 Here, everybody, Dr. O. This video we're going to talk about the polymixin antibiotics. I think this is a very important video. I'd like to think that I don't make a video that isn't important. It's the stuff that I want you to learn. But polymixin, you're going to see why in just a little bit, it's super, super important. So let's start by just talking about how they work. So I'll just read through here. It interacts with the lipopolysaccharide in the outer membrane of gram-negative bacteria, killing the cells through eventual disruption of the outer membrane and cytoplasmic membrane. We see there is the outer membrane, meaning these drugs are going to be very important for gram-negative bacteria. And the reason that's important is because most of the drug-resistant strains were concerned about are gram-negative. At this point, about 95% of research funding is going towards dealing with gram-negative bacteria. And I covered that in the cell wall video, the cell, you know, the gram-negative versus gram-positive video. The reasons why gram-negatives are generally more dangerous, right? Some drugs can't get inside of them. Some can be pumped out of them in ways they can't against gram-positives, etc., etc. So they are the scariest of the organisms. There are some gram-positives out there that do tons of damage. But if you can create an antibiotic that can impact these drug-resistant gram-negatives, that's going to have the potential to really help us as a species. So let's just talk about polymix and B first. So they were first discovered in the 40s, lack lots of them. Isn't it crazy to think how many antibiotics were discovered way back then? Or not seeing them discovered at the same rate? I always like to say that the low-hanging fruits are already been picked. There hasn't been like new classes of antibiotics in a long time. So we need to do something. We need to come up with something to stay one step ahead of these microbes. So they were discovered in 1947. So it would have been basillus, basillus polymixin. So polymixin B and polymixin E, which you'll hear called colistin way more often, are the two that we're going to talk about. So polymixin B, the problem is these antibiotics disrupt cell membranes. So we want them to destroy the outer membrane of gram-negative bacteria, but like it says, there can also impact the cytoplasmic membrane, the cell membrane or plasma membrane, which we have. So this is not an example of a selectively toxic drug, because it can impact our cell membranes. So polymixin B and polymixin E, they both can affect the cell membranes of kidney cells. They're not toxic, but also the nervous system. But that's why polymixin B is really only used topically in triple antibiotic or other preparations. So triple antibiotic, you've got neosporin, which would have neomycin, bacitracin, and now polymixin B. So those are going to be the three antibiotics that make up your neosporin or triple antibiotic. When is this especially effective? It is still, you know, polymixin antibiotics are still very effective against pseudomonas. Let's go ahead and move on and talk about colistin or polymixin E. There's a little bit of a history lesson here as well. So the polymixin antibiotics have been around for a long time. At one point, colistin was being used, but they realized that it was especially nephrotoxic. It was damaged into the kidneys, so they quit using colistin, except for some limited uses. So it's absorbed poorly. It causes kidney damage. So primarily, I'll read here when it was primarily being used, oral dosing to decontaminate the bowels to prevent infection in immunocompromised patients or patients undergoing invasive surgery slash procedures. So what that means is, since it isn't absorbed very well and can kill the gram-negative bacteria living in the gut, they would use it just to massively bring down the population of gram-negative bacteria in the gut. That's what a bowel decontamination is if there was concerns of these organisms causing an infection, killing a patient, getting into the body. So that was primarily what it was being used for, but it really wasn't being used much clinically. So since it wasn't being used clinically and for very limited uses, it started to be used agriculturally. So colistin has been used especially in pork production, so like in pig farms in China, they've used thousands of pounds of this antibiotic. And then it wasn't being used for humans, so it had this agricultural use. Well, in 2015 is when they first found signs of colistin-resistant organisms on these pig farms in China primarily. Rather than because the world has shrunk down because of travel and food and people moving and bringing organisms with them and the rapid evolution of these organisms. By 2017, we're already seeing relatively serious problems or at least an increase in colistin-resistant organisms in patients in the United States. So think about how quickly things can evolve and change from not being a problem, to resistance on pig farms in China, to resistance in humans in America in just a couple of years. In 2016, there was a handful of cases, but they all lived in, they were all compromised people living in long-term care facilities, but now you're talking about relatively healthy people. So this is a problem, and the reason this is a problem I've talked about in a different video is if the CRE organisms, the carbapenem-resistant anterior bacteria C, which can already resist all of the beta-lactam antibiotics, if they also become colistin-resistant, we will have Pseudomonas, Klebselonamonia, Shigella, E. coli. We will have members of this family of bacteria that we don't have treatments for, like truly untreatable bacteria with our current antibiotics. So I'm hoping that we'll come up with alternatives, a big fan of phage therapy, maybe quorum-sensing inhibitors, whatever it might be. That's why I wanted to talk about this history part of it because it's been around a long time, but you're seeing the rapid resistance now because it's agricultural uses, but then it is being used and has been used for a while. So the main reason colistin is important is right now it is the last line of defense against these CREs, which are superbug infections, meaning they're multi-drug resistant. So let's talk about the intravenous uses then. So oral was just for valedict contamination because it isn't absorbed well through the gut anyway. Intravenous dosing to treat serious systemic infections, primarily these CRE drug-resistant superbugs, caused by multi-drug-resistant pathogens. So it's been used in that way since the 90s, but it was just used a little bit and now you're seeing it used more and more. It was primarily used when they first started to reuse this or reintroduce this into treating humans. It was used with children with cystic fibrosis that had pseudomonas infections. So I mentioned in other videos why pseudomonas is a big problem with CF patients. But we're now relying on this drug to be our last line of defense against these CRE organisms, carbapenem-resistant anterior bacteriose. They are some of these, like if you have a CRE infection with treatment, half the people in the blood, if the infection gets to the blood half the people are still going to die. So we are running out of antibiotics to fight this group. That's why if you went to Google right now and typed in nightmare bug, nightmare bacteria, chances are you're going to see one of the CREs. All right. So these are your polymixin antibiotics, polymixin B is just used topically in the triple antibiotic ointments and it's good against CREs, just like polymixin E is. But this one, this is the antibiotic out of all of them that I'm paying the most attention to because if this antibiotic stops working, we are in a much more serious situation than we already are now, which we already have tens of thousands of people dying from drug-resistant infections. So I definitely don't want to see this get any worse. I hope this helps. Good luck sleeping tonight. Have a wonderful day. Be blessed.