hey carob a doctor oh this video were going to talk about the polymyxin antibiotics I think this is a very important video and I'd like to think that I don't make a video that isn't important it's stuff that I want you to learn but polymyxin 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 your interacts with the Lippa polysaccharide in the outer membrane of gram-negative bacteria killing the cells through eventual disruption of the outer membrane and cytoplasmic membrane so the key there is the outer membrane mean 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 a gram-negative at this point about 95 percent 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 you can 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're 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 that can impact these drug-resistant gram negatives that that's gonna have the potential to really help us as a species but let's just talk about polymyxin B first so ever they were first discovered in the in the 40s like lots of them isn't it crazy to think how many antibiotics were discovered way back then we're not seeing them discovered at the same rate I always like to say that the the low-hanging fruits already been picked it's pika 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 at one step ahead of these microbes so they were discovered in 1947 so it would have been bacillus bacillus pollen poly mix-up so probably polymyxin B and polymyxin II which you'll hear called coalesced and way more often are the two that we're going to talk about so polymyxin B the problem is like these these antibiotics disrupt some membranes so the big that 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 right so this is not an example of a selectively toxic drug because it can it can impact our our cell membranes so polymyxin B and polymyxin e they both can they both can affect the cell membranes of kidney cells so their nephrotoxic but also the nervous system but that's why polymyxin B is really only used topically in triple antibiotic or other other preparations so triple antibiotic you've got neosporin which would have neomycin bacitracin and now polymyxin B so those are gonna be the three antibiotics that make up your neosporin or triple antibiotic when is this especially effective it is still you know polymyxin antibiotics are still very effective against Pseudomonas but let's go ahead and move on and talk and talk about colas dinner probably mix an e go through a little bit of a history lesson here as well so the polymyxin antibiotics have been around for a long time at one point a cola stand was being used but they realized that it was especially nephrotoxic it was damaging to the kidneys so they quit using Cola stem except for some limited uses so it's a it's absorbed poorly it causes kidney damage so primarily I'll read here when it was primarily being used oral dosing to decant 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 absorb very well and can kill the ground 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 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 that it started to be used agriculturally so coalesced in has has been used especially in pork production so I can pick pig farms in China they've used thousands of pounds of this antibiotic and then it so there wasn't it wasn't being used for humans so they had this agricultural useful in 2015 is when they first found signs of coalesced and resistant organisms on these pig farms in China primarily but then you know because the world is 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 Cola storm 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 you know they were all immunocompromised people living in long-term care facilities and but now you're talking about relatively healthy people so this so this is this is a problem and the reason this is the problem I've talked about in a different video is if the CRE organisms the carbapenem resistant anterior bacteria see which can already resist all of the beta-lactam antibiotics if they also become coalesced and resistant then we will have Pseudomonas climb cell and pneumonia Shigella ecoli we will have members of this family of bacteria that we don't have treatments for like truly untreatable bacteria with our 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 so that's why I wanted to talk about this history part of it cuz it's been around a long time but you're seeing the rapid resistance now because it because it's its agricultural uses but then it is it is being used and has been used for a while so the main reason Coulson is important though is right now it is the last line of defense against these CR es which are superbug infections meaning they're multi drug-resistant so let's talk about the intravenous uses then so oral was just for bowel decontamination 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 that'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 into treating humans it was used with children that had with cystic fibrosis that had Pseudomonas infections so I mentioned other videos why Pseudomonas is a big problem with CF patients but we're now we're now relying on this drug to be our last line defense against the CRE organisms carbapenem resistant anterior bacteria see they are you know 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 to fight this this group that's why if you went to Google right now and typed in nightmare bug nightmare bacteria chances are you're gonna see one of the CRTs all right so these are your polymyxin antibiotics polymyxin bees just used topically in the triple antibiotic ointments and it's good against cooking Pseudomonas just like polly mix and he is but this one this 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 sleep in the night have a wonderful day be blessed