 people (just in the back compartment, I think the total headcount was over 20, not counting chickens). I was directly across a man who was a textbook case of kifua kikuu (TB), and the ride was almost 12 hours, with breakdowns. At a certain point, I just resigned myself to catching it.
Amazingly, I didn't. I didn't get malaria once either.
But in the end, malaria, TB and HIV were about the only things I didn't get at some point.
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The FA mentions use of clavulanate, if you read the abstract for the ACS article linked to by the FA you will see there are three beta lactamase inhibitors - sulbactam, tazobactam, and clavulanate - trialled.
Apparently nobody really has tried beta-lactam antibiotics in this indication, but it seems suprising that any medical professional would consider this a "one-two punch strategy". Realistically this would be one combo of a multi hit process. Modern day TB therapy always includes a specifically chosen 3-4 drug combination. This combination depends on where the infection was contracted along with any characterisation of the strain that is possible. This is simply because if you feed a drug that's not killing it, you're selecting for resistance to that drug. If physicians start using beta-lactamase inhibitors they'd better be careful because there are already several examples of other infections resistant to clavulanic acid (just google search).
Whilst the article reports this as if it is a major breakthrough, this is purely sensationalism. It is a minor breakthrough in a major problem.
It's an interesting study, and they're doing it right, but there's no particular breakthrough yet. This is an in vitro study with no clinical implications yet. TB is a significant problem where I work (I'm a doctor in the Western US), but there are some hurdles to get over before I can start using clavulanate.
Clinical utility is the Holy Grail here - the biochemical activity of a drug is critical, but the effect of the drug on the infection in an infected person is a lot more complicated. You have to get an effective concentration of the antibiotic into the area of the organism, get the bug to take up appropriate quantities of it, and not injure the patient in the process. Every step of this can kill an otherwise promising use of the drug.
In the case of clavulanate, we know that it causes significant side effects. I use it a LOT in kids (Augmentin is your friend for a variety of conditions, and clavulanate is what makes Augmentin Augmentin), and it causes pretty impressive diarrhea at fairly low doses. Diarrhea, especially if it involves altered intestinal flora, is a set-up for C. difficile colitis, which can be deadly. If we need high concentrations of clavulanate, we may not be able to give enough of it to patients. Or there may be other toxicities, although it's been quite benign in widespread use to date.
Another problem is that the bacterium can mutate proteins to avoid drugs, and TB is pretty good at this. MDR TB didn't happen by accident, and mutation of beta-lactamases to avoid clavulanate is not unheard of. Overproduction of the enzyme is also possible, and would then increase the required dose of the drug (and see above).
A final problem is the physical defenses of the bug. The cell wall for TB is quite effective and strong, and the bacterium has a variety of transport mechanisms to get antibiotics out of the cell. Again, we may not be able to get enough clavulanate into the cell long enough to kill it.
Having said all of that, I'm delighted both that the work is being done and that these initial results are promising. It will be fun to see what happens clinically.