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See how it goes with that. So, I don't know how many we're actually expecting tonight. But yeah, yeah, it doesn't matter because people who sign up but then they just forget. Yeah, exactly. So, I don't think we thank you. I don't think we'll be expecting the whole 52 but we'll see how it goes and see how many people. Ok, cool. So we've got 5040. Ok, cool. So we'll give it a couple of minutes to see how many people we, we can get and then we'll, yeah, we can give it like five just in case people are late. Yeah, we'll give it five. Hello to everyone who are here already. Hello, everyone. Yeah. All right. Should we crack on? Yeah. Ok. So good evening everyone. And thank you so much for joining us tonight on this absolutely freezing Monday night. I understand this really close to exams and the holidays as well. So we really appreciate you coming along and we hope that this session will be of a benefit for you guys as well. Uh, my name is Matt Parker and I'm the president of the Infectious Disease Society. I'm joined today. By our very talented uh educational lead. Um uh He'll be delivering the teaching session today. Um The way in which we're hoping to structure the, the session today is that room will deliver the teaching session. I'll be in the background to answer any of your questions in the chat and then we'll send you a Google Doc um filled with the questions uh like MC Qs for the end of this session with explanations as well that you can do in your own time. Uh Finally as well, if it's OK with everyone would love it if you'd be able to give us some feedback at the end, um which I'll post to the chat at the end of the session. Once you fill the feedback in, we can also give you a certificate of attendance as well for this session. Er So without any further ado I'll pass you over to everyone. Thanks folks. Yeah. So if we've got enough people, we can just crack on. So as my, I gave a lovely introduction, I'm Verone. I am the teaching lead for the Infectious Diseases Society. And today we're gonna be doing bugs, drugs and scrubs, which is a mouthful. I did definitely did not revise that in front of the mirror. OK. So overview of the session, what we're gonna do is we're gonna have the kind of first half of the session focusing on bacterial classification, your gram staining, your um your Aeros and your anaerobes. And basically just to get your head around, which is which and then we're gonna go on to looking at the chemotherapy. So the antibiotics and things, we're gonna look at me me mechanisms of actions and examples of these kind of things and then move on to things like bacterial resistant, commonly used agents, side effects and then drug related considerations thinking about, you know, who's suitable for antibiotic chemotherapy. And then we're gonna have a little small segment on antifungals and antivirals as well. So in terms of questions, you can ask questions at any point, although it will be quite difficult if you speak out. So I think uh an easier way we can do that is if you pop it in the chat, uh we'll have Matt or one of our other members of the society, just answer them for you. OK. So let's just start off. So let's run through some grand standing stuff. Now, I do understand a lot of you are first years. So I'm I'm gonna try and explain things as basic as they can be. So I am in no way, shape or form insulting anybody's intelligence if I'm explaining things from the very basics. So as we all may know, gram staining is the most widely used differential staining procedure in microbiology. So it relies on a series of staining and decoloration steps to differentiate bacteria according to cell wall composition. Now, there are quite a few steps that are involved in gram staining. But the main step that you're going to need to know is the primary dye. So you've got your primary stain, which is your crystal violet. It's important to remember that you use a crystal violet stain and that's applied to a heat, fixed smear of bacterial culture. Now, there are a couple of other things that you end up adding. But this is the main thing that you do need to remember. I remember needing that for the exams. Now, it's easy to remember this because that's how you're gonna determine the colors that the bacteria show up. As. So gram positive bacteria will appear purple and gram negative are gonna appear pink and I'll explain why. So gram positive bacteria, I, the way that I sort of remember our gram positive bacteria are the thicker ones and the gram negative ones are the thinner ones in terms of the peptidoglycan wall. So gram positive bacteria contain a very thick cell wall composed of about 90%. Hm. I was just wondering, are you still on slide one there or are you moving on slides? I am I'm on the second slide actually. OK. I think it might be a bit frozen for us on our end. I was just wondering, you exit and then reha the slides. Oh There we go, we're back. So we're back now to, to the slide that you're on. Uh and are you, are you able to see things changing now. Yeah. Yeah, we can do. OK. How about I keep it like this? Yeah, that would be perfect. Thank you. Cool. Thank you for letting me know. So the the gram positive bacteria contains a cell wall composed of about 90% of peptidoglycans. So it, that's, that's what I talk about when it's thick, it's a lot thicker than the gram negative bacteria when it comes to the peptidoglycan. Now, that's the main sort of component of the gram positive bacteria, cell wall. So following decoloration, the cell will become dehydrated. And then this multilayered peptidoglycan will retain the initial crystal violet dye. So that's why they appear purple. So that's why it's an important thing to remember that you're dying it with crystal violet. You remember that they will retain the violet because they have more peptidoglycan. So due to the darker color of crystal violet, in contrast to this, your gram negatives, they've got a thinner peptidoglycan layer. So they've got, they've got their cell membrane just like gram positive and they've got their cell wall, but that's composed of, of a very thin layer of peptidoglycan. And then they've got multiple layers on top of that. So they've got another lipid layer on top of that and they've got their lipopolysaccharide layer. So your L PS and they've got a lot of different other components as opposed to the gram positive bacteria, which is mainly peptidoglycan. So the main thing to remember is gram positive peptidoglycan. Remember the pee and the pee. So you've got thick gram positive pepto glycan balls, they're gonna take up the purple, they're gonna stay in purple. But these ones because they have a thin layer of pepto glycan, the outer membrane is partially dissolved and the crystal violet dye is washed out from the cell. So that's one of the steps in dying the actual cell, you're gonna have a wash out thing with alcohol. But because the gram positive bacteria have such a thick layer of pepto glycan that, that, that the stain is not gonna get washed away. So that's why gram negative are gonna stain pink as opposed to gram positive. That's stain purple. Now, it is, it is kind of annoying to remember which one stains which because you know, a lot of people use the acronym of like 0 g positive P and P but this is also p it's really annoying. So the way I think of it is peptidoglycan purple or thick peptidoglycan, it's gonna give you purple. So that's the best way I find it to membrane. OK. So that's not the only step that we go through when classifying bacteria. So you go ahead and, and you classify them based on nutritional requirement. So your, you've got your anaerobes, your Aeros and your facultative anaerobes. You've got sporing and nonsporing, which is a little bit niche in terms of uh different type bacteria. But we'll get to that and formations, mainly chains and clusters. So we're gonna talk about things like staphylococcus and we're gonna talk about streptococcus. So that's just a little bit about gra gra staining. I've got a couple of diagrams which I found that help this one as basic as it is. Um It does help to remember which one stains what? Because they are very similar colors and it is sort of difficult to think it through in your head. So if you remember this diagram, you're gonna be completely fine. And as you see in this diagram, you've got your gram positive, this is all just pepto glycan. So you've got your, you've got your cell membrane, which is the same, the two different types of bacteria. But this one, you've got your thick peptidoglycan over here, your gram negative, you've got a very thin layer of peptidoglycan, but you've got all these other structures. That's why gram negatives are notoriously difficult to treat. So you've got things like lipoproteins, you've got lipid A and these things usually constitute things that we call ex or endotoxins. So that's what we'll explain a little bit later. We've obviously got this entire layer, which is the lipopolysaccharide layer. So that's the way you differentiate them and that's how they're different. And this is a little bit of an easier diagram to see. So you've got your plasma membrane, your periplasmic space and you've got the thick layer of pepto glycans. So that's a gram positive, which stains purple. But you've got your gram negative. If you see this in comparison to this, it's a very, very thin layer and then you've got more on top of that. OK. So going on to classifying gram positive bacteria. Now this is the diagram that hopefully that you've been given in your lectures. And I think it's just a very, very good diagram. I think it really helped me in first year to sort of break it down into, into different sort of um different components with this diagram. So we're not gonna talk about, we're not gonna talk too much about anaerobic bacteria. We're gonna talk more about aerobic. So the first way you're gonna classify them is by shape. So Ky are round and Basili are round shaped, simple as that. So you've got your Ky and you've got your bacilli. Then when we look at our coi we're gonna divide them up into two different parts, which is probably the most commonly known things is the streptococci because they're chains and the clusters, the staphylococci. So clusters means they're sort of clustered up in sort of big circles and chains, which is the streptococci are sort of long chain. So they're in pairs or they're in chains. So you can get diplococcus or um chains of, you know, Kai. So I'm gonna talk a little bit about streptococcus, but we'll be going back to this diagram every now and again. So again, as I said, found in pairs of chains under a microscope, it is catalase negative. So another way you differentiate the two of them is by obviously appearance under a microscope. But whether they produce the enzyme catalase. Now, the way that they test this is, you've obviously got your bacteria in an agar plate. And if the bacteria produce catalase, they're gonna convert hydrogen peroxide into water and oxygen. So you would put hydrogen peroxide and if they are catalase positive. So, Staphylococcus, if you see here is catalase positive, they're gonna convert hydrogen peroxide into water and oxygen and you're gonna see bubbling. But if the catalase negative like streptococcus and they don't produce the catalase enzyme, they're not gonna be able to convert hydrogen peroxide. So you're not gonna see any bubbling. So if, if you're ever asked, what are the two ways to differentiate streptococcus and staphylococcus. One is under a microscope, you're gonna see the different appearances and two is by the catalase enzyme. So that's one important thing. So again, as I said, majority of these bacteria are aerobic, further divided into their hemolytic properties. Now, you've got this thing called the Lance. No, that's not the Lancefield. Sorry, that's the next one. So you've got your alpha hemolytic, beta hemolytic and nonhemolytic sometimes referred to as gamma hemolytic. But just remember as nonhemolytic. So your alpha hemolytic, they partially hemolyze. So hemolysis is the breakdown of red blood cells. So the way that you're gonna test. This is if you, you've got blood agar, you've got an agar plate with blood in it, you're gonna put the bacteria that you're testing into that plate and you're gonna see if these red blood cells hemolyze. So if they, if they're broken down by this bacteria. So the, the three ways that you can get outcomes from this test is you can get partial hemolysis. So the way you know, it's partial hemolysis is it's gonna turn the blood agar green. So it's not gonna completely hemolyze the blood cells, it's gonna hemolyze some of them, but it's not gonna hemolyze the other ones. So you're gonna get so this mix and then you get the blood agar turning green. So, examples of alpha hemolytic. So the partial hemolysis is strep pneumonia, strep pneumonia is quite important when it comes to a lot of cases of pneumonia. A lot of cases of meningitis. Um, it's, it's, it's an encapsulated bacteria. So it's one of these things that you're obviously worried about with immunocompromised people or people that don't have spleens, uh that might be a bit too advanced for the first years, but it's obviously, uh you know, a good thing to know. So it's a, it's an encapsulated bacteria and you've obviously got your strep vids as well, which is known for causing endocarditis. So you've got your, you've got your alpha hemolytic. So that's partial hemolysis, turning it green. Then you've got your beta hemolytic So that gives you complete hemolysis. So you're gonna turn the first, the, the, the blood agar that's red, it's gonna turn completely clear colotis. That's because there's complete hemolysis of the blo blood of the blood cells, the complete breakdown of the blood cells. So, if you look here, beta hemolytic, you've got your strep pyogenes, we'll talk about the group a later. So, strep pyo pyogenes causes pharyngitis, um especially skin and soft tissue infections, like necrotizing fasciitis. So it is one of those um kind of serious infections. So it's worth knowing how to identify them. And that is by complete hemolysis or they are a beta hemolytic. OK. So it's gonna turn in color on this. Next. Lastly, you've got your gamma. So you're non hemolytic again, they're not gonna change, it's not gonna change the blood agar. So it's, it's better to remember them as non hemolytic because it's quite self explanatory that there's no change. So I always found it hard to remember the sort of classification beyond the streptococcus. I felt like it's a lot easier to know. OK, I can see the shape of it. I can see the way it looks. Ok. Well, after that, so you start off with looking at the hemolysis properties and then you move on to the thing called the Lancefield classification. So your beta hemolytic are further classified under the Lancefield class classification. So you've got groups A to G and it's sort of based on the serological specific carbohydrate antigens that you find on the surfaces of these bacteria. So, starting off with group A strep, you've got strep pyogenes, like I mentioned before, that's group A. So strep, we go to beta hemolytic and then we go to group A, that's your strep pyogenes. So you can cause pharyngitis post streptococcus glomerular nephritis, which is a kidney infection and skin infections again, like necrotizing fasciitis. So that's the commonly known sort of flesh eating bug that people usually talk about. Then you've got your group B streptococcus, which is your streptococcus agalactiae. People usually don't refer to it as streptococcal lat. They usually just call it GBS or group B strep. It is quite important in terms of things like neonatal sepsis. Now, group B strep, interesting fact is um you'll find it as a commensal. So it's a normal sort of inhabitant of um vaginas. So you will, you will find it in um sort of the normal commensal bacteria in, in females. And it's important when it comes to neonatal sepsis because sometimes that can transfer to the child when a baby's being born. So it's very important to know about group B strep. So again, over here, you got your strep agalactia or group B strep and important when it comes to neonatal infections and nonhemolytic, which is your enterococcus. It's not, it's not classified as group group D anymore or gamma, but it sometimes can be referred to that So it's, it's useful to know that that's what they used to be referred to. It's usually just referred to as enterococcus SPP. But you've got things like enterococcus faecalis and enterococcus PCI and they're usually implicated in things like uti S. So urinary tract infections and things like infective endocarditis. So basically, you're dividing things up into an easy way of classifying your bacteria. And once you remember the steps you take, OK, after aerobic, I'm gonna look at the shape, then I'm gonna look at the way they stay together. I'm gonna look at the hemolysis and then for the beta hemolytic, I'm gonna look at what group it is. So if you keep that kind of stepwise manner, it's easy to identify things in exams because there could be questions where they say, oh, you know, is this is this gram positive? Is this gram negative? Is it uh Staphylococci? And you'll confuse yourself thinking, oh, what is this? So get your classification straight, know your sort of step wise way to identify your bacteria and you'll be fine. OK. So that's all our streptococcus moving on to Staphylococcus. So keep in mind these are all gram positive. We've not hit the gram negative yet. So Staphylococcus is gram positive, they're found in clusters as we mentioned before and their catalase positive. So like unlike Streptococcus, they are able to produce catalase. And if you use the hydrogen peroxide test, you're gonna find that bubbles are produced when they're placed in the agar plate. So the catalase positive and then they can further be divided into coagulase positive and coagulase negative. So I know that is quite confusing. I found that very confusing. First year II had no idea what the difference between coagulase and catalase was and it was quite a lot to remember. But I think again, if you kind of follow this sort of stepwise manner where you think about what goes to what and and what follows what in terms of classification, you'll be fine. So if, if a staphylococcus is coagulates positive, it's usually staph aureus and staph aureus is the most notorious sort of well known staphylococcus that's out there. So that's coagulate positive. The other ones are coagulate negative. So just think coagulate is positive staph aureus, you don't need to think about anything else. So, Staph aureus produces exotoxins. So like what I was talking about before some, some bacteria have different virulence factors. So, virulence factors are basically the way by which they cause harm to the infectious to the host that they infect. So they can produce exotoxins, enzymes like lipases and hydrolases which sort of break down different structures that they infect. So, a a very um important example of this is something called staphylococcal. It's toxic epidermal necrolysis. It's a mouthful, but basically, basically, it's, it's a kind of shock syndrome where the staphylococcus produces these exotoxins and it breaks down your skin. So see the epidermal, that's all it is. So it's not too much. So, it is a commensal, like a lot of different bacteria. It's a commensal organism of the nose and the perineum. So it mainly inhabits your mucous membranes. So 70% of people have got them in their nose, got them in their sort of genital genital region and it sort of does nothing to you over there. But if you're infected with it, then that can cause problems. So they're further classified into M SSA or Mr SA. Now, the only reason they do that is because M RSA is such a big issue. So MSs A is basically methyl methicillin sensitive staphylococcus aureus. So if it is treatable or sensitive to um methicillin, which is your penicillins, you're gonna classify under MSs A if it's resistant to it. So, Methicillin resistant Staph Aureus, it's M RSA and that becomes an issue because you're not gonna be able to use the typical stuff that you use for gram positives against M RSA. So that's why you get that further classification. So as I mentioned, staph aureus is implicated in a lot of different infections. You can get skin infections like cellulitis, simple wound infections, ranging from small sort of kind of superficial wound infections to abscesses within the body. So, abscesses are basically collections of pus and you know, localized collections of pus and infection that is usually caused by staph aureus. And as I mentioned before, a staphylococcal toxic epidermal necrolysis that can also cause osteomyelitis, that's infection of the bone. So, within the bone itself, you can get infections. It can also cause pneumonia. So typically that follows an influenza infection can cause infective endocarditis. Most common cause of infective endocarditis and also line infections. So that's when you have sort of a central line or you have invasive things going into the body when you're in hospital. And sometimes those can get infected and colonized by staph aureus causing infections. So that's the sort of important thing to know that it, it causes such a wide variety of infections. And the skin infections are, are the most common. And then you've obviously got your coagulator negative, which aren't the most common. They're not very, very commonly seen. You, you can get s staphylococcus cyprotus, which is implicated in urinary tract infections. You can get Staphylococcus epidermidis that is quite important in terms of you can get infective endocarditis because of staphylococcus epidermidis. But usually what you see in these coagulate is negative Staphylococcus is they form biofilms. Now, if you don't know, biofilms are these sort of slimy layers that bacteria form to basically evade or become resistant to, you know, chemotherapy. So they form these films which are really, really difficult to destroy. And because they form these films, it's a lot easier for them to colonize and then to infect. So if you have prosthetics like a prosthetic leg or a prosthetic kind of bone implant or uh especially things like prosthetic valves in your heart. You can get colonization and subsequent infection by staphylococcus epidermidis. So that's why that can cause infective endocarditis typically if less than two months since surgery. So that those are the sort of things that you think of. So remember the biofilm, these coagulate negative ones, especially epidermidis, they cause they produce biofilms which helps them, um, colonize and helps them evade antibiotics. Ok. So we've got gram positive anaerobic vessel. And I know I said that you don't have to pay attention to anaerobes too much. But these are, these are quite important as well. So we'll, we'll talk a little bit about them. So anaerobic spore forming gram positive vessel. And I mentioned earlier that you can differentiate based on, on the fact that some bacteria can form spores. Now, spores are quite a difficult thing in terms of treatment is because spores are very, very resistant to treatment. And that's how a lot of these bacteria reproduce. And that's how a lot of them survive in, you know, in hospitable conditions. So they're typically found in soil and dust, you know, wet kind of soil areas is where you'd usually find them. The probably the most common one that you're going to see and you're gonna see talked about a lot is clostridium difficile. The most common and notorious one that causes gastroenteritis, things like pseudomembranous colitis and toxic megacolon. Now again, those are big words, big infections, but just think of it as the one that causes the bad diarrhea because it is a very, very difficult bacteria to treat. And it usually happens in hospital settings. And the reason it is feared is number one, it's difficult to culture, it is not killed by alcohol gel. So usually you will be told when you get into hospitals that you use alcohol gel and you know that you, you'd think that's fine, but they're not killed off by that because of the spore forming because of the spores. So that's why you need to wash your hands with warm water and you need to wash it with soap because of C diff now because it's difficult to treat. That's why people don't want it spreading around and it is very good at spreading around. So you'll normally see if you end up in the hospital or on your placement. If a ward has got a case of C diff, they're going to be r on really high alert for it. They're gonna be wearing special scrubs, they're gonna be making sure that hand washing is happening a lot more often than it is. So it's one of those feared infections. So again, it's difficult to culture. It usually happens because you use a lot of antibiotics. So if you treat somebody with a lot of different kind of antibiotics that will disrupt the normal gut flora and C diff as a lot of other bacteria are, is a normal commensal that's in your gut. So, if you use a lot of antibiotics, not typically it's the c antibiotics. So things like cephalosporins or clindamycin or co trimoxazole. Again, those are difficult names to remember. I agree for the first years. These are all new names. But again, these are the sort of things that you're gonna have to, you're gonna have to know. But remember the c the c antibiotics are the ones that are gonna cause c diff infection. So again, it's not killed by alcohol gel due to spore production and it's associated with toxic product toxin production. So, endotoxins, like I mentioned before, it's gonna produces endotoxins and that's why you get that severe diarrhea. So other gram positive anaerobic basil to know is clostridium perfringens. So that's typically implicated in gas gangrene. It's not very commonly seen, but it's obviously very good to know about clostridium tetany as a lot of us probably know and probably have gotten, hopefully have gotten tetanus. So that's, that's, that's your infection that's gonna cause these generalized muscle spasms and dystonia. So that's, that's one thing that you've got to be um aware of and clostridium botulinum, which isn't too relevant now because that doesn't, it doesn't really happen that much, but it is used in um uh kind of treatment of spasms and stuff. So that's a an interesting fact. So it causes uh a condition called botulism. So it causes flaccid um flaccidity and things like descending neuroparalysis of the motor and autonomic nerves. So that's just an overview of our gram positives. I do apologize for the slides being very wordy, but I thought that if we're gonna, if we're gonna give you these slides, um it's useful to have all the information or as much information as we can put on them so that you guys can take that home. OK. So next we're moving on to gram negatives. So your staph staphylococcus, your streptococcus, your clostridium, they're all gram positives, all these that we've been talking about gram positives. Now we're moving on to the gram negatives. So again, you've got your aerobic, you've got your, these are the strict ones, they're strictly aerobic. These ones are what you call sort of facultative aerobic. So they don't necessarily need aerobic conditions, but they can thrive in both aerobic and anaerobic. And then obviously, you've got your microaerophilic ones which require a small amount of oxygen. So in terms of your strict Arabic ones, the important ones you need to know are they bacilli and things like legionella and pseudomonas. Ainoa, your aerobic ones are, are classified by the same sort of thing that we did in the previous. So the chains and the clusters, the staphylococcus and streptococcus. So you've got your calci and your bacilli and your calci are Neisseria gonorrhea. So that causes gonorrhea and your Neisseria, mening meningitis. I can never pronounce that which causes meningitis. So the important thing to know are these are diplococci. So there have been numerous times where we get questions where oh this person is presented with this sort of infection, they've cultured the bacteria and they see gram negative diplococci. What have they got? When you see occi, you're gonna think about Neisseria. You're gonna think about Neisseria, gonorrhea or you're gonna think about Neisseria meningitis. OK? And in terms of your aerobic bacilli, you've got small and large, which are your co forms. So your small ones are border tela pertussis. You don't see that often because of vaccinations, but that's the one that causes pertussis or whooping cough. And you've got hemohim cause, you know, um bacterial exacerbations of COPD. It is also one, the, the B variant of it. So, haemophilus influenza B is what the hib vaccine basically, um, immunizes you against. So that's another good gram negative to know about. And then in terms of the large ones, large basilia. So the coliforms, you get, you've got commensal and you've got pathogens. So the commensal are the ones that are just there. They don't usually cause problems and the pathogens are the ones that cause infection. So you've got E coli, you've got Kleb C and proteas again, they're commensal, but you're, if you're infected with them, it becomes a problem. So E coli is usually seen in UTI S, you can see them in wound infections. It is, it's quite varied, but it's probably most commonly seen in uti. So, urinary tract infections are where you will see E coli the most. Again, you've got your klebsiella and your proteus and your gut pathogens. So, these are the ones that are not commence. So you got your salmonella typically. Um, most commonly known, you've got s salmonella typhi which causes your typhoid. And uh you've got shigella and a different variant of E coli which is E coli 0157, which can cause um a syndrome called hemolytic uremic syndrome. So again, it's just useful to know. I don't think that the sort of conditions and the n things are very important for the first years. But it's just important to know the classification of your gram negatives, the, the way that you would culture them, the way that they would appear. So your diplococcus, your coliforms, whether they're commensal and some, some examples of commonly caused infections like urinary tract infections with E coli. And then you've got your microaerophilic ones. So you've got your bacilli, your bacilli are then divided into your small curved ones that your Campylobacter. We're gonna talk about Campylobacter and a couple of others later in more detail. And you've got your spiral ones like helicobacter. OK. So let's look at them in a little bit more detail. So again, you've got your Neisseria spp, those are your diplococci aerobic. So group B is the most common in the UK, but you got to remember that the diplo is, is the main thing because sometimes that's all the information that you'll get in questions. And if you remember gram negative dico think about Neisseria. Ok. So Neisseria meningitidis. So it's, it's a commensal as a lot of other ones are. So nasopharyngeal commensal organism, which can be transmitted through respiratory secretions and it can cause acute meningitis with or without meningococcal septicemia. So again, think about meningitis. Think about your diplococci. Think about nice meningitis. Again, as I mentioned earlier, Neera gonorrhea causes gonorrhea, pelvic inflammatory disease. It's quite self-explanatory from the, from the suffix from the um from the second word. So it's quite easy to remember that you've got these um atypical ones like Moraxella catarrhalis again, difficult names to remember. But the way that I remember them is that I didn't, I basically just had, just knew the way it looked, I could never pronounce it. I could never remember the name of it. As long as you know, the way the words look, you're gonna be fine. So that's an aerobic nonmobile paired cocky causes ent infections and pneumonia. You've got haemophilus influenza, like I mentioned earlier, that's the one that is preventable due to the um the hip vaccine and like strep pneumonia. Like I mentioned long, long time ago in the gram positive section, it's a capsulate bacteria. So it can cause pneumonia as well, just like strep pneumonia. You've got things like vibrio cholerae. So that's not very commonly seen in this country, usually found in Asian countries like India and Bangladesh and stuff like that. Um It causes, causes horrible that rice water diarrhea and the thing that kills you isn't the diarrhea or the infection, it's the dehydration. So that's, that's usually treated with oral rehydration and things like that. So that's another important gram negative to remember. And then you've got your enterobacteria, which I have never been able to pronounce. Those are your coliforms. So as I mentioned, they're the large ones and they're mainly commensal and some, maybe, maybe it's useful, maybe not. But lactose fermentation is used to classify these types of bacteria. So E coli as I mentioned earlier, it's quite, it's probably the most commonly known gram negative. It's a aerobic and a commensal one in the gi tract. So it's present all over your intestines. There are loads of groups of E coli and they're classified according to their antigens. Like I mentioned earlier, you've got your E coli 0157, which is probably the worst one which is gonna cause you things like bloody diarrhea and your hemolytic uremic syndrome. Um But they've got different como components like um in terms of their layers. So you got your lipopolysaccharide layer, your capsule and flagella. So these are all the different sort of virulence factors which helps them survive, helps them evade your immune system, helps them evade antimicrobials. So as I mentioned earlier, they're gram negative. So they've got the thin peptidoglycan layer, but they've got that thick layer of everything else, like their lipopolysaccharide and their exotoxins and all those other things. So it produces a range of toxins. Yeah. And the other ones are important to remember is klebsiella, shigella, salmonella, salmonella, enterica and pseudomonas, aeruginosa. So this colonizes water and soil. It's quite a scary one in terms of cystic fibrosis. So, cystic fibrosis is a genetic condition where um you're left quite immunocompromised. So in terms of respiratory infections, it's quite difficult for people with cystic fibrosis to combat them because they've got a very mucus filled um uh lungs. So it's quite, quite a scary one is cystic fibrosis. So it's a good one to remember and it's a common cause of hospital acquired sepsis. And then, as I mentioned earlier, you've got your Campylobacter. So your small curved bacilli it's usually found in undercooked meat and it's the number one cause of bacterial diarrhea in the UK. So a lot of the times people try to do their own barbecues at home and they undercook their meat and they come into the hospital and they've got horrible bloody diarrhea. So usually Campylobacter. Ok. So that's just a quick run through of your gram positives and negatives. It completely understandable. It is a difficult topic to wrap your, wrap your head around. But I think just repetition and making sure you've got that sort of pho photographic memory to know what's gram negative? What's gram positive? So your staph and your strep, they're positive. The other ones um over here are the other gram negatives. I wish there was a, a really good way to remember. Um like pneumonics, but I've got nothing at the moment. Ok. So moving on to sort of your antimicrobial chemotherapy. So before we start, there's some important terms to get familiar with when we talk about a drug being bactericidal, that means the antimicrobial kills the bacteria. So for example, penicillins, it'll kill the bacteria. Whereas bacteriostatic, it's something that inhibits the growth of bacteria. So, Erythromycin, one of the macrolides, it'll inhibit the growth of bacteria. So it's not gonna kill it, it's gonna make it static stasis. So those are two good terms, you know, sensitive, an organism is considered to be sensitive if it's inhibited or killed by levels of the antimicrobial that are available at the site of infections. So if you, you get a sample of urine, you get a sample from an infection site and you send it away for, you usually send it away for sensitivities. That's what we're looking for. We're looking to see if the organism is sensitive to that antimicrobial. So if it's inhibited or killed by that antimicrobial resistant, if an organism is considered resistant, if it is not killed or inhibited by levels of the antimicrobial that are available at the infection site. So this is quite self explanatory antimicrobial resistance, it's not gonna, it's not gonna be killed by that particular antibiotic M IC, which is minimal inhibitory concentration. It's defined as the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism. So it's important to know um the minimal or the maximum amount of any drug that you give to a person, but especially with antibiotics because of the side effects. So you need to, you need to be able to give the appropriate amount of an antibiotic so that it achieves the desirable effect. So you're gonna be able to kill the microorganism, but the minimal amount that you need to give to prevent side effects. So this is basically the minimum concentration needed to inhibit visi visible growth of a given organism. So M BC, which is minimal bactericidal concentration. So this is for inhibitory. So this is this is related to the bacteriostatic things. This is for inhibition M BC which is minimal bactericidal concentration is defined as defined as the minimum concentration of the antimicrobial needed to kill a given organism. So all these terms are quite self explanatory. It's just important to know them to go over them and to make sure that you know why they actual things. So the reason that you've got this minimal concentration is because you need at least some amount of bacteria and some amount of antibiotic to kill the bacteria, but not too much to cause side effects to the person. So it's about finding that balance. Ok. So roots of admission, you've got topical, you've got systemic and you've got parenteral. So topical is basically just applying to the surface. So you're applying it to the skin, you're applying it to mucosal membranes. So you can apply it to your conjunctiva. You can apply it surface on a surface is basically topical. So they are usually creams and emollients and, and things like that that are applied. Systemic is basically what you're used to. So you're taking and uh usually via tablet or you can take it paraly, parenterally is basically you're, you're bypassing your internal system. So paraly, you're bypassing the oral. So you're gonna give it other other than oral. So again, over here, administered intravenously, intramuscularly or occasionally subcutaneously. So, subcutaneously, it's just skin. So I always found like I never understood what parenteral means. Parenteral is just not entirely not through your gut. So you're not absorbing it through your gut, unlike the oral, which you will absorb through your gut. So moving on to mechanism of action of antibiotics. Now, this is the main thing that they're gonna ask you about in exams and the main thing that I always struggled in first year to remember. So this diagram is quite useful. You've got your three thi three mechanisms that you've got to remember. You've got inhibition of cell wall synthesis, inhibition of nucleic acid synthesis or inhibition of protein synthesis. Now, typically, now this is not a hard and fast rule. As you will see, typically, the ones that inhibit cell wall synthesis and nucleic acid synthesis. They're usually the ones that, that, that are bactericidal. They're the ones that are going to just kill the bacteria. Now, some of the ones that are protein synthesis, most of them, not all of them will be bacteriostatic because they're gonna prevent the bacteria from producing essential proteins, which is gonna halt its growth and make it become static. So again, that's sort of hard and fast rule. We're gonna see we're gonna go through all the antibiotics, the main ones that you're gonna need to know. So you're gonna see which ones are bactericidal or bacteriostatic. So it's a, it's a good, it's a good practice to just know this diagram and just visualize the bacteria in front of you and think OK, what's the, what components of this bacteria are, the antimicrobials going to attack? So you've got inhibition of nucleic acid synthesis or folate synthesis. We'll talk about that in a bit. So you're, you're, you're attacking the DNA, some of them are attacking the cell wall. So you're gonna disrupt the synthesis of the cell wall and some of them are going to attack the ribosomes. So if you think of the DNA think of the ribosome, you think of this, this is just another sort of um sub sub uh category of the sort of nucleic acid synthesis. So I wouldn't worry about that too much. But these are the broad ones that you really need to know. And you're probably familiar with that because of your lectures. So think about the DNA, the ribosome and the cell wall. Ok. So let's start off with inhibition of cell wall synthesis. So the first and probably the most common ones that we're gonna think of are the penicillins and the cephalosporins. So they are the beta lactams. So these are beta lactam antibiotics which disrupt peptidoglycan synthesis by inhibiting the enzymes which are responsible for cross linking the carbohydrate chains. So basically, these proteins that are present in the cell wall or produced by the bacteria are known as penicillin binding proteins. They are the ones that are responsible for the cross linking of these carbohydrates causing cell wall to be synthesized. So, if you disrupt this protein, if the this you've got this beta lactam ring and that binds to the protein that stops it from causing the cross thinking of the carbohydrate chains. So basically, you're stopping the cell wall from being formed properly. So they're inhibiting cell wall synthesis. That's why they're bactericidal. Because if you stop the cell wall from being produced, if you stop the cell wall from being made, you're gonna, you're gonna have the organism killed by autolytic enzymes or you're gonna just have all this fluid rushing in to the bacteria and just cause lysis. So lysis means it just bursts. So you're gonna cause the destruction of the bacterial cell because the cell wall has not been formed properly. So, peptidoglycan is an important structural component of the bacterial cell wall. So as you mentioned earlier, your gram positives, their cell wall is mainly peptidoglycan. So if if you disrupt the enzymes that are involved in its synthesis, you're gonna kill the bacteria. So as we see over here, many gram negative organisms are resistant to benzylpenicillin because of this relative impermeability of the gram negative cell wall. So as we mentioned, gram negative, you've not got that much of pepto glycan. And because these usually these um beta lactams, they target the pepto glycan of the cell wall. You're not gonna have much effect on gram negatives. So you've got to remember that these ones are used for mainly gram positives because of the inhibition of cell wall synthesis. No cephalosporins are, are structurally quite similar to penicillins. They're not the exact same. They are a different group for a reason. You've got different generations of them, which are quite difficult to understand. But I don't think you're expected to know um really, really in detail about the cephalosporins, you are supposed to know that they are beta lactams. They are similar structurally to penicillin. So people that are allergic to penicillin will be allergic to cephalosporins as well. And they're kind of described in generations. So you've got second generation, third generation, fourth generation cephalosporins and they're usually quite broad spectrum as well. So these are the first ones that cause inhibition of cell wall synthesis. Next one glycopeptides. So they also cause inhibition of cell wall synthesis. So your main glycopeptides are vancomycin and teicoplanin. Vancomycin is very commonly used in practice. So those are the two glycopeptide antibiotics in common clinical usage, these both act on cell wall synthesis at a stage prior to beta lactams. So the beta lactams basically inhibit this the the enzyme, the penicil penicillin binding proteins that cause the crosslinking of the peptidoglycan layer. But these these antibiotics, they act on cell wall synthesis at a stage before the crosslinking. So they inhibit an assem, they inhibit the assembly of a pepto glycan precursor. So they're similar to the um beta lactams, they're also bactericidal. So due to their inability to penetrate the gram negative cell wall, they act only on gram positive organisms and resistance among gram positives was virtually unknown. Until recently, you don't need to know too much about the sort of Vancomycin resistant enterococcus. That is a thing but know that they are used for a lot of, of, of gram positive uh infections, pretty serious ones and where they need broad spectrum sort of IV antibiotics. And like it says over here, Vancomycin and tin are not absorbed from the gi tract and are only given paraly. So, not entirely. So they're usually given IV. So toxicity is a very common problem with Vancomycin because of how broad spectrum it is. And because of how powerful of an antibiotic it is, it is gonna cause side effects. So that's why it's given through an intravenous infusion. So you can control the rate that it's given because if you're gonna give an oral one, it's absorbed at different rates. And that's something that you don't want to happen with Vancomycin. So it's given controlled and via intravenous infusion. And it's given carefully for this reason because you want to avoid local tissue damage. It should be infused slowly over a period of hours, like I mentioned, and side effects include autotoxicity. So that's gonna affect the ears, nephrotoxicity because it is renally excreted because it's not absorbed from the gi tract. You're not gonna excrete it via your bowels. It's gonna be excreted exclusively through your kidneys. So that's why it can cause nephrotoxicity or toxicity to your kidneys. So, ear toxicity, kidney toxicity and skin rashes. So there's a thing called Red Man syndrome where you get complete redness of your skin because of Vancomycin toxicity. So, as I mentioned, cannot emphasize this enough. It's important to monitor the trough levels of Vancomycin or predose levels to ensure that the serum drug concentration is high enough to be therapeutic but not high enough to cause toxicity. So I, so remember I mentioned earlier, it's that balance between giving enough to treat the infection but not giving too much to cause side effects because it's gonna be quite pointless if you're treating somebody for an infection but just cause more problems. So, tecoplanine appears to be less toxic than Vancomycin and has an advantage of single daily dosing. So that's, that's one of the advantages of tecoplanine. You don't have to give it through IV, you can just give it in a single daily dose, which is easier in hospitals because IV Vancomycin needs to be very carefully monitored and requires a lot of manpower. So with the occasional exception, it has the same spectrum of activity as Vancomycin and the choice between the 2 may be influenced by cost. OK. So these ones also they inhibit cell wall synthesis. Now, I just think it's important to talk about how the the toxicity of Vancomycin it's very relevant to talk about. But again, it does come under inhibition of cell wall synthesis because it acts at a stage prior to the beta lactams inhibiting assembly of a peptidoglycan precursor. OK. So we finished the cell wall synthesis. So that's what we've talked about. Our penicillins, talk about cephalosporins. Those two together are beta lactams and we've talked about our glycopeptides which are our Vancomycin and tecoplanine. So those are the cell wall synthesis inhibitors. OK. Now we're gonna talk about innovation of protein synthesis. So here we're targeting the ribosome. Yeah. So protein synthesis involves translation of messenger RNA of the ribosome and differences between the bacterial ribosome and mammalian ribosome allows selective action on bacterial protein synthesis. So that basically means that the way the Mrna translates in bacteria is different to the way it happens in humans. So you just want to make sure that it's not gonna inhibit protein synthesis in human cells. So they target things that are specific to the bacterial cells. So our first example of this are aminoglycosides. So the most important aminoglycoside that you're gonna know about is gentamicin. Now, gentamicin similar to vancomycin in terms of toxicity, it needs to be monitored, it needs to be given a controlled rate and toxicity is very common. So this this is the main thing for gram negatives. So all the the the two previous ones, they're for gram positives, penicillin, cephalosporins, glycopeptides, gram positive aminoglycosides like Dantin, they're for, they're for gram negatives. So most staphyloco are also sensitive to amino glycosides but streptococci are not. So it's just another one of those things. I try to do a bit of research as to why streptococcus are not, but there's a lot of complex enzyme and biochemistry stuff. So I won't bore you guys with it. But um streptococcus are not, they're not um sensitive to aminoglycosides. So the way that aminoglycosides like gentamycin act is it binds and inhibits to the bacterial 30 s ribosomal subunit and that messes with the protein production protein synthesis and therefore it's bactericidal. So it's an important, just an important thing to remember that it binds to it inhibits bacterial 30 sri is almost subunit. Ok. So the primary use of aminoglycosides is to treat gram negative infection like I mentioned earlier and they're injectable rather than using oral antibiotics. So, gentamicin is cheap and it's very commonly used. But again, as I mentioned, the serum levels must be monitored regularly to avoid toxicity, toxicity to renal function and hearing is a major problem. So it's similar to Vancomycin in terms of its side effects, not, not by its method of action because gentamicin inhibits protein synthesis, whereas Vancomycin inhibits cell wall synthesis. So their toxicity is quite similar. So it affects renal function. So your kidneys and it affects your hearing. So your autotoxicity, your ears um an important thing to know as well. I mentioned earlier inhibition of protein synthesis. You have your gentamycin and Erythromycin. Some of the ones that inhibit protein synthesis are bacteriostatic and some of them are bactericidal. So as I mentioned earlier, it's not a hard and fast rule that if you inhibit protein synthesis, it's just bacteriostatic. So the this is an example of one and then it's gonna inhibit the synthesis but it's still bactericidal. Ok. Now moving on to macrolides again, macrolides are similar in terms of inhibition of protein synthesis, but they are bacteriostatic. So as I mentioned, they are not going to kill the bacteria, they are going to inhibit its growth and they are going to cause it to become static stasis. So, examples of macrolides are Erythromycin and Clarithromycin. So they inhibit protein synthesis through the inhibition of bacterial, 50 S ribosomal subunit. So, correct me if I'm wrong. But mammalian ribosomes, they have 60 S and 20 S, they have, they have different ribosomal subunits as opposed to bacterial because bacterial have 50 S and 30 s. That's why these antibiotics target only their ribosomes are ribosomes. So it's gonna inhibit the bacterial 50 S ribosomal subunit and that leads to reduced protein synthesis. But they're bacteriostatic, not bacteriocidal. So they're quite similar, but they're not gonna kill the bacteria. Now, the most common time that you're gonna see these being used is if somebody's penicillin allergic. So a lot of people are penicillin allergic and they can't be treated with penicillins. They can't be treated with cephalosporins because they're structurally quite similar. So, as an alternative to penicillins, you're gonna give them macrolides. So, Erythromycin, Clarithromycin, Azithromycin. So they're gonna be able to treat gram positive infections. Ok. So again, you've got uh it's quite difficult to sort of quantify what bacteria are resistant to what and things like that. It's quite difficult to remember. And obviously, I don't wanna take up too much time in that, going through every single bacteria, uh uh antibiotic and talking about all of their resistances. This is sort of an overview. So you know what you need to know, but a significant percentage of staph aureus, strep pes and strep pneumonia stains are resistant, but sensitivity cannot be assumed with the laboratory testing. This is this is not too useful actually. Um but neuro Maros like Clarithromycin have better penetration into the tissue and provide better cover. So lower M I CS, which is minimal inhibitory concentration for organisms such as haemophilus influenza A and H pylori. So it's just useful to know that you'd use them for these infections. Ok. Next, again, we're still sticking to the inhibition of protein synthesis. We're looking at the ribosome itself. So we finish the sidewall, we're looking at the ribosome. You got tetracyclines. So, examples of tetracyclines are, there is an antibiotic called tetracycline itself, which is a bit confusing, but you've got doxycycline as well. So they are quite broad spectrum similar to um gentamicin, similar to gentamicin. They bind to the bacterial 30 S ribosomal subunit and blocks T RNA binding. So they're bacteriostatic, they'll inhibit the growth of the bacteria. So this is different to gentamicin because gentamicin is bacteriocidal. So this thing of gentamicin is a very, very strong bacteria. Uh um antibacterial because it's gonna cause bacteriocidal effects. So, tetracyclines are absorbed well orally and work well against Aes. So things like Lyme disease, you got your Borrelia burgdorferi. Uh that's the, that's the mic um bacteria that causes Lyme disease. You've got chlamydia and you've got h pylori again, tetracyclines work well against them. But again, they're not gonna expect you to know too much in detail. The main things that you need to know is the mechanism of action you need to know that it's gonna bind to this ribosomal subunit and you're gonna have to know that it's bacteriostatic. Um You've got your oxazolidinones. So most common one is Nizol because that's the one that's used against M RSA when a lot of the other bacteria, um A lot of the other um antimicrobials do not work against it. So it's, it's a relatively new class. So they're not gonna expect you to know too much about it. But again, as I mentioned before, you need to know its mechanism of action and you need to know about the M RSA part, the MR it's used to treat M RSA and then similar to that is your cyclic lipopeptide. So, Daptomycin is a new agent, novel agent recently introduced with activity against gram positives in general and M RSA in particular. So when you're thinking of M RSA, just think of your nisolid and your Daptomycin. Again, the names are quite difficult and annoying. You would think Daptomycin is similar to Erythromycin, but it isn't, it's just a question of, of looking at these regularly and sort of having a photographic memory and associating it with the, with the correct class. OK. So that's your inhibition of protein synthesis, moving on to your last mechanism of action. So we've dealt with the ribosome, we've dealt with the cell wall. Now we're gonna deal with actual bacterial DNA. So inhibition of nucleic acid synthesis. So a wide range of antibiotics inhibit DNA synthesis, either directly or indirectly by interrupting the supply of precursors for DNA synthesis. So it is quite, it is quite similar to the cell wall synthesis in terms of uh you know, um directly or indirectly interrupting the sort of either you're attacking the precursor or you're attacking the enzyme that's responsible for it's similar in that way. But again, you're attacking the DNA, not the cell wall. So you've got trimethoprim and sulfamethoxazole. So these two are very, very commonly used in terms of UTI S. So when you, when you go into your later years, um when you learn about UTI S, you will see trimethoprim everywhere. So trimethoprim and sulfamethoxazole inhibit different steps in purine synthesis, important to know purine synthesis is part of the DNA, one of the immuno A that you know, part of the DNA, it's gonna inhibit different steps in purine synthesis and it's used in a combined form in the drug co trimoxazole. So these two combined together is called trimoxazole. So it can be bacteria. It it is bacteriostatic and bactericidal. So it has both sort of properties which makes it quite good um for covering, you know, these sort of uti kind of infections. So, trimethoprim will inhibit dihydrofolate reductase. So it'll inhibit folate synthesis pathway in bacteria. So, again, folate is important in terms of purine synthesis and it's important in DNA as a whole. So if you're not synthesizing this precursor, that's in, that's needed for DNA, it's gonna cause bacterial death. So recently seen increased usage. So sometimes you can see it used to treat chest infections. It, it is, it is usually mostly used just for uti si, I've not really, you know, heard of it being used for chest infections. Um but it can be, of course, it's quite difficult to know. And obviously at first tier level, they're not gonna ask you, you know that much in terms of, oh, is this gonna be used for this? You need to know the common ones. So you're probably gonna be expected to know that trimethoprim or co trimoxazole definitely used for UTI S. Um So yeah, trimethoprim is available on its own and is commonly used for treatment of urinary tract infections. So that's usually caused by E coli. So, moving on to fluoroquinolones, fluoroquinolones such as Ciprofloxacin, they inhibit DNA synthesis more directly. So they provided an extremely useful range of antibiotics. So they're bactericidal, they're just gonna inhibit DNA synthesis. They're gonna kill the bacteria. So they're quite effective against gram negative organisms like pseudomonas, but they cannot, they cannot be used in Children due to the danger of interference with cartilage growth. Now, one of the important side effects that they usually talk to us about fluoroquinolones like ciprofloxacin is it causes achilles tendonitis. It's an interesting fact, you know, so it's gonna um it's gonna cause your achilles tendon in your heel to, to break. And as a result you get uh you can get tendonitis. So that is uh an important side effect. Um You've got neuro quinolones like levofloxacin that may have more activity against gram positives. And they're sometimes used in chest infections. Ok. But at the first year level, it's very important to know that it inhibits DNA synthesis more directly and it's bactericidal and it can be used against gram negatives. OK? And it's not used in Children. Ok. So that's all the mechanisms of action of these antibiotics. So your cell wall synthesis, inhibition, inhibition of nucleic acid synthesis and inhibition of protein synthesis is very important to know at your first year level. So I suggest you drill those into your heads. OK. Now let's move on to bacterial resistance. So an organism is considered resistant to a given drug when it is unlikely to respond to attainable levels of that drug in tissues. Measurement of the antibiotic sensitivity of an organism in the lab is designed to predict whether an infection will respond to treatment with that antibiotic. So it's as simple as you think it is bacterial resistance as if a bacteria is not gonna respond to an antimicrobial or an antibiotic. So you've got two types of bacterial resistance. You got intrinsic or inherent, you've got acquired which are both quite self explanatory, but we'll go through them. So inherent or intrinsic resistance. Some cases, all strains of given species are naturally resistant to an antibiotic. So like I mentioned before. Streptococci always resistant to aminoglycosides. So that's just, that's just what it is. They are always resistance to aminoglycosides. It's not because of anything that they acquired or it's not because of a mutation. It's just how they are. And similarly, gram negatives are always resistant to Vancomycin. So, Vancomycin is only used for gram positives, not gonna work against gram negatives. This is usually due to inability of the drug to penetrate the bacterial cell wall to exert its action. So again, you see the differences between the gram positive and the gram negative cell walls because of the different compositions, you're gonna have some bac uh some anti antibacterials that are just not gonna penetrate through that wall. And it's as simple as that. The more important one that you do need to know about is acquired resistance. So that's when resistance may be present in some strains of the species, but not in others. So they haven't always been resistance, they acquire it somehow. So there are 222 ways in which resistance is required. So you can either have a spontaneous mutation during multiplication of bacterial DNA that can result in this change of structure or function, which no longer allows the antibiotic to act at its target as this target may have changed. So it's all you, you must have studied things about like genetic pressure and, and you know, if you use an antibiotic too much, you're gonna eventually have strains that mutate spontaneously and evolve to become resistant to that. That's what this is. It's, it's one of the methods of acquired resistance is just spontaneous mutation. The other one is uh the genes or genes that code for the resistance can be spread from organism to organism. So you've got your horizontal transfer, you've got your vertical transfer. So your vertical transfer is from sort of when bacteria replicate, you transfer that sort of resistance or your horizontal transfer is when you, you, you sort of transfer the plasmids that confers that sort of resistance. So from species to species or organism to organism. So this is the, this is the most commonest spread mode of spread of resistance and genes can be carried out on plasmids, as I mentioned. So extra chromosomal packages of DNA called plasmids or on transposal. So, packets of DNA that insert themselves into the chromosome. So these are basically the two types of acquired resistance that you need to know about. And this is the most common. So you're gonna transfer it from one resistant bacteria to another bacteria that isn't resistant. So that's how bacteria can become resistant to antibiotics very quickly. So there are a couple of mechanisms of bacterial resistance that we're gonna go through, which are quite important. And the main one that we're gonna talk about is beta lactam resistance because that's quite important when it comes to penicillins and cephalosporins, which are very commonly given. So as we know as we've been referring to before penicillins, encephalos porins are beta lactams. They've got a beta lactam ring and that ring is responsible for binding to these penicillin binding proteins and preventing the cross linking of the pepto Lacten wall. Some bacteria produce beta lactamase. So if there's an ace at the end of it, that's an enzyme. So beta lactamase are bacterial enzymes which cleave the beta lactam ring of the antibiotic and thus render it inactive as simple as that. They're not gonna be susceptible or they're not sensitive to beta Latins because they cleave the ring. So there are several different types of metal act and they have differing patterns of activity against penicillin or cephalosporins or sometimes both most hospital strains of staph aureus produce bet acty and therefore resistant to benzyl penicillin. They are also common in gram negative sli. So the important thing to probably note from that is the staph aureus, staph aureus is pretty well known to produce beal acty. So you're not gonna be able to use your normal penicillins against it. And as we'll, as we'll look through later, you have to use different methods to be able to combat these um beal acty producing um microbes. So there are two ways to combat beal acty. One is to introduce a second component of the antibiotic, which is a betalactamase inhibitor. So you've got your beta lactams, you've got your betalactamase and you've got your betalactamase inhibitors. So it's all quite a bit difficult. But if you break it down, beta lactams are your actual antibiotics. Betalactamase is what's produced by the bacteria in response to this, to break that down. And in response to that, we've come up with betalactamase inhibitors to stop them or to inhibit betalactamase. So I do apologize. It is quite confusing, but it's just easy if you sort of think it through in your head as to what is what and therefore protects the antibiotic from enzymic degradation. So, the best known example is called Amoxiclav, which consists of the antibiotic amoxicillin, which is a very commonly used penicillin and the beta lactamase inhibitor, clavulanic acid. So co amoxyclav, amoxicillin, clav coamoxiclav. So that is one of the ways where we sort of combat this betalactamase production. The second method is to modify the antibiotic side chain itself. So this one, you're introducing a second component. So you're adding your regular. So penicillin, so your amoxicillin and something that's gonna inhibit this betalactamase. In the second method is you modify the antibiotic side chain to produce an antibiotic, which is resistant to the actions of betalactamase. So, the commonest example of this is the antistaphylococcal drug flucloxacillin, which is a modified form of penicillin. Flucloxacillin is resistant to the actions of betalactamase. But for laboratory sensitivity tests, the closely related antibiotic. Methicillin is used to represent this class of antibiotic. So again, the main thing you have to take away from that is, this is a modified antibiotic. You're modifying the side chain, you're modifying its actual structure so that it can resist the action of betalactamase. So remember, flucloxacillin is resistant to the actions of betalactamase. OK. So if you remember these two, the ways that you combat betalactamase, you're fine. OK. This is just a bit of an extra section. I don't think you need to know too much about it, but I've just included it just in case things pop up because you can never know you've got extended spectrum beta lactamases. So those are an increasing problem in hospitals and they're produced by some gram negative organisms which makes it even worse because it's already quite difficult to produce gram uh to treat gram negative infections. These lactamases can break down the third generation cephalosporins as well as penicillins. So they render organism resistant to all beta lactam antibiotics. So, ESBL carrying organisms are selected out by the widespread use of antibiotics and infection control measures are currently put in place to stop organisms from passing from patient to patient. So then as as I mentioned, you've got this genetic pressure. If you're constantly treating bacteria or over treating them, sometimes with antibiotics, you're eventually gonna get strains that produce these spontaneous mutations and they are going to produce betalactamase and they're gonna become resistant to all these things. So they're, that's why they're associated by widespread use of antibiotics. That's why there's a lot of a lot of sort of education and a lot of um caution taken when you're prescribing powerful antibiotics or broad spectrum antibiotics, you're only gonna do them in situations that really require them. So similarly, carbapenemase producing Enterobacter, she also referred to as carbapenem resistant Enterobacter. She are a significant emerging clinical problem. So the term is used to encompass a group of extremely resistant gram negative organisms resistant to carbapenems. So, carbapenems are also similar to your beta lactams also similar to your penicillins, but they're quite broad spectrum, they're quite powerful. They're used in things like really, really serious infections like neutropenic sepsis. So, neutropenic sepsis is basically when you have very less white blood cells and you're basically helpless against even the most um not serious bacteria. So in those sort of situations, you'd use something like carbapenems or car carbapenems because they're very broad spectrum, they're very powerful. So again, this is just highlighting how, you know, big of an issue, antibiotic resistance is and you know, you don't want to be left at the point where there's no antimicrobial options for therapy. That's the thing that people are trying to avoid. And that sort of is made worse by over treating people with antibiotics. So it's just an interesting thing to know. I don't think you're gonna be expected to know too much about this, but just important to remember, you know, how antibiotic resistance works. Ok. Next. So the first way, first way uh of resistance to beta lactam antibiotics is beta lactamase production. But you've also got alteration of penicillin binding protein. So remember when we talked about it earlier, the beta lactam ring will bind to the penicillin binding protein. So the way that anti, the way that bacteria can become resistant to these antibiotics is either by producing betalactamase, as we mentioned earlier, that's gonna, that's gonna break down the actual ring that binds to the protein or they're gonna change the protein itself so that it can't bind to the beta lactam. Ok. So the second way, yeah, second way in which microorganisms develop resistant to beta lactams is by changing the structure of their penicillin binding proteins. The enzymes which are involved in pepto glycan synthesis. So they cause the cross linking of the pepto thean fibers which causes your cell wall to remain rigid. But if you, if you've not got that, if that's interrupted or if that's bound to buy the beta lactams, you're gonna cause the bacteria to die. So, and yeah, which are inhibited by binding of penicillins, cephalins, as I mentioned. So, mutations in PBP genes result in a modified target site to which beta lactams will no longer bind. So instead of attacking the beta lactam ring, they're just gonna change the binding site. So it's no longer gonna be able to bind. Such organisms are resistant to all beta lactam agents. So, penicillins and cephalosporins because they're just not going to be able to bind to it and addition of a beta lactamase inhibitor will not make any difference. So these are the ones which are quite difficult to treat. So the best known example of this and the probably the most widely known of it is MRSA. So that's why it's notoriously difficult to treat in the hospital because you can't even add a betalactamase inhibitor because it's not gonna work. So, methicillin resistant staph aureus or MRSA. So MRSA are now a major cause of cross infection in hospitals and are difficult to treat. So that's why, as you mentioned earlier, things like Lidozol or Daptomycin, which are newly engineered antibiotics. They're the ones that are given for M RSA. Ok. So those are your two methods of resistant to beta lactam antibiotics, your alteration of your PBP and your beta lactamase production. So those are the important things to know a small note unresistant to glycopeptides is not a very common thing. It's a very recent thing that you've gotten things like via so your Vancomycin resistant enterococci, but it's also important to know that it does happen in, in sort of clinical settings and it is something that does exist. So, Vancomycin is, you know, as we mentioned earlier, it's quite a strong antibacterial, very strong antibiotic and it's used to treat gram positive organisms. So it's very unusual to see gram positive organisms developing resistant against it. But again, it's sort of this thing about overtreating and over prescription of, um, antibiotics that can cause this sort of genetic pressure, um, to be exerted on these bacteria to cause them to mutate. And that's the whole kind of basis of antibacterial um, antibiotic resistance. Ok. So again, you don't need to know too much about this. But again, it's just useful to know and I thought I have just include it in the slides. Ok. So now we're gonna move on to um, the actual antibiotics. I do understand that there's a lot of information and it's quite an information, heavy session. So, um I do understand if it is quite difficult to pay attention, but the slides are gonna be going out to everybody and all I'd say is just pay as much attention as you can. Don't be too worried if, if things are stick out of your head or if they're too difficult to retain. Um And obviously, if you've got any questions, pop them in the chat, just a little reminder for everyone. Ok. So commonly used agents, let's talk about the beta lactams, the penicillins that we've gone, been going on and on about, you've got benzylpenicillin, which is a penicillin. G, that's the first naturally occurring substance that was founded by Fleming. So it was the one that he found um through sort of the fungi and that's the one that acts against gram positive organisms with the exception of manager. Ok. Ok. But again, I wouldn't really worry about these things. It is quite a difficult topic to wrap your mind around what is sensitive to what, as long as you know, the basic stuff. So, penicillin is used for gram positive infections. You'll be fine. Ok. So it's still the best choice for intravenous treatment of serious pneumococcal, meningococcal and strep pyogenes. So again, these are your gram positives, uh the, the, the pneumococcal and the strep pyogenes. So just make sure you remember them and if you can remember the meningococcal, oh, well, I'm good, but it's I wouldn't, I wouldn't stress too much about that. Um Phenoxymethylpenicillin is a derivative of benzylpenicillin and that's um got slightly better absorption. This is usually used to treat tonsillitis. So, bacterial tonsillitis, you will use benzylpenicillin. So that's still commonly used today. And I think you would use uh Benzali Benzylpenicillin or a variant of Benzyl penicillin to treat syphilis. So those are some interesting facts that you might wanna know. Um amoxicillin or IC and Ampicillin amoxicillin is quite widely used. It's, it's very commonly used for respiratory infections like pneumonia and things like that. So, um it's got better oral absorption than be benzoil, but it's used to be OK for gram negative activity, but a lot of them were now resistant due to beta actin production. Again, I've just included this information on the slides for you guys, but a lot of this is quite difficult to remember. So I do understand, but just remember again, amoxicillin, it's a penicillin, you're gonna use it against gram positive. So it's gonna cover streptococci and some Cali forms. OK? Co amoxiclav again, as I mentioned earlier, this is the, this is the um antimicrobial that's used to combat beta lactamase production. So you combine your amoxicillin with your beta lactamase inhibitor, clavulanic acid and that extends the spectrum to cover beta lactamase producing coliforms. OK? It's that simple flucloxacillin. Again, this is one of the um modified penicillins. So it is resistant to the actions of staphylococcal betalactamase production. So it's the first choice of treatment in staphylococcal infections. So you've got staph aureus, just give them flucloxacillin. So remember, staph aureus is notoriously known for producing betalactamase and because it's been so widely treated, you're gonna, there, there is resistance developing in it. So that's why you're gonna use um flucloxacillin. And if they're resistant to flucloxacillin, that's pretty much M RSA for which you use. Liside and Daptomycin. Piperacillin. It's um it's a broad spectrum penicillin and it's called extended gram negative cover. So it has useful activity against enterococcus faecalis and it also has antianaerobic activity. So it's got a good spectrum of action to cover serious intraabdominal infection. The main main place you'll see Pillin being used is with tazocin. So you will see kind of um pip taz being used for things like neutropenic sepsis. Like I mentioned earlier. There are conditions hematological conditions where people lose their white blood cells or have dangerously low white blood cells. In that situation, you would treat them with pipracil and tazocin. Tazobactam. Sorry. Uh, tazobactam and resin combined to form tazocin. Ok. But it's now commonly used in combination. Yeah, with beta lactamase inhibitor. So it's a similar sort of mechanism of action of oxy. You've got your, um, your beta lactam penicillin or, yeah, your penicillin and you've got your beta lactamase inhibitor, combine them together, gives you a broad spectrum so that you can attack those beta lactamase producing bacteria. And you've got things like imipenem and meropenem. Those are your carbapenems. So they're close relatives of penicillins and a subgroup called carbapenems. They have the widest spectrum of all. So they're um active against most bacteria including anaerobes. So again, you don't, you, you don't usually see carbapenems being prescribed because they're very broad spectrum. And you know, the thing about broad spectrum is that you don't want to kill off commensal, you don't want to um cause any unnecessary side effects. So it's used again in very dangerous situations. So really, really critically ill people with neutropenic sepsis. So those are the, those are the two pretty radical ones that are used. But the main ones you need to know about amoxicillin, co amoxiclav, flucloxacillin if you know where they're used. If you know why flu clox is used because it's, it's the kind of modified side chain and it's used against betalactam is producing bacteria. And by co amoxiclav is used, you're fine OK. And then obviously you got your cephalosporins. I'm not gonna go on too much about them because they are quite confusing to remember. But as long as you recognize their names, so cephalosporins is just the broad category of the antibiotics. You've got things like cefotaxime. You've got, um, Ceftaz, I can never pronounce them. Ceftrixone is an important one. But if you see the ones with the CS, the CF, the CF, the CF, they're, they're usually the cephalosporins and they're obviously named in terms of their generations. So you've got second generation, third generation ones and they're quite broad spectrum as well. The only thing that you have to sort of be careful about with cephalosporins is that they can be used or they can cause clostridium difficile. So the use of cephalosporins has decreased markedly in the recent years as they appear to encourage c diff. So it's again, your c antibiotics like cephalosporin, clindamycin, cotrimoxazole. Those are the ones that are going to um encourage clostridium difficile because the bro broad spectrum antibiotics are gonna wipe out your commensal and they're gonna cause overgrowth of certain bacteria like clostridium difficile. OK. So again, gram positive, they're beta lactams just like penicillin. So that's the main thing you need to remember that they're, they have strong gram positive activity. OK. Next, again, this is just an overview of stuff that we did we have gone through. It's just uh to include some of the stuff that had, didn't have anything to do with the sort of mechanism of action. So then uh aminoglycosides, that is your your um gentamicin. So they're notably used for gram negatives. So a lot of the ones that you're gonna see are gram positive, but this is the main one for gram negative. So including pseudomonas, E coli clsa, et cetera. So with relatively little resistance seen in the UK, currently, most staphylococcus are sensitive but not streptococcus. So it's just a rule of thumb to remember. Gentamicin is not gonna be able to treat streptococcal. Ok. So you gentamicin and you're gonna monitor it because of toxicity because it can cause ototoxicity to your ears, your nephrotoxicity, which is your kidneys and it can also cause uh your red man syndrome. So, skin rashes. Um you've got your glycopeptides again, parenteral use only your Vancomycin and your T Clanin. Like we went through before we remember their mechanism of action because they are going to inhibit cell wall synthesis and they have got good activity against gram positive, not negative gram positive. So, Vancomycin levels must always be monitored because of the same kind of toxicity. So that's the main thing that the uh gentamycin and Vancomycin have in common is that they have the same kind of toxicity. And Vancomycin is typically given for M RSA if it works against M RSA and Clostridium difficile. So the reason it's given for clostridium difficile per oral. So po is per oral is because it's not absorbed in the gut. It's gonna kill off all the clostridium difficile in, in the gut. So it's just as simple as that. So that's the only situation where you would give Vancomycin orally otherwise al almost always, it's intravenous because it's toxic and you have to monitor the serum levels of Vancomycin. Ok. Macrolides. As we went through earlier, Clarithromycin and Erythromycin, you're mainly gonna use them if somebody is penicillin allergic because they have the same sort of activity mainly against posi gram positive organisms. And they are often used in an alternative to penicillin. Ok. So they're also effective against organisms causing atypical pneumonias. Like I mentioned earlier, things like um legionella or haemophilus influenzae like that isn't mentioned over here, but it was mentioned earlier. And um yeah, Azithromycin is a new macrolide. So it's not very often used, but it is used um newer macrolide, which is useful for a single treatment dose of chlamydia infection. Ok. Again, it's just important to remember what kind of bacteria you're gonna be covering with it. As long as you know, the main points of each of your antibiotics, you're fine and then your quinolones that I didn't. Oh You know, I went through them, um your ciprofloxacin and things like that. So the first generation of quinolones like noli nodes, acid, I can never pronounce that. Um were of limited clinical usefulness. The main ones you need to know about the main one you need to know about is Ciprofloxacin and Levofloxacin because they are, they can be active against gram negatives as well. So again, it's just a question of knowing them, knowing their mechanism of action, knowing what class they belong to. And some of the common things that they, they are treat, they used to treat. Ok. And here are some miscellaneous ones that are important just because they're miscellaneous, doesn't mean they're not important, but they don't belong to those broad classes. So, metroNIDAZOLE, it's quite commonly used. It's effective against anaerobes. So both gram positive and gram negative. That's why it's really good to be given for intraabdominal sepsis. Sometimes if you have a patient coming in which you don't know, you know what the infective cause is, they've got intraabdominal sepsis for whatever reason. And you know, there's no time to um take cultures, you would give the metroNIDAZOLE to cover sort of a broad area of gram positive and gram negative. So just remember the intraabdominal sepsis like intraabdominal infections. Um is why metroNIDAZOLE is given fusidic acid. It only uses as an antistaphylococcal drug. Staphylococcus aureus can develop resistance very readily to this agent. So it should always be used in combination with other antistaphylococcal drugs such as flucloxacillin. It diffuses well into one and tissues and so is useful as Staphylococcal osteomyelitis and pneumonia. Ok. Trimethoprim. As we talked about earlier, it's the, you know, the DNA synthesis inhibitor, it causes it's basically the purine synthesis inhibitor. So it's going to mess with the sort of folate metabolism so that you, it's good to remember its mechanism of action. It's pretty much exclusively used in the treatment of urinary tract infections. It it's not very often used for things like C diff or, or for, as I mentioned earlier, chest infections, not clinically anyways, I've not really seen it being used, but obviously it can be. But the main thing you need to remember is uti so if they ask you this in the exam, pretty much gonna have to know that. So again, as I mentioned, trimethoprim and sulfamethoxazole together are marketed as called trimoxazole. Ok. You got your tetracyclines. So they inhibit the protein synthesis. So they target the ribosomal um subunit S if I'm not wrong. This is a good way. Yeah. 30. Yes. So that's what are targets useful to know that. Um it's got a few applications nowadays. It's it's it can be used for chlamydia. So things like Doxycycline, doxycycline is commonly used for chlamydia. And you've got your other sort of respiratory tract infections which are not very common, but again useful to know it's not, it's not given to pregnant women because it is teratogenic, teratogenic teratogenic means that it interferes with the development of babies in the womb. So you're not gonna give it to pregnant women. You're not gonna give it to Children under 12 as they are deposited in the teeth and bone. And as we mentioned, um yeah, you're not gonna give it to Children. Cool Clindamycin. Clindamycin is the only Leno costs antibiotic. So it's not the same as Gentamicin. It is not the same as Erythromycin. Again. It is confusing. I know, definitely do not want to act like it's, it's not because it is very confusing. So it's the only lenos antibiotic in common use and has good activity against gram positive. So such as staphylococcus and strepto gram, and it also has good activity against anaerobes. So it's got good tissue penetration. That's why I into bone. So it can be used for treating things like osteomyelitis and it can also be taken orally. And again, as I mentioned, it's one of the c antibiotics. So things like um uric Ciprofloxacin, co trimoxazole, Clindamycin and cephalosporins, they can cause um clostridium difficile, which therefore leads to pseudomembranous colitis. Ok. So remember your c antibiotics. Next, Lina olide, it's a new agent. It has activity against MRSA. So if all else fails, if you can't give flucloxacillin, if you can't give any of your penicillins, you're gonna give liside. Ok. And one of the side effects is bone marrow suppression. Next, Daptomycin again, I've been going on and on about this because I never ended up remembering it. So I thought I would just stress on the treatments of MRSA liside. Daptomycin. That's what, that's what, that's what they're gonna be used for. Ok. Famcin, again, very similar name, not, not like the other ones, it's quite difficult to remember. It's a new antibiotic that is bactericidal against C diff. So I think what it used to be or it's still given. MetroNIDAZOLE and Vancomycin are still quite often given. But it is one of the second line treatments if um it doesn't respond to metroNIDAZOLE and Vancomycin. So again, as we mentioned, metroNIDAZOLE is for sort of intraabdominal sepsis. So sometimes that can be caused due to C diff. So metroNIDAZOLE, metroNIDAZOLE and Vancomycin usually used for C diff. But if that doesn't work, you're gonna use something like Foxim Mycin. So again, it has a narrower spectrum of activity and yeah, treatment of adults with first um CDI recurrence. So as I mentioned, so you're first gonna get the metroNIDAZOLE and Vancomycin. But if it recurs obviously on advice of, you know, specialist because it is a specialist treatment you're gonna give Oxamycin. So it's just good to be aware of it. If you see it pop up, you're gonna think. Oh Foxim Mycin, I remember Veron was talking about, you know, C diff, I didn't remember exactly what he mentioned but C diff. So it'll be useful. So you can remember in that way. And as I mentioned earlier, this no Nalidixic acid, I can never pronounce it is urinary antiseptic, but it's not very commonly used, it's not very commonly used at all. And Nitrofurantoin, I've not touched on that yet. So it's usually usually frequently referred to with trimethoprim because it's one of the mainstays of treatment of UTI S. So it's a, it's another um urinary antiseptic agent. It's effective against most gram negatives with the exception of these two, which honestly don't need to remember, it's also effective against some gram positive. So you think uti think of trimethoprim and nitrofuran, those are the main one that even us as four years, we're, we have to know very well. Ok. So that has probably been a very, very big overload of information. So I do understand we're gonna now move on to side effects and toxicity before I go on to this, I'm again, gonna say these slides are very, very wordy. So I understand if it's quite difficult to retain things. The main thing is we want to be able to give this to you after we're done with the presentation so that you can refer to this before your exams. Ok. So we're gonna have a quick overview of the side effects and toxicity. So you can have allergic reactions. So this this can occur because of any antimicrobial. But most commonly you've got your beta lactin. So typically people are penicillin, allergic loads of people are penicillin, allergic. I think it's yeah, 10% of people are truly penicillin allergic. Oh no, no, no, sorry. 10% of truly penicillin, allergic patients will be allergic to closs porins. So that that's why I mentioned earlier. Closin are structurally very similar because they're part of the beta lactam group. That's why you get penicillin allergy associated with cephalosporins as well. So it's important to know that, that, that, that gives allergic reactions. You can have immediate hypersensitivity or you can have delayed hypersensitivity. So it's quite self-explanatory, immediate hypersensitivity is basically your anaphylaxis or anaphylactic shock. So it's extreme life threatening form of this and it forms, it usually follows parenteral administration of the antibiotic. This is IgE mediated and occurs within minutes of administration. So I think you guys have a lot of immunology. So you probably recognize this. This is I ge mediated and occurs within minutes of administration. So characterized by itching, urticaria, nausea, vomiting, wheezing and shock. Laryngeal edema may prove fatal unless airway is cleared. So again, it's sort of like a peanut allergy. It's i it's life threatening. It's, it's gonna cause your, your airway to close up. You're gonna get severe redness and itching and nausea and things like that. So that's your immediate and then delayed hypersensitivity. This may take hours or days to develop. So it's delayed and can have an immune, immune complex or cell mediated mechanism. I'm not gonna go into all the immunology of it. Um But yeah, can have immune complex or cell mediated mechanism. Drug rashes are the most common manifestation, but drug fever, serum sickness and erythema nodosum. It's basically just sort of red blotches of your skin may also occur. So the rest of it is, is, is not too, not too important in terms of first years, but it's, it's useful to know that you can get things like Steven Johnson syndrome with some antibiotics and it's associated with the sulfonamides. So, your skin and your mucous membranes are involved. But if you remember the difference between immediate and delayed hypersensitivity, I think you're good. I think you'll be fine moving on to gastrointestinal side effects. One, the a doctor once told me if somebody asks you about side effects of anything, just say gi upset because everything basically upsets your stomach. So, gastrointestinal side effects are commonly encountered with antimicrobial usage. Nausea and vomiting are common, but diarrhea is associated with toxic production by C diff. So, C diff will produce these exotoxins or endotoxins and that's what is going to cause this nausea and vomiting and diarrhea is the main thing. You're gonna get that severe watery diarrhea. C diff again, we're going to go over this again because it is important and it is difficult to remember. It's an anaerobic gram positive bacillus, which can be carried asymptomatically in the gi tract. So it's a commensal and appears to overgrow normal gut flora du during antibiotic therapy and produces toxins. So again, you have your c antimicrobials that will, if you're treated with them or over treated with them, that can deplete your normal flora and cause c diff to overgrow and cause this disease where you get a lot of diarrhea. So again, it's a spectrum of disease. You can get, just get diarrhea, but sometimes you can get things like pseudomembranous colitis or toxic megacolon. So it's just useful to be aware of these things. So you can't, it's very difficult to culture. See if so as I mentioned before, it, it's not very easy to culture. So it's usually um usually treated empirically, which is without culture. So you're gonna just treat it based on symptoms. Um Sometimes you can use detection of toxin, but um typically you're gonna just treat them. So, treatment is with oral metroNIDAZOLE or vancomycin. And again, that's the first treatment. And if that doesn't work, if that, if, if the C diff is resistant to that, you're gonna give Fox Amycin, like I mentioned earlier. So, and obviously you're gonna stop the antibiotics which have caused the ZZ of infection. So it's a spore forming organism. It's easy for the environment to become contaminated and it's important to clean. So lots of hand hygiene, lots of cleaning. Um when a patient has cluster and difficile in a ward because you're gonna need to make sure you get rid of it. And because it's notoriously known for, for not, not um getting um it's notoriously known for sticking around. So you can't use alcohol hand rub because it's not gonna get rid of those spores. Ok. So, as I mentioned, you got your four CSC cephalosporins, ciprofloxacin, Clindamycin Colox just drill that into your head because that's very important to know. So they are the ones that can precipitate. They're the ones that can cause C diff. Ok. So these are your sort of gastrointestinal side effects. You're gonna get nausea, vomiting, diarrhea. But the main things that you're gonna be worried about when you're giving a lot of antibiotics, broad spectrum ones, especially the C ones is C diff. Ok. Some more side effects. So if you're, if you're treating somebody for a bacterial infection, you're giving them loads of antibiotics to getting rid of the bacteria, you're sometimes getting rid of, of the helpful ones as well, which can cause some other opportunistic infections to arise such as thrush, which is a fungal infection. So broad spectrum antimicrobials as I've been going on about um suppress normal flora in other parts of the body and that can result in the overgrowth of resistant organisms. So like penicillins, broad spectrum penicillins or cephalosporins may be complicated by the overgrowth of yeast. So important organism to know is Candida, albicans, candida infection, that's what's gonna cause your oral or vaginal candidiasis, also known as thrush. That's all, it's just an opportunistic infection that is due to broad spectrum antimicrobials, suppressing the normal and you're gonna get a yeast infection. Basically, you can get liver toxicity. So, I it all depends on the sort of excretion and the metabolism of the drug. Some of them are excreted renally. Some of them are excreted and processed, you know, by the liver. So you can get a variety of side effects. Um things like, you know, elevation of liver enzymes and severe hepatitis. Again, it's not too important for you first years to know too much about this. You should just know that there can be side effects because of antibiotics and they can affect your liver, especially the tetracyclines. So your doxycycline can affect the liver as well as antituberculous drugs. So your ripe drugs. So your rifampicin and your isoniazid and things like flucloxacillin can also cause hepatotoxicity. But again, I wouldn't, I wouldn't stress about stress out about this too much as long as you're aware that you can get hepatotoxicity. And you remember some of the drugs that can cause them like tetracyclines and Isoniazid and Rifampicin, you'll be fine. Ok? And then again, renal toxicity, as I mentioned earlier, you got your Vancomycin and your gentamicin that are excreted renally. They're not, they're not processed by the liver, they're just excreted renally. You can get nephrotoxicity or kidney toxicity. So it is especially important to consider if somebody has preexisting renal disease. So if their, if their kidneys are already bad, if they're in bad shape, you're not gonna give s, you're not gonna wanna give something that makes that worse. Ok. That's all. So again, with all these side effects, with all these antibiotics causing side effects, it, it's, it's important to monitor the levels of these antibiotics and it's important to um be aware of what sort of organs they can affect. Ok. Even more side effects. Lovely. You've got neurological toxicity. So, you know, over here we mainly talk about ototoxicity. So affecting your ears. So your gentamicin and your Vancomycin, as we mentioned earlier, they're gonna cause ototoxicity. You can get optic neuropathy. So that's basically you're damaging the nerves of your eyes. So some one of the antituberculous drugs called ethambutol can cause optic nerve damage. Again, these are just one of those things that you're just gonna have to go through and remember it's a pain in the backside to remember all of them. But it is really useful as long as you can recognize something. So if you see a question stem, you see optic neuropathy and you see one of the options is etambutol. You're gonna say, OK, wait, I remember that. I wouldn't have known that if you'd asked me aside from that, but because I can recognize the two together, that's why I can answer the question. So that's my tip when it comes to these side effects. So you can get things like encephalopathy and convulsions and that may result from high dose penicillin or cephalosporin use and you can get things like peripheral neuropathy. So peripheral neuropathy is basically the sort of nerves at the periphery if they're getting affected, if they're getting inflamed and um sort of broken down, you can get neuropathy. So typical culprits can be metroNIDAZOLE and nitrofurantoin. So again, just remembering what causes what and being able to associate that when you see the two of them. And then lastly, I hope, yes, thank God, we've got hematological toxicity. So they can have a toxic effect on bone marrow which causes selective depression of one of the cell lines. So, neutropenia. So when I was talking earlier about neutropenic sepsis, that's what this is. You can get depression of, you know, either white blood cells or your platelets. Um So you can get things like, you know, inhibition. So because it's called trimoxazole, you've got your sulfonamide and your trimethoprim, they can, they'll inhibit your folic acid synthesis in the bacteria, but they'll also do it for you, which is a bit difficult. So that can cause megaloblastic anemia and things like that. So, it's important to remember the, the trimethoprim and sulfonamide can cause anemia. Um But again, just important to remember that hematological toxicity can happen why it happens because you have, you know, selective depression of one cell line. And just remember trimethoprim sulfonamide and some of the HIV drugs, again, it's really hard to cover really hard to remember. But as long as you remember the common ones, you should be fine. Ok. So going through just general principles of antibiotic treatment, you've got to think about patient characteristics. So age certain drugs are contraindicated in Children. So as I mentioned, ciprofloxacin and just determine and tetracyclines as Well, uh in terms of like um mothers and pregnant women, you have to, you have to know, you have to be giving it to the right age group is what I'm saying. And in even in terms of older people, you know, renal function or liver function might have deteriorated. And it's just a case of knowing all these, all the way that things could go wrong and making sure that you optimize treatment according to that. So, again, renal function, many mic antimicrobials are excreted by the kidneys and they can accumulate in the body because of renal failure because they're not being filtered out. So you will obviously have to adjust for that. You have to monitor that you have to make sure that you're not affecting renal function too much. So, remember your igly coside and um your uh glycopeptides. So your vancomycin and stuff liver function. Again, I mentioned this earlier, things like tetracyclines and um yeah, flucloxacillin, they can cause hepatotoxicity. But it's just, it's just a case of knowing about the function of their organs. And if it's affected, what are you gonna do to prevent further deterioration? Ok. Because you don't wanna make the condition worse. And obviously in pregnancy, you're going to not wanna give things that are teratogenic. So you're not going to want to give your uh tetracyclines, you're not gonna wanna give metroNIDAZOLE or your trimethoprim because trimethoprim is gonna inhibit that folate synthesis. So you definitely don't want that to happen to the baby. So it's just a question of, you know, remembering them um prophylaxis. So prophylaxis is basically, you're getting antimicrobials to prevent future occurrence of infection. So this is indicated in cases where patient has been exposed. They, they've not got the infection. Prophylactic antibiotics are given if somebody has been exposed to highly communicable diseases. So, a very important example of this is meningitis. So if you have been exposed to meningitis, you're given prophylactic um ciprofloxacin or rifampicin. Um So with, with very highly communicable diseases, you're gonna get prophylaxis, but you're going to have to remember that you're not treating it, you're not treating an infection here, you're trying to prevent one. So you have to adjust the dose, you have to make sure that you're not. Yeah. So uh an important principle of prophylaxis is that dosage should cover the period of risk only. So you shouldn't give too much. So again, it's balancing the beneficial effect over the harmful effect of giving antibiotics. OK. And therapy, which is when somebody's actually been infected by it. So when the organism causing an infection is not known, you usually give empirical antibiotics. So empirical is give the word empirical is basically um put before antibiotics when you don't know what's causing the infection. So if somebody comes in with, you know, signs of intraabdominal sepsis or they look like they have an abdominal infection because of their symptoms, you're not gonna wait for a culture or sensitivity, you're just gonna give them empirical antibiotics. OK. So exactly. So an adult admitted to the hospital with community and acquired lobar pneumonia is likely to be likely to be infected with pneumococci. So therefore, you're gonna give something like amoxicillin. So as I mentioned, amoxicillin can treat respiratory infection, especially pneumonia if you suspect that you're just wanna get, get give it beforehand. So again, your intraabdominal, you're gonna wanna give things like metroNIDAZOLE, OK. Drug related considerations. So again, as I've been mentioning, it's just an important thing to be aware of. It's not too important in terms of they're gonna ask you loads and loads of questions about, you know, is this better, is this better? But it's just important to be aware of because they can ask twisted questions sometimes. So it's important to know the spectrum of your antibiotics. So you've got narrow spectrum antibiotics, you've got really broad spectrum antibiotics. So usually what you do is if you don't know what the infective causes, you'd give broad spectrum because you wanna cover a large area or a large possibility of, of different antimicrobials. I mean, bacteria, you want to, you will obviously assume that it could be anything. So you want to cover a broad area. So that's usually when broad spectrum is given. But if you've got sensitivities, you're gonna wanna give narrow spectrum things and it's just all thinking about, you know, toxicity and how powerful an antibiotic is and just being aware of what its spectrum is. So, again, monotherapy versus combination, um you can obviously have synergistic effects between certain uh antimicrobials. You can also uh you know, it's also in the case of things like co amoxiclav. So you've got your amoxicillin and clavulanic acid, those two added together is, you know, combination therapy. So that's basically to um evade the be betalactamase production. So that's one of the things or sometimes you can give multiple antibiotics in some people. So things like c diff you'd give um Vancomycin and metroNIDAZOLE. So they can cover mixed infection or they can have an infect uh enhanced effect. So, synergy and uh or to minimize the development of resistant strains to one agent. OK. So when antimicrobials are used in combination, there are three possible outcomes. You can have an additive effect. So they just add on together. So one plus one is two or they can be antagonistic. So their combined effect is less than the sum of their individual contributions which you probably don't want or they're synergistic. So one plus one is equal to four, they're much more greater than the sum of their individual contributions. So the most common example of this is penicillin and gentamicin in the treatment of streptococcal infective endocarditis. OK. So that's just a good example to know and antimicrobials in combination may have additive synergistic or antagonistic. OK. So that's what we mentioned before as a general rule. The combination of two cidal drugs or of two static drugs is additive or synergistic. The combination of one static and cidal may result in antagonism. So commonly used bacteriostatic drugs include the macrolides, Erythromycin. So those are the protein inhibitors, protein synthesis inhibitors, tetracyclines and trimethoprim. Most of the other major groups of antibiotics covered um is sort of beta lactams aminoglycosides and stuff like that are bactericidal and uh but antivirals are virostatic. So, again, your, you're thinking of your, your mechanism of actions and that's the way that you combine them together. They're not gonna ask you too many questions and what should be used together or what's gonna cause this and that. But if you're aware of the concept, I think you're in the clear, OK. And obviously penetration to the site of the infection, that's important to know um where the actual antibiotic accumulates. So you're gonna have to think about route of administration. So if you've obviously got a skin infection, you're, you're gonna wanna try topical things or sometimes you're gonna try oral things to try and get it to cover that. But things like Clostridium difficile, obviously, as you remember, Vancomycin is typically given IV, but if you've got c diff, you're gonna give it orally because you wanted to target the infection in the gut. So you're thinking about where it's, it's going to where it's gonna penetrate to. Ok. Moving on to a short overview of antifungals and antivirals. I know it has been quite a while and this is a lot of information. So once again, I do thank you everyone for your patience. We're gonna go over this quickly and we'll be done as soon as we can. Again. Antifungals and antivirals, they are important, not as important as your anti antibiotics. So just make sure that, you know that. So we're gonna talk about a few different classes of antifungals. You've got your polyenes, polyene drugs, they bind to ergosterol. So that's present in the fungal cell wall, but not in the bacterial cell wall. So this results in an increase in the permeability of the cell wall and it's active against both yeasts and filamentous fungi. So you're gonna just remember that ergosterol ergosterol is what it will attach to. So, the unfortunate thing is it does bind to other sterols and the most common sterile that we're gonna think about is the ones that humans use and need it, which is cholesterol, which is present in mammalian cell membranes. And it's the reason for their toxicity. So, one of the broad spectrum polyenes is called amphotericin B. So it's the only drug that's available for intravenous use and it's used for systemic treatment of systemic fungal infections. It's not a very common thing, but it can happen. It's important to know that ampho amphotericin B is a broad spectrum B, broad spectrum antifungal. It is extremely toxic and it has a wide range of side effects including renal hepatic and cardiac toxicity. Although new lipid complex formulations of the drug offer a reduced incidence of such side effects. Ok. So it's only used when clinically indicated. So again, with a lot of these broad spectrum treatments, a lot of these powerful treatments only used when clinically indicated and they need to be monitored and they usually give an IV because of their need to be monitored. Ok. Nystatin is also very common polyene drug that you're gonna probably see. Uh it's used regularly clinically. It is available for topical use. If you've got topical, um fungal skin infections, you've got your candida infections. Again, it says over your vaginal candida. Um you can give that but you can also give it in an oral suspension as well. And it, it's, it's not as toxic as amphotericin B because it's not as broad spectrum, but it uh it is a little bit toxic. So again, you're giving it when it's clinically indicated, not otherwise. Ok. And the more commonly used ones are the azoles. So things like fluconazole, itraconazole and uh voriconazole where I've usually only seen fluconazole and itraconazole being used in practice. But obviously, I haven't seen everything. These drugs inhibit ergosterol synthesis and can be divided into the older ones. So the miconazole and ketoconazole and the most recent triazoles. So the ones I was talking about the fluconazole and itraconazole. So, fluconazole has been used widely for oral and parenteral treatment of yeast infections. So it's got no, no activity against the filamental fungi called Aspergillus. So, you've probably heard of Aspergillus, you're not gonna use azoles for Aspergillus, you're gonna use it for your yeast infections. And it doesn't uh doesn't usually have toxicity problems. It is quite frequently prescribed in general practice and, and those kind of situations. So that's why I said that it's more commonly prescribed than polyenes. But it's, it's worth knowing all of these things. It's worth knowing that polyene binds to ergosterol. And it's worth knowing that azoles inhibit ergosterol synthesis. Ok. So, Candida albicans is the most common species of yeast. So that's usually the one that's gonna cause your candida uh candidiasis. So, oral thrush and vaginal thrush. Um but you've got these other ones as well that are not too important. And again, they're used for yeast infections. Um but not your Aspergillus. Ok? Because Aspergillus is usually for the uh usually treated with echinocandins, but we'll get to that. So, allylamines, they are also suppressing ergosterol synthesis. So you can see how important this is in terms of antifungals, ergosterol, but they act at a different stage of synthetic pathway from azoles. The only allyl amine in common use is Terbinafine. So that's, that's an important one that I have heard of being used in clinical practice. Terbinafine is an allyl amine. So it's primarily used against dermatophytes and its clinical use is restricted to dermatophyte infections of the skin. So things like ringworm, things like athlete's foot and uh and nail fungal infections. So, mild infections are treated with topical antifungals. The more serious ones are for oral. Ok. It's used for fungal infections, skin and nails. So if you, as long as you remember the broad kind of stuff, you're fine. You know, echinocandins, echinocandins are the ones that are used for Aspergillus. So, Aspergillus can be a tricky one because sometimes they can colonize the lungs. Sometimes they can cause sort of allergic related things. So it is quite an important one to treat if found, it's not too common, but it's definitely one that you need to be able to treat. So that's, that's why you use your echinocandins. So they inhibit the synthesis of glucan polysaccharide and several types of fungi. There are several members of this group, including caspofungin, micafungin and anidulafungin. I'm not gonna, I'm not gonna try and pronounce that well, but caspofungin fungi is the one that is used quite often. So these agents are fungicidal against Candida species and inhibit the growth of several Aspergillus species. So they're used for serious Candida. Aspergillus infections usually on specialist advice. So again, these aren't routinely prescribed in things like GPS and things like that. They're gonna be prescribed under specialist advice. Ok. Almost done. Got just a couple of antiviral drugs to go through and then that'll be us done. Ok. Antiherpesvirus drugs. The main thing that I want you guys to take away from. This is Acyclovir. Acyclovir is the main one. Ok. I know it can be difficult if they give you all the options with the suffix A VR but Acyclovir is the main one that's gonna be used for herpes. Ok. So herpes viruses are very important because they can become latent. They're an important STD that are, you know, transmitted sexually and you can get things like cold sores and, and, and things like that from that. So the, the herpes viruses include things like herpes simplex. That's the one that was talking about the cold sores and the one that we normally associate with the word herpes, that's herpes simplex virus. You've got virus zoster virus, which is your chicken pox Epstein Barr virus, which is your slap cheek disease and cytomegalovirus. So they're not equally so sensitive to antiviral agents. So you've got different ones that treat different things, but you got to remember the mainstay for herpes. If you were herpes simplex, Acyclovir, that's the main thing. I don't want you to be too sort of brought down by how filled up the fight is just make sure you remember acyclovir. So all the other ones are sort of modified versions of Acyclovir with better bioavailability. Um They'd obviously be given on specialist advice, but the main stuff is sort of acyclovir. Ok. So I'm not gonna go through all of these just in, in question of time, but very much welcome to look through these when we've given the slides off. Ok. Moving on to anti HIV drugs again. I don't want you guys to get too bogged down on the sort of mechanism of action. You know what HIV is? You wanna, you know, it's, it's gonna cause AIDS and it's usually, you know, treated with combination therapy. The drug is the drug that was originally given for, is zidovudine. So that can be given, it is usually given these days. So it's not one of the VRS that's annoying. So if you have the suffix vir, you're gonna think about anti-herpes stuff. But the other ones like zidovudine, you're gonna think about anti HIV. So you've got your um nucleoside analog reverse transcriptase inhibitors. Again, I don't remember ever needing to have really, really known this, but it's still useful information in case they ask you it. Um So you've got things like Narine or efa vas, I've never been able to pronounce them. Um But as long as you recognize the names of the antimicrobials, as long as you associated with that particular infection, like Zidovudine with HIV, that's how I remember it because it's got a V in it. Um That's, that's probably the best thing that you can do. And um you've remember that HIV is, is a virus that affects your CD, four T cells. So your CD four T lymphocytes that is what is affected. So you're obviously gonna measure the patient's viral load and your CD four cell count. CD four plus cell count. Ok. And in terms of prophylaxis, you know, you know, Children who are born to parents that have HIV, that's, that's the main thing that you're gonna be worried about. Ok, then you're gonna go on to drugs for chronic hepatitis B and C again, not too important, but still, still important to know, still important to just be aware of. I don't remember them ever asking about these kind of things. So for this, you'd give Interferon alpha, which is basically part of your own immune response. So you just get external or exogenous um interferon alpha and it can be given with the pegylated form or the nonpegylated form and it usually slows. Um yeah, excretion is slowed and treatment frequency is reduced to a week. So yeah, it's basically just given what your immune system produces. So as long as you remember, interfer and alpha, you're fine and sometimes you can give lamiVUDine or Tenofovir. Tenofovir is an important one that can be used for HIV as well. So remember Tenofovir, OK. But again, these in these treatments can be very complicated. I doubt they're gonna ask you very much on them. I remember getting a question about Acyclovir in my entirety of first year. So I wouldn't worry too much about them, but it's still good to be aware of them. It's a delicate balance. Ok? And last but not least your drugs for viral respiratory infections. So these are things like cure influenza. So, zanamivir and oseltamivir are both licensed for treatment for insulins, influenza A or B. So, again, just a question of remembering them. I wish I wasn't repeating the same thing again and again, but it's one of those things that you've got to remember. I don't think it would be worth knowing the mechanism of actions because they are very complicated. Um, obviously, if you're interested in it, it's very good to read up about, but I wouldn't worry about it too much. OK? And again, it can be treated with Rarin as well. So that's another nuclear set analog similar to these HIV ones. OK. So those are your antiviral drugs and antifungal drugs in a nutshell. And that concludes today's presentation. That was a lot of information. I completely understand that it has been a lot for you guys, but thank you everyone for being very patient and I hope you enjoyed. And if you've got any questions, pop them in the chat, we will be sending the powerpoint as well as some SBA S for you guys to solve. And of course, if you've got any questions or any feedback, it would be very much appreciated. So I'll pass it on to Matt. Thank you, ladies and gentlemen, for everyone. That was one of the most brutal lectures you'll ever receive at med school. It's something you'll need the entire way through med school as well. It was perfectly delivered. So it may seem very complex at this point in time but it, it, it's so important. So, thanks so much for uh for that Ver. Um I'll put three links into the chat for you all. Er, the first one's a sort of summary podcast for uh by the Infectious Disease Society that you can have a look at. Talked a lot about what Vers talked about today. Uh The second one is a 20 question M CQ based on the sort of things that were talking I was talking about today as well and then just the feedback form as well. If you could do that for us, that'd be amazing. Um But other than that, we'll let you go. Thank you so much for your time. Thank you guys for your patience. I know it has been a tough one. Um Yes. Thank you very much. Yeah. Well done for sticking with it guys. Thank you so much. I'm gonna exit the screen sharing right now. If I can also, if you have any questions at all, me and Verine will be around for the next 5, 10 minutes as well, just wrapping things up. So if you, if you have any questions, let us know, I'm just checking. They don't have no questions in the chat while going through. No, there was just one question about nitrofur um and pregnancy, but I've answered that. Yeah. Perfect. Lovely. Thanks guys. Thank you. Well, there are a lot of people I couldn't do this for. Um, so the certifier, the certificates, um those will be done. If you, if you follow the link to do the feedback, as soon as you've submitted the feedback, the attendance certificate will be sent to your email that you've signed up with through mail. So that answers your question. That's great. Thanks very much. There are still people. Oh, yeah, we're just leaving. Cool. Cool, cool. What was our total? How many people overall? We had 40 we had 52 sign ups and 40 people show up so extremely well with that, man. I think that's, that's really good for, for the sign ups. This sort of thing is, is so good for all the years. Uh Which is why it's just good. It's good for everyone, man. Like I was, I found it so useful, like doing it myself because I remember like seeing so many questions and like pass me and stuff where they're just like, oh, what antibiotic causes this or that. So I feel like as it is, it is really useful for everybody. It's grim but it's, it's, it's one of the things, it's like learning a new language. So I know, I know, I know, which is why I sort of feel for you guys, like all the first years because there are all these new names and it's so like I can't even pronounce some of them as well. Oh, same. I think it, it doesn't, the name doesn't really matter as long as you can, like you were saying, as long as you can see what it looks like and remember what it looks like. Yeah. Yeah. Yeah, exactly. As long as you're, like, aware of it, you're, you'll be fine. Yeah. Fantastic. Right. Well, I think I'm gonna stop the live and we'll end it there. Cool. Cool. Cool.