DIP Episode 27 - Antibiotics Part 1 (Cell Wall Inhibitors)

Okay, welcome. My name is Divine. I am a fourth-year medical student. Welcome to the 27th episode of the Divine Intervention Podcasts. Today I'm going to be talking about something very high-yield and something that I guess a lot of people have requested, which is micro from our college. This will obviously be in sections because we can do everything all at once. But today I'm basically going to talk about all the penicillin, the sephalus, and all that fun stuff. So basically all the penicillin like antibiotics I will discuss in this podcast. And I will definitely make sure you know this as your preprint for step one. Don't walk into the exam room where you can step one without knowing your antibiotics. You just be setting yourself up for things that are not necessarily good. Okay, so let's begin. So I think it's pertinent to discuss a few principles relating to farm before jumping right into the penicillins. The first principle I will talk about is distinguishing between bacterial cytol and bacterial static drugs. So, bacterial cytol drugs, they kill bacteria. They are much better for people that are immunocompromised. But on the other hand, bacterial static drugs, they prevent bacterial growth. So the bacteria will probably still be alive, but it doesn't grow as much. These are better for people that have good immune systems that can fight off the bug, as long as the infection is not a region infection.

And if you're thinking about your pertin synthesis inhibitors, remember that you are immunoglycosides, a bacterial cytol. Actually all your penicillins are actually bacterial cytol as well. Okay, but starting from your tetracycline, you begin to jump into the purview of a bacterial static agent. Another principle is the principle of comparing the minimum inhibitory concentration to the minimum bacterial cytol concentration. So the minimum inhibitory concentration, basically, or your MIC, just think of it as the amount of drug you need to give, so that 99% of organisms will not grow. Okay, it's more of a bacterial static drug concept. Contrast that with a minimum bacterial cytol concentration, right? Where you basically determine the amount of drug you need to give to kill 99% of organisms. Obviously, this will not be a bacterial static drug concept. It'll be a bacterial cytol drug concept. And then one of the things you should probably realize, I think you'll sort of give you like framework for thinking about certain side effects. You get with these antibiotics, is many of these antibiotics, you get them from like other bugs, like from other bacteria, from other fungi. So those things are obviously foreign to us. That's why we can get hypersensitivity reactions with many of these antibiotics. So the first group I will talk about are the cell wall inhibitors, basically your penicillinants. Don't forget the constituents of the cell wall, right?

The differences between gram positives and gram negatives, right? So gram negatives remember they do have an outer membrane, right? And in addition, they have like, they have a pore-ins, which help to basically bring stuff across the membrane. And remember that this outer membrane is actually the thing that contains lipopolisaccharide, right? That's endotoxin, which when is exposed to your bloodstream or whatever causes all this nasty havoc, okay? And don't forget your gram negatives also have the periplasmic space, right? It's basically a space between the outer membrane and the inner cell wall, right? That's where your beta-lactamine sort of hangs out. Beta-lactamine hangs out in that periplasmic space. You'll talk about beta-lactamine in a bit. So there'll be the side of action, right? So you can get a gram positive or gram, I mean a gram-negative diagram, I guess, where they show you the talk about a drug and accuse them like clavolanic acid, for example. And as for the side of action, you want to be able to match that to the periplasmic space, because that's where beta-lactamine hangs out. Now, gram positives, right? They have a cell wall. Bicoplasma does not have a cell wall, right? It's kind of unique. Remember, one of those causes, it's probably the more micoplasma pneumonia, it's probably one of the most common causes. And it's actually how you ought to know that. Most common causes are for atypical pneumonia, right? So like more indolent course kind of pneumonia.

That's why for mycoplasma, right? That's why you need, because they don't have a cell wall, right? You use a protein synthesis inhibitor, like a macrolyb to treat those kinds of infections. Now, another thing I want to talk about, right? So I'm not just going to just real off facts for you to memorize. No, I'm not adding much value there. I'm going to try to give you principles. Once you know the principles, it's much easier to cement the drug names on those principles as a foundation. So the first thing we'll talk about is transpeptidase, right? So transpeptidase, I sort of think of it as something that marries two people. Okay? The thing it does is it basically waits to alanine subunits together. It sort of makes them cross linked so you can form the cell wall. Okay? So the thing is transpeptidase. Think of it as an example of a penicillin binding protein, because penicillin binds to it and exerts its actions that way. So penicillin, it binds transpeptidase. Okay? And the thing is penicillin actually looks a lot like alanine, right? So that's why transpeptidase is like, ooh, look at this cool alanine hanging out around here, but it doesn't know it's penicillin. That's basically how penicillin works. Okay? So when transpeptidase picks up penicillin, you don't have cross-linking of those alanine residues, so you don't have the synthesis of the bacterial cell wall. Okay? And basically the bacterial cell dies. Okay?

And this is essentially the mechanism of action of all penicillins, all the cephalosporins, all the carbopenemps, even astringent. They all work this way. Okay? And one thing I'll just mention here, because this occasionally creeps its wing to end being the exams, is the auto-licens, the auto-licens, they actually enzymes that routinely break down the cell wall of bacteria. Okay? So the thing is, in general, you have sort of like an equilibrium where you're constantly making bacterial cell walls with transpeptidase, and you're constantly breaking down bacterial cell walls with auto-licens. But if in hippy transpeptidase, the auto-licens are working on a post, okay? So the cell will have like a net breakdown, and the cell will explode and die. And when these cells explode and die, they spill the bacteria products into the circulation, you can actually have a pretty powerful immune response to this, right? So that's the mechanism behind the gyroshachymer reaction with penicillins. Now, so we've talked about one way to kill bugs by attacking transpeptidase. But think about it. We know that transpeptidase binds to alanine residues, right? So if we could modify that alanine in some way or make it impossible for transpeptidase to recognize that alanine, who also caused the breakdown of the bacterial cell wall, okay? So that is how vancomycin works, right?

So vancomycin binds to that alanine residue that you find on the things you're cross-linked to from the bacterial cell wall, and then transpeptidase cannot find the alanine anymore, okay? And that's how vancomycin works as an anti-microbial agent, okay? And if you think about it, if you change that alanine residue, right? So from the alanine to the alanine to lactate, then you basically get vancomycin resistance because vancomycin cannot bind lactate. Now, another thing you could do, right? So I guess I'm very willing to resistance mode here. But think about it if you change the structure of transpeptidase by some means, right? Penicillin will not be able to recognize it, right? That's actually the mechanism of resistance to methecylene, right? You basically alter the transpeptidase structure, and that's how you get methecylene resistance, right? So that's where you go from MSSA to MRSA. And the thing is, there are certain enzymes, right? They're called beta-lactamesis. They can cleave the amide rings. You find them beta-lactams, okay? And basically, if you chop up these beta-lactam antibiotics, if you destroy that amide ring, you lose the functionality. So the thing is, in general, beta-lactamesis actually not expressed natively by bacteria for the most part, not always troubled for the most part. Most of them actually come from plasmids, okay? Basically from bacteria-fage genes, okay? So that's how you get resistance to penicillin in certain box.

So one thing I probably want to call your attention to here, because they would love to sort of mess with your head with this on exams, right? So think about it. If this is a phage-mediated mechanism of resistance, right? It's different from the mechanism of resistance, where you change the structure of transpeptidase, like I described in going from MSSA to MRSA. When you alter the structure of transpeptidase transpeptidase, it's something that is routinely encoded by bacteria, okay? So that'll be a chromosomal, I guess, chromosomally-mediated mechanism of resistance, okay? That's what you get with methecylin resistance. Contrast that with the beta-lactamesis business, where it's more of phage-plasmid-mediated mechanism of resistance, okay? And the good thing here is we do have certain drugs that can inhibit beta-lactamesis. We have like clavolanica, say we usually add that to our moxicillin. It augments the activity of augmenting. Remember, augmenting is a moxicillin and clavolanica acid. Another one is so backtam, right? So backtam usually add that to peneanpecellin. And then tizobactam, right, is the thing that is the second constituent of vitamin Z, or zoosin, right? So peep-tase, if you ever heard that in the hospital, tizobactam is usually added to paparacillin. Paparacillin is one of the antisodomono penecellins I'll talk about in a few minutes. So again, these drugs they present themselves to beta-lactamesis.

So once beta-lactamesis does something to them, beta-lactamesis doesn't work anymore, okay? So now we've talked about these principles. Now let's jump into the actual drugs, okay? So the first one we'll talk about are the penecellins, okay? They're classic examples of beta-lactam antibiotics. The mechanism of action, I already described that in a heap of transpeptidase. And really, for your exam, the coverage of penecellin you really want to know. Because I know like as you study different resources, you see like lists and lists and lists of bugs that are covered by penecellin. I don't think it's necessarily necessary to memorize all those things. But I think there are certain high-yield things you definitely want to know, right? So for example, groupase strap, so strap pyogenes. Remember, this is the thing that causes rheumatic fever. It can cause a post-strap glomerulone fritis. A groupase strap is covered really well by penecellin, okay? Cifillis is also covered really well by penecellin. In fact, one common exam scenario is to tell you about a lady that has... Because usually for syphilis you can maybe give a macrolid every now and then. If you, a person is penecellin allergic. But they ask about a pregnant woman that has a penecellin allergy, but she has syphilis. Penecellin is the best treatment for syphilis in pregnancy. So in other circumstances, you desensitize the lady and still go ahead and give her the penecellin. That's a very common exam question.

So I just thought to mention that. I remember that penecellin also covers Latino miceys very well. Remember those sulfur granules draining from somewhere in the face? Usually the jaw, okay? So those are big things you want to know about penecellin. But that's not, unfortunately. There's other stuff you need to know. So you want to know about the Jarish Hicksheimer reaction, okay? So basically the classic presentation is a person gets penecellin for syphilis. Classically it's syphilis treatment on exams that are associated with the Jarish Hicksheimer reaction. And this does not just occur, penecellin can occur with many of antibiotics, okay? So more classically on the exams is with penecellin, right? So you give penecellin and a few hours later the patient becomes hypotency, they have flushing, they have like this, think of it as an anaphylactoid if you may. So it doesn't look like it's not an anaphylaxis, but it sort of looks like anaphylaxis. Think of it as an anaphylactoid presentation, okay? Usually again, it shows up a few hours after getting the antibiotic, classically penecellin. And the mechanism behind the Jarish Hicksheimer reaction is that the box basically spill the nasty stuff into the circulation, and that triggers a massive cytokine release, okay?

In general for this, it's usually pretty self-limited, where you can give like NSAI Ds, like a fairly frequent basis, and then just some kind of supportive care like IV fluids, and they should be fine for the most part, okay? Now the thing is penecellins, they are bound by many proteins in the body, okay? So they can trigger many kinds of hypersensitivity reactions. In fact, I will say for purposes of your exam, you should know that penecellins can trigger type 1 through type 4 hypersensitivity reactions, right? So they can trigger type 1, they can trigger type 2s. So in the type 2s, those are the ones that are probably more often tested on exams. In the type 2 hypersensitivity reactions, right? The penecellin bind to an antigen on the surface of your ret cells, for example, okay? And then that penecellin bind into an antigen is recognized by antibodies from the immune system. Those antibodies, classically IgG or IgM, can activate complement, okay? And when you activate complement, you then get a very nasty immune response, okay? And actually this will be Combs test positive, right? So you can use a direct Combs test to detect this kind of hypersensitivity reaction, right? And think about it if your ret cells are exploding, what would you observe? This is one very nicely they can integrate microbiology, pharmacology, and hematology, slash immunology on exams, right? So think about this, if your ret cells are exploding, right?

You have an un-conjugated hyperbilarobinemia, your haptoglobin will be low, right? So they can basically give you these markers after a person just started penecellin, okay? And then you have to make your deduction as to what may be going on, right? So because your ret cells are exploding with this type 2 hypersensitivity, you get an un-conjugated hyperbilarobinemia, okay? You have low levels of haptoglobin, remember that then binds up hemoglobin, and it's a pretty good indicator of intravascular hemolocelid. Your LDH will be increased, right? Because remember, ret cells heavily express lactated dehydrogenase. Although, I'll just call your attention to another thing related to LDH. Remember, LDH is typically elevated as well in patients that have pneumocystis-jurovetsi pneumonia. Now, the reaction again, to show pretty quickly this type 2 hypersensitivity, especially when the person is not... This is, let's say, like not the first exposure to penecellin. They can get this type 2 hypersensitivity reaction. Like I said, penecellin can also cause a type 3 hypersensitivity reaction. So you could potentially get like a glomerulone fritis like syndrome with penecellin. It can also cause a type 4 hypersensitivity, but that's not very commonly tested. So I'm going to keep going with that because we have more fish to fry here, I guess. Now, the next drug class I'll jump into at the anti-staff lococcal penecellins, okay?

Again, they all have the same mechanism of action in hippy transpeptidies, okay? The drug names you want to remember here, you want to remember methecellin. No one really uses this stuff anymore because it causes a kind of intra-renol esotemia. So it causes acute intestinal nephritis. I'll talk about that in a bit. So no one really uses methecellin, but it's an anti-staff lococcal penecellin. So it covers MSSA methecellin sensitive stuff, or else, okay? Other drugs in this class include drugs like napcellin, oxacillin, dichloxacillin. These drugs are actually resistant to beta-lactamesis. It's super high yield to know this fact. Because many people have said, oh, every beta-lactam is broken down by beta-lactamesis. That's not true. Okay? These drugs are actually resistant. It's super high yield to know this. They're actually resistant to beta-lactamesis, okay? And the big coverage you want to know again for your exams, MSSA, okay? And the big disease, you'll say that, I'll say like almost 100% of the time, this is the drug treatment on exams, is a patient that has mastitis, okay? So a lady just delivered a baby, and then she has like fever, she has like unilateral breast pain and tenderness, think about mastitis, classically it's caused by staphorias, classically covered with dichloxacillin on exams. Now these drugs, right? They can cause an acute intestinal nephritis, okay?

There are many drugs that can cause AIN, but these are the big ones you definitely want to know, for exams, okay? So the classic presentation for this, right? So like fever, rash, and a varied levels of eosinophils in the CBC, okay? You usually will also see like eosinophils in the urine, right? So like an eosinophiluria, okay? And it usually shows up like a couple of days after you start the drug. It's a kind of intra-renal acute renal failure, okay? And again, I've already talked about the mechanism of resistance to these anti-staphlocococcal penicillins. You alter the structure of transpeptidase, okay? So there'll be a crumosomaline-mediated mechanism of resistance. Now the next drugs I'll jump into are the amino penicillins, okay? The big, the two big ones you want to know here are pyslin and amoxicillin, okay? And pyslin is basically the IV formulation, so remember the I in ampysillin for the I in IV, and then amoxicillin is the oral formulation. Remember the I in amoxicillin for the I in oral. Pretty nice, we remember that. And these drugs, they are in fact susceptible to beta-lactamesis. That's why usually add on beta-lactamase inhibitor with these drugs, right? So like ampysillin usually adds or backtam, but amoxicillin usually adds clavolanic acid. So what do these drugs cover? The big, big thing you want to know is Listeria, okay? Pyslin is the drug of choice for the treatment of Listeria. Remember Listeria, right?

If a mom consumes like deli meats or soft cheeses, and then she delivers a steel bond feeders with abscesses everywhere and like generalize the dima, you're thinking about granuloma torsis and phanticeptica, okay? You generally treat that with your triglystereosis with ampysillin. Now also think of Listeria if a very young kid or a very old person has meningitis. In fact empirically physicians will routinely add ampysillin to the drug regimen for those people just to make sure they are covering Listeria because Listeria is pretty fatal if it's not treated, but the treatment is pretty simple. Ampysillin. Now the amino penicillins also cover like gram positives, gram negatives, but again the big thing I want you to remember is Listeria. Another high yield association we want to know with these drugs is the rash with EBV. Remember EBV is the cause of infectious mononucleosis and hopefully remember the receptor that EBV uses to sneak into B cells is CD21. It's just one of those bizarre things that love to test on exams. Now if a patient gets an ampysillin or amoxysillin or any other kind of amino penicillin and then gets a rash, okay? Or you examine the first thing you want to think that they have is EBV. Your next step would generally be to get a monospot test and they will have a monospot positive test because they have EBV. Now another thing with ampysillin and amoxysillin is they can actually cause CDF colitis.

So your friends at the MBM have realized that everyone has memorized that. Oh you take clinder, you get CDF colitis, you take clinder, you get CDF colitis. So that's becoming more and more de-emphasized on exams, especially on step 2cK. Okay, so if a person has like a false million watery nasty diarrhea, after they took an aminopenicillin, don't be afraid to pick CDF as the inciting agent. Okay, and remember for CDF colitis, you're classically treated like metronidazole or you can give oral, not IV, oral vancomycin, right? Because it's not reabsorbed, so it stays in the jet tracks and kills off the bugs. Okay, you can also give phidaxomycin or in some cases you can actually try a fickle transplant. Okay, but in general, metronidazole is first life for the treatment of CDF colitis. And remember with metronidazole, right? You don't want to take booze alongside because metronidazole inhibits as a toutahide dehydrogenase, so you can get a di-sulfur effect with metronidazole. In fact, I'll just say it's not always true, but in general. Any drug that has azol, this is like a good approximation to keep in mind for your exam. A drug that has azol in its name usually can exert a di-sulfur effect, because it inhibits as a toutahide dehydrogenase. But metronidazole is the big one that's classically tested on exams. Now, ampicillin, right? You can usually paired up with sobactem, I already talked about that. And moxicillin can paired up with clavolanic acid.

Okay, now the next drugs I'll talk about that are penicillins and the antistutomono penicillins. Okay, think of them as the C penicillins, if you may, or the U penicillins. Very easy to remember these drugs, they all end in like cillin, like tycarcillin, piperacillin, carbonicillin. And the big thing they cover on exams, you want to know is sodomonas. So, the patient has like a burn wound and it smells like grape, so their skin looks blue, think of a sodomonal infection. Sodomonas is also classically an infection in patients with cystic fibrosis. In fact, it's the most common cause of pneumonia in cystic fibrosis patients once they get past the age of 21. Prior to the age of 21, that's more stuff-orious territory. Okay, these drugs in addition to covering sodomonas, they are pretty broad spectrum. They cover gram positives, they cover gram negatives, they actually cover some aneroves as well. Okay, and high yield to notice, these drugs are susceptible to beta lactamases. Okay, that's why we combine piperacillin with tesobacter, okay, to make a zoosin, right? You hear of this in your third year, think of zoosin as vitamin Z, because everyone gets that stuff in the hospital these days. Okay, now the next drugs we'll talk about are the cephalosporins, and I'll see some stuff about sodomonas at the end.

Now, the cephalosporins, they're also a kind of beta lactamantibiotic, and again, you won't remember the mechanism of action, they may be transpeptidies, being they're done, they've talked about that already. There are five generations of these drugs, okay, and there are many names you need to technically should memorize for these drugs. But I'm just going to mention a few, these are the ones I see that commonly shop on exams. So if you're trying to cut down on the amount of memorization you need to know, these are probably a good list to know. But everything I say here about these cephalosporins are probably high yield to know for exams. So probably pay attention to this breakdown list. For the first generations of those sporins, the big one you want to know is cephalzolin, okay, cephalzolin, if you're going into surgery or you're doing a surgery rotation, this is the drug that's affectionately referred to by surgeons as anceph, okay, anceph is cephalzolin, it classically covers aneropes, that's why it's usually before most surgical procedures, okay. So the big thing you want to know for generations of cephalzolin covers aneropes. The second generation, I'll just know these names like cephalzolin, cephalzolin, cephalzolin, cephalzolin, and wouldn't necessarily worry about the drug coverage. I mean it's in first aid, I'm sure you can memorize it, but those are very, rarely tested. Now, gen 3 tested very well, okay, they cover both gram positives and gram negatives.

The big ones you want to know here, the first one is cephalzolin, okay, cephalzolin covers my seria, right. So if they talk about a person that has no core rigidity, you perform a longer puncture and you see gram negative diplococcy, okay, think about an iserial infection. I remember if a patient also has a terminal complement deficiency, they have an increased risk of recurring iserial infections. If a patient has, he's taking a Qleuzumap for paroxysamone, an optional hemoglobinuria, right. You're inducing a pharmacologic C5 deficiency. Blue people also have an increased risk of recurrent, of recurrent, of recurrent, my serial infections, right. So those people are classically vaccinated with an iserium and inginidis vaccine, okay. Again, if you also think of my seria gonorrhea, remember, right, if a young person, right. So in general, all people don't get my seria gonorrhea infections on exams, okay. Think of people risky behaviors, right. So like a young person presents with like joint pain, okay. Presents with some kind of like vaginal infection or pinel infection and they have like the pain going from joints to joint. And they have like the TKI on the skin or like paper. You really want to think about my seria gonorrhea infections, okay. You cover that with septraxone. Septraxone is the drug of choice on exams for the coverage of my seria, okay. And septraxone is also good as my seria meningitis profile access, okay. In close contacts, right.

So you could also use rifampin. In fact, the ulcerative is probably the preferred agent. But septraxone can do the trick, superflexic in your flu or in the lung, I'll talk about in a different podcast. You can also do the trick as well. And in general, septraxone, you try to avoid it in like very early life, right. So like in the neonatal period, because it can cause an intra hepatic colistesis. Now, the other third generation agent you probably want to know about is septal taxing, think of it as the pediatric septraxone, okay. It's given in general for most pediatric infections in the first 20 days of life, because you're trying to avoid septraxone. It has very similar coverage profiles to septraxone. And then the third gen agent you should know about is septazidine. Septazidine is the only third generation agent that covers pseudomonas. So it's high you to know that. Now, for your full generation septal sporens, the big one to remember is septoping, okay. The only thing I remember about this drug is it covers pseudomonas. It's pretty broad spectrum. So you can give it to a person that's like septic, but it covers pseudomonas. That's like the big, big, big exam detail you want to know. And then for your fifth generation, the only one I remember is septaroline. It covers mercer. That's pretty much all you need to know about that drug. Now, there are certain generation, generational trends, I guess. You should try to keep in your memory bank with this septal sporens.

As you go from generation one to generation five, increase in gram negative coverage, okay. But as you go from generation one to generation five, you decrease in gram positive coverage. So gen one to gen five, increase in gram negative coverage, gen one to gen five, decrease in gram positive coverage. Just remember one trend and then remember that the opposite of teens for the other kind of bugs. Okay. Again, your third generation, they don't cover this tier. I don't think I mentioned that earlier. Just one of those factoids you want to keep in mind. And the big thing you want to remember here is these septal sporens have about a 10% cross reactivity with penicillin. Okay. So if a person has a history of an aphylaxis to penicillin, you may want to think twice before giving them a septal spore. Okay. Now, carbopenemps, right. So the carbopenemps, again, same mechanism of action, the inhibitranspeptidase. They are actually susceptible to beta-lactamines. Okay. But they are not as susceptible as the other agents, but they are in fact susceptible to beta-lactamines. So something to keep in mind. Okay. And a few things you want to remember, I guess a few drug names. You want to keep in your memory bank with these drugs. Drugs include like meropenem, erdepenem, the endem penem. So you can, you can easily recognize these, right. So like meropenem, erdepenem, duripenem, imi penem. The big thing you want to know about these drugs is that they cover gram positives. Okay.

They cover gram negatives, they cover pseudomonas, they cover anaeropes. These drugs are amazing. Okay. But here's the thing. If you have an infection that is resistant to tributycopenem, that patient has a huge, huge, huge problem. Okay. They are very few things. Carbopenemps do not cover it. So if you have carbopenem resistance, then that patient has a big problem. That's when you usually resort to like very nasty supertoxic antibiotics. Okay. So, these drugs, the big things you want to know here is the increase the risk of seizures. The mechanism behind that, I don't think it's, er, you weren't a huge discussion right now. We have more important things to discuss, but they do increase the risk of seizures. But one big thing you want to know here, because they love to test this, is how a person can have some kidney interactions with imi penem. Okay. So let's talk about it. So the thing is, imi penem can be broken down to inactive metabolites by a kidney expressed enzyme. It's known as a dehydropeptidase 1. Okay. So if you have a lot of dehydropeptidase 1, you will not get a lot of benefit from imi penem. Okay. So in general, if a patient is getting imi penem, okay, you add sila-statin as a drug combination, because sila-statin works by inhibiting renal dehydropeptidase 1. Okay. In fact, I know there is this nice first aid mnemonic that with imi penem, the kidney is last in with sila-statin. I don't know if that helps you remember that. Okay.

So you give sila-statin when you're giving imi penem, because you want to inhibit renal dehydropeptidase 1. That's one thing. But the other thing, and this is more, is just one of those bizarre things I think, maybe begin to shop on future exams. I don't think this is something necessarily disgusting like for a state or most review resources. But it's just one of those things I'm sort of predicting, may shop on exams in the future, because it's becoming very big in the literature. But the thing is sila-statin actually has some beta-lactamies inhibitor activity. So it actually decreases bacteria resistance to the kaba penemps. Okay. And another use sila-statin is beginning to find, I guess, at least in the literature for now, is that it's a renal protective agent. But by yet, I guess this has not fully been elucidated, right? But in fact, most of this is pretty sketching the literature. But there's a lot of studies coming out on this. The thing is, by inhibiting dehydropeptidase 1, sila-statin protects the kidneys. And it protects the kidneys not just when it's administered with kaba penemps like a marrow penem or imi penem, but it actually protects the kidneys when you administer with drugs like vancomycin or cyclosporin. Remember, that's your calcium urinary inhibitor that explodes the kidneys. Or even like cisplatin. Remember cisplatin is a nephrotoxic platinum analog. You actually protect the kidneys.

If a person is getting, if a patient, or I guess a rat, if you're talking about a study, is getting sila-statin in addition to these nephrotoxic agents. And for imi penemps specifically, some studies have shown that by inhibiting dehydropeptidase 1, which is heavily expressed at the proximal convoluted tubules, you decrease the reabsorption of imi penem or its inactive metabolites. So you prevent them from accumulating in the proximal convoluted tubule where you then get toxicity with those drugs. There's some other stuff in the literature that says that, oh, you're decreasing oxidative stress or decreasing the rate of apoptosis of proximal tubular cells by giving sila-statin. But just sort of keep these like fins in mind as what may bizarrely show up on an exam, right? Because I mean, as you probably already know, first aid does not cover, it covers most and you probably destroy step one if you knew everything in first aid. But there'll be questions on step one you see that are not in any resource. So this I think sort of fits that bill pretty nicely as something that may just put an exam but you've never seen anywhere. Okay, now the last few drugs I'll talk about, right? So I'll talk about Astro-Nem. This is a monobacter. Again, it has the same mechanism of action. It inhibits transpeptidase, but the protein it binds to is a different kind of penicillin binding protein. Okay, it binds to penicillin binding protein 3. And by doing that it inhibits cell wall synthesis.

And the thing is because it binds to a different kind of penicillin binding protein, you actually do not have any cross reactivity with like the hypersensitivity you get with the penicillins with Astro-Nem. Now, a big thing you want to know about Astro-Nem is it does not cover gram positives. It covers only gram negatives. It's very high yield to know that for exams. Astro-Nem only covers gram negatives. Okay? So it covers pseudomonas, right? So it's one of those drugs you can use to treat to the monas. And this is a super clean drug. There's essentially no side notable side effects, I guess, for exams that you need to worry about. Now, DAPTO-MICEN. So these, the last group of drugs I'll talk about, I'll just sort of like say like two or three things about them. DAPTO-MICEN. It's a drug that covers gram positives really well. Actually, it does not cover gram negatives. So remember the PIN DAPTO-MICEN for the PIN gram positives. Okay? So this drug has a lipid tail, helps it insert into cell membranes. Well, I guess you can see cell wall-suiting inserts. And when it inserts, you basically have the cell exploding. And you basically exert a bacterial side effects that way. Okay? This drug only covers gram positives. It covers like MRSA, covers Versa. So then, Comixen resistance, staff, or else, also covers VRE. While we're on it right now, right? DAPTO-MICEN covers VRE. But another high-yield drug you want to know that covers VRE is the 50th inhibitor linesolate.

Linesolate also covers Van Comixen resistant and terracoccus. And the big side effect you want to know, DAPTO-MICEN is myopathy. Okay? It can cause a skeletal muscle damage, just like statins and your fibres. So talk about those when we get to cardiovascular pharmacology. Now, Bacetricin is another cell wall inhibitor. You use it for intranasal, staff and strap infections. That's what I'm going to say about that. Van Comixen, I guess, I'll see more than two to three things above Van Comixen, because it's kind of high yield to know for example. But the big thing with Van Comixen is Van Comixen already talked about its mechanism of action. It essentially covers an Allen in residue so that transpeptidides does not have access to that Allen in residue to cause cross-linking and formation of a bacterial cell wall. Okay? And the mechanism of resistance to Van Comixen is that you substitute the Allen in for lactate. When you substitute that Allen in for lactate. So the mechanism of resistance of Van Comixen already talked about it. You basically substitute the Allen in for lactate. Van Comixen doesn't bind so you lose its activity. And again, you want to know that Van Comixen only covers grand positives. So these only covers grand positive drugs. Deptomixen is one. Van Comixen is another. So just you want to keep those in mind. You're licensed. You're deptomixen. Van Comixen. So the cover, Van Comixen obviously covers Mercer. When you give it early, it covers C-Diff.

Again, because it's no way absorbed. So you're steasing the GI tract and kills off the buck. Now, Van Comixen. Some big side effects you want to know. One is a red man syndrome. You definitely want to know that. Van Comixen is one of those drugs that has an anti-histamine. But it has very powerful anti-colonergic activity. So you can use it for the acute dystonia. That a person gets with a taken on your leptic. Another thing could also be slow down the infusion rate of the Van Comixen. Van Comixen is also auto toxic. The thing is it's a pretty water soluble drug. So you can sort of imagine that. It can acumulate very nicely in endolimp and perilimph. Now you find in the ear. And cause auto toxicity. And again, it's water soluble is created by the kidneys. So that may help you remember that it's nephrotoxic. And remember I said earlier that you could potentially protect the kidneys from the nephrotoxicity of Van Comixen by giving it a statin. Just one of those bizarre things you sort of want to take. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin. And you can use it for the skin.

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Inhibition of transpeptidase, preventing cross-linking of peptidoglycan and thus cell wall synthesis.

Oxacillin/Dicloxacillin (Anti-staph penicillins).

Red man syndrome; Nephrotoxicity due to its water solubility.

Ampicillin (or ampicillin) alone, as it has excellent Listeria coverage.

Beta-lactamases.

Third generation (general trend); Ceftazidime specifically covers Pseudomonas.

MRSA involves altering the transpeptidase structure (chromosomal/intrinsic), while beta-lactamase production is often plasmid or phage-mediated.

Oxacillin, Dicloxacillin, and Methicillin (or other anti-staph penicillins).

Low haptoglobin and elevated LDH (due to intravascular hemolysis of RB Cs).

Ceftriaxone.

Treatment of Gram-positive organisms (especially MRSA); Resistance occurs when D-Ala-D-Ala is substituted with D-Lac.

Aminopenicillins (e.g., Ampicillin, Amoxicillin).

Imipenem + Cilastatin.

Ceftazidime (3rd gen) or Piperacillin/Tazobactam (broad spectrum).

Oxacillin, Dicloxacillin, and Methicillin (or other anti-staph penicillins).

Low haptoglobin and elevated LDH (due to intravascular hemolysis of RB Cs).

Ceftriaxone.

Treatment of Gram-positive organisms (especially MRSA); Resistance occurs when D-Ala-D-Ala is substituted with D-Lac.

Aminopenicillins (e.g., Ampicillin, Amoxicillin).

Imipenem + Cilastatin.

Ceftazidime (3rd gen) or Piperacillin/Tazobactam (broad spectrum).