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W; I’m Kelly Klein and today I’m speaking with David Grimm, online news editor for Science, about some of the recent stories from our online daily news site. So Dave, you are going to talk with me about "how not to treat a disease", are you?
M: Right, Kelly. Well, this study is a little bit counter-intuitive because it suggests that taking two drugs at once may actually be worse for treating the disease than better. This approach, especially taking two antibiotics at once, is called synergistic therapy. And what researchers thought the advantage was that, you know, different drugs attack different parts of an invading microorganism, like a bacterium.
W: Just as we have heard that doctors use these drug combinations in everything from treating HIV to MRSA, which is a very highly resistant pathogen that’s often acquired in hospitals.
M:(l)But this new study suggests that maybe two drugs at once isn’t such a good idea.
W: Right, because as soon as we start talking about antibiotics we have to start thinking about bacterial resistance.
M: Exactly, and that seems to be what happens here. What happens when bacteria evolve resistance is that they find some way to overcome, or members of their population find a way to overcome the drug, and when the drug kills all the other bacteria off, you’ve got these few bacteria that are left that are resistant, and they are able to multiply. And all of a sudden your drug doesn’t work anymore.
W: That explains the appearance of resistance. Then, what will happen if we use two antibiotics together?
M: Well, it turns out that seems to be happening even more dramatically when you use two antibiotics at once, or at least that’s what these researchers have shown. What they did was they took E.coli, which can be a pretty nasty pathogen, and they treated it with two common antibiotics: doxycycline and erythromycin.(2)They basically put these E. coli in a test tube. They added both drugs, and after a day, the drugs seemed to almost completely wipe out the E.coli, which is sort of expected.
W: It doesn’t sound too bad, so far.
M: What was shocking was the following day the E. coli experienced this population explosion. All of a sudden their numbers were up to 500% higher than they had been before. So they just really started multiplying, really out of control. And at first the researchers thought they had made some sort of mistake. They repeated the experiment, and they saw the same thing happen again.
W: That’s really unexpected. So I assume this new population is much more likely to be resistant to the antibiotics that were used.
M: It is. And what the researchers found was that, just like what happens with one drug, with a couple drugs it still left a few bacteria left in this population that were really good at fighting these antibiotics. In fact the bacteria seemed to have multiple genes for pumping out these antibiotics.(3)So these antibiotics, you know, get into the bacterial cell and the bacterium usually dies, but there are some bacteria that were very good at just basically pumping this antibiotic right back out again. And those were the ones that survived. And even in the presence of two antibiotics they just started to thrive after about a day because the antibiotics had wiped out all their competition. So all of a sudden they had access to all these resources, all this food that they didn’t have access to before. And that they’re basically growing out of control because the drugs aren’t having any effect on them.
W: And so the two examples of really nasty diseases that you mentioned earlier, both HIV and MRSA, in which this synergistic method is used quite a bit. I mean they’re really difficult-to-treat diseases. If we start not using this method, are there any alternative methods for treating them?
M: Well,(4)one thing the researchers suggest is instead of hitting bacteria with two drugs at the same time we should alternate the drugs. So use one drug one day, wipe out most of the population, and maybe you’ll have some leftovers that are resistant to that drug, but then you hit it with a different drug the next day, and maybe that will wipe out the remainder.
W: I get it. This idea is sort of mix things up so much that bacteria really don’t have a chance to become resistant. That’s certainly one possible way to go.
M:(5)All this stuff is in test tubes right now, so it sort of remains to be seen whether this is actually happening in the human body. But it is a really powerful warning sign for a lot of these multi-drug treatments.
W: Indeed. Well, thank you, Dave, for sharing with us such interesting information.
M: My pleasure.