Using Old Medications to Defeat Tuberculosis 70
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."
Links to actual papers for more info ... (Score:5, Informative)
Can't say I understand this stuff, but for those who do, these probably should have been in the story snippet.
beta-lactamase inhibitor (Score:5, Informative)
http://en.wikipedia.org/wiki/Clavulanate
Re:Links to actual papers for more info ... (Score:5, Informative)
Re:Links to actual papers for more info ... (Score:4, Informative)
Amoxicillin-Potassium Clavulanate Combination (Score:4, Informative)
This article seems to be missing something... (Score:3, Informative)
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.
Re:In other news... (Score:2, Informative)
Interesting, but no guarantees here. (Score:4, Informative)
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.