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Skye McKennon (she/her): Hi, Connie and Joanna.
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SMED 175 Podium: Dr. Mckinnon. Can you hear me?
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Skye McKennon (she/her): Now I can. Hi!
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SMED 175 Podium: I had to turn on my mic. Do you want to take over screen sharing for your slides, or do you want me to just run the screens here, or how would you prefer
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Skye McKennon (she/her): What is least disruptive to you in the room, cause I can. I’m I’m happy to like run it myself, but if it. If you think it’ll be too disruptive to switch back after we can do it the other way.
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SMED 175 Podium: Lynn, do you have a preference? I’m happy to run the slides, maybe. Just keep it simple
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Skye McKennon (she/her): Yeah, sure.
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SMED 175 Podium: Cool.
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SMED 175 Podium: I usually have my second screen.
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SMED 175 Podium: Interesting name.
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SMED 175 Podium: Let me see if
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Skye McKennon (she/her): Just to be clear to Dr. Breams, you were gonna go through
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Skye McKennon (she/her): just to the beginning to sorry. I have too many things open
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Skye McKennon (she/her): until like through slide 8. Correct.
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SMED 175 Podium: Yeah, and I’ll the where it says, case one. I’ll hand that to you.
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Skye McKennon (she/her): Perfect. I added a slide slide 9. I can’t remember. I think I did it last yesterday. If you I’m happy to go through it if you want, or you can, too. I wasn’t gonna read through it. It was just like what your picture is, but in a table format
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SMED 175 Podium: Perfect. Yeah, it’s a nice slide.
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Skye McKennon (she/her): Perfect.
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SMED 175 Podium: Okay, this one, you know. Because
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SMED 175 Podium: and
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SMED 175 Podium: to know.
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SMED 175 Podium: okay, we have 1 10 on our clocks. And I’m reminded that the wall clock is slow.
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SMED 175 Podium: So we’re gonna get started.
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SMED 175 Podium: So Dr. Mckinnon is also on the call up there. She’s going to be joining us. You get
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SMED 175 Podium: all of the bug and drug experts in the room at the same time today. And the goal here is this is a review session. So, as I was saying, this is a little, slightly new version of doing reviews where we’re using these consolidation weeks in your schedule to revisit some topics, make sure that we’re bringing them back up with hopefully a little bit of forecasting of kind of next steps. And where you’re going to be going with some of this pharmacology?
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SMED 175 Podium: And because bugs and drugs just show up so often and so much, we feel like there’s, you know, more. Airtime is always good. So we’re gonna largely be going through
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SMED 175 Podium: some active learning, asking questions, prompting your memory stuff that you may have already forgotten. We’ll remember it again, and some multiple choice questions and some practice cases, so should be pretty interactive. Stop and ask questions whenever you need. While I was finding this one, I actually found this one which has nothing to do with antibiotics, but I thought was hilarious. So
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SMED 175 Podium: what disease is being represented by this? By this cartoon?
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SMED 175 Podium: Yeah. Rheumatic, acute, rheumatic fever.
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SMED 175 Podium: I don’t know why the vase with all the stars is just really cracked me up. So okay, so let’s get serious, though. So we’re going to talk about just sort of consolidating and applying some of the knowledge that we’ve already covered. So it really shouldn’t be a lot of new stuff. We’re going to throw back to some antivirals, because we haven’t talked about that in a long time, and just remember that, and then talk a little bit just again, consolidating what we’ve already covered with some practice cases.
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SMED 175 Podium: All right. So let’s talk about antivirals. Don’t look ahead. Answers are all in your slides, so just play along as you’re all just scrolling ahead and looking ahead. Okay, but you just looked ahead. So help your friends out at your table. What are some potential targets or mechanisms of actions, of antivirals. We’ve recently talked about antibiotics, a lot, antibacterials.
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SMED 175 Podium: mechanisms of action with our beta-lactams. But let’s remember way back to just basic virology what are some targets or mechanisms of actions for antivirals?
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SMED 175 Podium: I heard neuraminidase. What is that? That is a drug. It is a type of antiviral. And I think technically like a neuraminidase inhibitor describes that mechanism. But what does it do to the virus? How does it act as an antiviral?
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SMED 175 Podium: So edit it?
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SMED 175 Podium: Yes, so it prevents a step in the antiviral replication cycle and neuraminidase can actually does a little bit neuraminidase inhibitors does a little bit of both of entering and exiting, so releasing of new virions.
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SMED 175 Podium: Okay, what other steps in the viral life cycle or viral structures might we use for antiviral activity?
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SMED 175 Podium: What’s that?
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SMED 175 Podium: DNA replication. Yes, so would that work for many viruses, some viruses which viruses
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SMED 175 Podium: not the antimeral, but like the ones with that need to be activated by the viral kinase.
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SMED 175 Podium: or even more simply ones that have DNA
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SMED 175 Podium: right? So that would that DNA inhibition or inhibiting DNA replication would really only be relevant for DNA viruses. Yep.
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SMED 175 Podium: what else
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SMED 175 Podium: reverse transcriptase inhibitors is a huge category. We get to spend tons of time on that. At the end of 503. It’s really, really fun, because those are my favorite. Those would work for which types of viruses
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SMED 175 Podium: I’ll lose track.
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SMED 175 Podium: They are
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SMED 175 Podium: positive chain. Probably you wouldn’t. But reverse transcriptase inhibitors isn’t specific to the single strandedness or the directionality or the polarity of the genome, because it inhibits what
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SMED 175 Podium: reverse transcriptase. So it’s going to work in viruses that use reverse transcriptase
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SMED 175 Podium: to make DNA from Rna, right? So viruses that use that mechanism which for our point, for our sake, there’s really only going to be 2, 1 in particular, which is HIV. Right?
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SMED 175 Podium: Okay, reverse transcriptase. Good. But not all viruses have reverse, transcriptase or use that mechanism. So what else?
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SMED 175 Podium: Rna Polymerase we have. There’s a term for, like the viral Rna Polymerase. Does anybody remember
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SMED 175 Podium: that human cells don’t have cause?
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SMED 175 Podium: Yes, so Rna dependent Rna Polymerase. Our Rna Polymerase usually is making Rna from like Mrna from DNA. But viruses that are Mrna genetic makeup make Rna from Rna. So they have an Rna dependent, Rna Polymerase. Yep.
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SMED 175 Podium: anything else?
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SMED 175 Podium: I think, that hits on a lot of the like viral mechanism
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SMED 175 Podium: there are. If we think about viral infection, there are other tools we use for antivirals, and so one of them would be
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SMED 175 Podium: here at blocking the receptors or blocking the tropism, so just preventing attachment. In the 1st place, so attachment inhibitors, one of them could be the fusion. So what happens when the virus encounters the cell and has to fuse the fusion inhibitors. We talked about DNA polymerase inhibition, rna polymerase, reverse, transcriptase, rna dependent rna polymerase. Yep, all of those can be steps that we could target
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SMED 175 Podium: maturation. So this would be in the steps that lead to a new virion. And so the example here might be protease inhibitors, things that the virus gets replicated, but then has to actually be packaged into a new virus. And so there’s lots of steps in that process for some of these viruses. And so we can target that step and then that release like we talked about with neuraminidase inhibitors.
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SMED 175 Podium: one of the other areas. We’ll just skip that question. When I mentioned sort of we think about viral infection in general, what other ways of sort of targeting viral infection would be to sort of do things that our body would do so. Antibodies.
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SMED 175 Podium: monoclonal antibodies as a maybe post-exposure, or even pre-exposure treatment against certain viruses, and then interferons is also listed on there on these translation of viral proteins so interferons. That’s again, similarly, we’re sort of using our body’s antiviral mechanisms and actually supplementing it or enhancing it and administering that to help the
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SMED 175 Podium: body fight off, and a viral infection. These are pretty rare, but they are in use. So this table is from the goodman and Gilman’s, and some of these are possible targets. So there are ones that are sort of in development and other ways that we’re looking at trying to develop more antivirals because there is not a ton of them
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SMED 175 Podium: questions on any of that
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SMED 175 Podium: good everybody. Remember it. Does that look familiar? You’re like, yes, I learned that awesome cool. Okay. So I’m going to pass it to Dr. Mckinnon. Then who’s going to walk you through a case
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Skye McKennon (she/her): Great. Thank you so much. And Hello! Nice to see everyone. Are you able to hear me? Can you like wave your hands if you can hear me. All right. Perfect. Okay. And then, just for questions in the room, if you could, please use the
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Skye McKennon (she/her): but like the you know the microphone doodads you have at your table, just to make sure I can hear hear you or stop me, and if you know, please, someone yell, stop me if I miss a comment in the room. So thank you. So let’s start with the case. So we have a 47 year old male who’s immunocompromised because of medications related to a heart transplant. And this patient develops a herpes simplex virus infection of his lower lip.
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Skye McKennon (she/her): So what are his treatment options and you’re probably regretting coming to this optional thing right now, because I’m gonna ask you if you could annotate on your screens on that would be super useful, so I can see what you’re thinking. And I I know it’s not a full room, but if you wanna break up, pick a few screens, and you can tell me what are some treatment options?
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Skye McKennon (she/her): I love seeing everyone’s handwriting. It makes me happy.
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Skye McKennon (she/her): Okay, wonderful. I’m seeing a lot of Acyclovir here.
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Skye McKennon (she/her): Great! And I’m going to. Oh, and I’m still seeing more. If you’re still writing, go ahead because it looks like there’s some other options coming up, too.
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Skye McKennon (she/her): I’m seeing Fam. Cyclavir Valley. Cyclovir. Yes.
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Skye McKennon (she/her): yeah. Beautiful handwriting. My handwriting does not look this nice on when I use the electronic
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Skye McKennon (she/her): pens. Wonderful. Okay, it sounds like we’ve come up with some great options. So thank you. Thanks for humoring me. I appreciate that. And you can spread the love I’m going to ask you to stand up and do this a few more times. So if you want to elect the next person feel free to. So I’m going to clear the annotations now. I think
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Skye McKennon (she/her): one second.
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Skye McKennon (she/her): or maybe I can’t maybe. Oh, thank you, bless you, thank you so much. Perfect! Oh, appreciate you. Thank you. Thank you. Thank you. Okay, so let’s go to the next slide, please.
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Skye McKennon (she/her): Yeah. So you came up with many of the potential options that are possible there. Acyclovir Valacyclovir, which is its prodrug. You could consider Pencyclovir or Famcyclovir, Prodrug Gancyclovir, or Valgancyclivir the Val being the Prodrug and you could Potentially consider Sudofavir or Phoscarnet. So it sounds like many of you identify one of these options.
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Skye McKennon (she/her): which is lovely. And so then, to the next slide.
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Skye McKennon (she/her): let’s say that acyclovir is selected which many of you selected. Well, let’s recall. I know Dr. Bream shared some information on this. Why don’t you can either draw or write out the mechanism of action of acyclovir on your screens.
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Skye McKennon (she/her): What’s the mechanism of action of acyclovir?
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Skye McKennon (she/her): Or if someone wants to verbally participate like, say, that’s fine, too, draw verbal.
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Skye McKennon (she/her): I wanna make sure I leave time for Doctors Rumsburg and Bream. So I’ll maybe give you 20 more seconds here.
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Skye McKennon (she/her): Okay, so I see Viral Kinase, and I’m going to go through. I think you’re on the right path here. This is an image from Goodman and Gilman’s workbook and casebook, but this tells us a little bit about the mechanism of Acyclovir. So just to orient you, I’m going to just use thanks for clearing the screen for me, too. I’m going to use a little
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Skye McKennon (she/her): arrow here.
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Skye McKennon (she/her): So right here
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Skye McKennon (she/her): are you seeing me? Can you flick thumbs up? Are you seeing an arrow on the screen that’s moving around. Yes, thank you. Okay. So we’re gonna start here. We have actually, maybe
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Skye McKennon (she/her): so we had
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Skye McKennon (she/her): sorry. Let’s let’s just draw here. I’m going to make this better. Okay? So we’re going to start here. We have Herpes Simplex here. And so what does it do? The virus itself, while it enters the host cell
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Skye McKennon (she/her): and then it ultimately. This is an oversimplification, of course, but it releases its DNA in the nucleus and basically uses the body host machinery to replicate and produce new viral particles. So where does Acyclovir come in? Well, acyclovir, right here on this image.
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Skye McKennon (she/her): acyclovir. Here this is a Guanosine analog, and then very specific. This herpes, thymidine kinase. Here this monophosphorylates the acyclovir to an active intermediate, which is then further phosphorylated
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Skye McKennon (she/her): and further phosphorylated till we get to Acyclovir, triphosphate and Acyclovir triphosphate can then incorporate into the replicating viral DNA Strand. So it basically
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Skye McKennon (she/her): it competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase, and then it itself becomes incorporated into the viral DNA. And then that causes premature DNA chain termination. So that is basically how acyclovir can halt the herpes simplex virus replication.
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Skye McKennon (she/her): And then I have on the next slide just a slightly, maybe a little more, a little simplified mechanism of action. And it’s in your handout. I know the way that this is like a tall, tall, thin image. So it might be a little tricky. So, but it’s basically showing us here. Acyclovir is here, and then the thymidine kinase, then phosphorylates
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Skye McKennon (she/her): acyclovere, and then we ultimately get
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Skye McKennon (she/her): the acyclovir triphosphate that can then incorporate and and basically halt viral, the Strand. The the viral. DNA,
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Skye McKennon (she/her): perfect. Okay, wonderful. So thank you so much. And so now we talked about Acyclovir’s mechanism of action. So now let’s consider on the next slide possible mechanisms for acyclovir resistance.
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Skye McKennon (she/her): So thinking of its mechanism of action, what are possible mechanisms of resistance.
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Skye McKennon (she/her): and maybe we can just verbally, maybe some brave souls can verbally take a guess
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SMED 175 Podium: Mutation of the viral Thiamidine Kinase
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Skye McKennon (she/her): Absolutely. Yes, absolutely. Thank you.
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Skye McKennon (she/her): And we can go to the next slide. Actually, please. Thank you.
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Skye McKennon (she/her): That is the most common resistance mechanism. So I think you’ve kind of hit the nail on the head. So the most common resistance mechanism is mutated, viral, thymidine, kinase activity, but altered viral DNA polymerase is less common, but can occur. But you hit the nail on the head.
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Skye McKennon (she/her): So that is one way in which mechanism of action can help you rationalize some other. I would try to stress like how mechanism and action can help us, sometimes with adverse effects or kinetics or whatnot. But this is a nice way where mechanism of action can help you reason through a resistance mechanism so lovely.
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Skye McKennon (she/her): Now let’s consider on that. If this individual is treated with Acyclovir, what are some adverse effects or events that we should warn the patient about.
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Skye McKennon (she/her): and you can write, or someone can share verbally. Let’s get a few out there and then I’ll cover a few more
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Skye McKennon (she/her): and then we’ll do a practice board style question
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SMED 175 Podium: I remember the sketchy. The guy had a helmet, so cns symptoms
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Skye McKennon (she/her): Oh, I love it when sketchy hell comes through for you, I love that, and sketchy. The guy had a helmet. Yes, definitely. Thank you so. Yes, there can certainly be central nervous system effects things like altered sensorium, tremor seizures, even extrapyramidal signs. So those are all possible. So yeah, way way to come through sketchy way to come through sketchy
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Skye McKennon (she/her): wonderful. So thank you. And I, I’ll go through a few more on the next slide. But that’s I think an important one
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Skye McKennon (she/her): to remember. Nausea is not particularly unique, because many drugs can cause nausea, but the incidence of nausea is relatively high in individuals who use acyclovir, but the principal dose limiting toxicities of at least ivacyclovir are renal insufficiency, and the Cns side effects that you remembered with the helmet.
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Skye McKennon (she/her): So that’s lovely. But the renal effects are, we think, due to high urine drug concentrations. And then we get a crystalline nephropathy.
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Skye McKennon (she/her): An acute kidney injury can also occur. We can prevent that with adequate hydration and dosage adjustment, if some with renal dose adjustment. So that’s something to keep in mind. But the last bullet is a relatively unique adverse effect. So the thrombotic Thrombocytopenic purpura Ptp can occur. So that is sometimes those things kind of
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Skye McKennon (she/her): end up on board style questions, because it’s a little more unique, of an adverse effect.
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Skye McKennon (she/her): And now we can go to a practice board style question. So this is a practice board style type question. So an investigator, studying the efficacy of antivirals in infected human cells
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Skye McKennon (she/her): actually harvested, human cells are inoculated into 4 cell culture plates live. Varicella Zostervirus is administered to cells on 2 of the culture plates.
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Skye McKennon (she/her): one healthy and one infected cell set or set aside as controls, so in comparison with the control plates. Subsequent application of a guanosine analog to the experimental cell sets induces cell death in the virally infected cells, but not the healthy. So which of the following is the most likely mechanism for these findings.
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Skye McKennon (she/her): and maybe I’ll let you discuss as a group, and then you can circle your answers on the screen
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Skye McKennon (she/her): or write your answer. If you don’t want to circle it, you can write it out.
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Skye McKennon (she/her): I see someone bravely going to to the screen. Thank you.
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Skye McKennon (she/her): Okay? I see phosphorylation by virally encoded thymidine kinase any
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Skye McKennon (she/her): My statistics, teacher always used to say like second opinion, so does anyone agree or disagree?
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Skye McKennon (she/her): Raise your hands if you agree, like wave in the air. So I can see you. Okay, thank you. Thanks for helping me out. I appreciate that. Yes, okay, so it sounds like everyone is in agreement there. So thank you. On the next slide that just highlights that that is the best option.
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Skye McKennon (she/her): and hopefully, this helps you in your thought process when you’re approaching questions like this, hopefully thinking back to the mechanism of actions can be useful in this way, and I’m going to hand it over now to Dr. Remsberg, who’s going to take you through some antibacterial
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Skye McKennon (she/her): case? Questions
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SMED 175 Podium: Can everybody hear me?
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SMED 175 Podium: I’ve caught a lovely virus which is so great that we’re talking about viruses from my daughter. So hence the mask. So if you can’t hear me because I’m muffled, let me know. I will try to
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SMED 175 Podium: enunciate my words even clearer. Okay, so I’m going to be doing a little bit of antibacterial antibiotic review. So some of these concepts have been introduced by Dr. Breams over the last few months. And so we’re going to tie this together and do some foreshadowing of things to come.
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SMED 175 Podium: Okay.
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SMED 175 Podium: So I’m gonna try to clear my the annotations, maybe.
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SMED 175 Podium: How do I clear the annotations. Dr. Brims.
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SMED 175 Podium: Oh, sky! Thank you, Skye. In the in the magic
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Skye McKennon (she/her): It was someone else I don’t want to take coming up
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SMED 175 Podium: Okay, so thinking of mechanisms so very basic, what are the 4 ways that antibiotics work?
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SMED 175 Podium: You can write them, or you can talk about them.
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SMED 175 Podium: So all right, that should be fresh in your mind, because,
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SMED 175 Podium: bid elect hims recently. But what other ways?
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SMED 175 Podium: Okay, I heard protein synthesis.
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SMED 175 Podium: Okay, what other things
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SMED 175 Podium: did I hear? DNA synthesis?
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SMED 175 Podium: Good, good!
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SMED 175 Podium: Anybody. Remember the the final one can also.
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SMED 175 Podium: Here, I’ll show you an image that might jog your memory.
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SMED 175 Podium: Okay, you can disrupt the cell membrane. So there’s like daptomycin, for instance, which can actually make a little channel that disrupts that cell membrane. So this is the image I know Dr. Breens has shown you, so you can inhibit cell wall synthesis, disrupt cell membranes inhibit DNA or Rna synthesis
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SMED 175 Podium: or target that protein synthesis by really interacting with those ribosomes. Okay, the 30 s. And 50 s. Subunits of those ribosomes. Okay, so this is foreshadowing of where you’re going as you talk about more antibiotics with Dr. Breams.
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SMED 175 Podium: So then, back in, when did we do this? September, October? It was a long time ago. We talked about general mechanisms of resistance.
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SMED 175 Podium: Anybody recall what the 3 general mechanisms of resistance are.
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SMED 175 Podium: Okay, efflux pumps? Great yeah. Modified targets.
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SMED 175 Podium: So inactivation, enzymatic inactivation. Great you guys remembered them. Okay, so quick review of that. So you can have limiting drug uptake where the bacterial cell essentially makes it so that the drug can’t get into the cell at enough concentration to have its effects.
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SMED 175 Podium: Okay, so one way that this can happen is through pourins.
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SMED 175 Podium: Okay, down here.
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SMED 175 Podium: Okay, those are going to be expressed on your gram negative bacteria, and so
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SMED 175 Podium: these bacteria will down regulate the
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SMED 175 Podium: the amount of the porons, and so then the drug can’t get in.
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SMED 175 Podium: Okay. The other thing is they can upregulate efflux pumps that will pump the drug out of the cell. And so essentially, you’re getting decreased uptake.
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SMED 175 Podium: Who’s drawing on the image? Is it just doing that we have a ghost?
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SMED 175 Podium: I think we have a ghost. Okay?
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SMED 175 Podium: So then, second thing, modification of drug targets. So I know with the Beta lactams you talked about altered penicillin binding proteins.
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SMED 175 Podium: But all these other drug targets that you’re going to be talking about with Dr. Reams can also be modified in such a way so that the drug can’t bind. So, Macrolides, you can have changes in the ribosomal subunits fluoroquinolines. You can have changes
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SMED 175 Podium: in the binding there and then. You can also have that enzymatic inactivation with those beta-lactamases
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SMED 175 Podium: or the bacterial cell can actually go in and covalently add various functional groups to the drug to make it so, then the drug doesn’t want to. Can’t bind as efficiently with this high of affinity to the binding site.
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SMED 175 Podium: Okay? So there’s acetylation and methylation and all kinds of different things that can happen.
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SMED 175 Podium: So thinking of a case here, we have a 56 year old man who’s brought to the hospital with a productive cough and temperature of 103,
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SMED 175 Podium: and then a chest X-ray reveals pneumonia in the left lower lobe.
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SMED 175 Podium: Okay, so this is foreshadowing where you’re going with your respiratory unit coming up right after obtaining sputum and blood cultures. He started on a penicillin antibiotic.
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SMED 175 Podium: What’s the mechanism of action? Penicillin.
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SMED 175 Podium: remember?
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SMED 175 Podium: Okay?
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SMED 175 Podium: So they bind penicillin binding proteins. What do penicillin binding proteins do
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SMED 175 Podium: huh?
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SMED 175 Podium: Okay, cross-link the peptidoglycan cell. Wall.
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SMED 175 Podium: Okay, good.
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SMED 175 Podium: Okay. So this is a little bit more of that mechanism which I think, Dr. Brains, you’ve covered a little bit.
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SMED 175 Podium: Okay? So just as a reminder.
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SMED 175 Podium: You have glycopeptides that get cross-linked. And so they have
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SMED 175 Podium: these blue residuals. Here are glycines.
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SMED 175 Podium: and then here these gray ones. Right here are d-alanine, and there’s like 2 repeated d-alanine
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SMED 175 Podium: amino acids. And so the transpeptidase comes in and removes this last d-alanine, and then in the process links it to the the next one over here. Okay? And so
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SMED 175 Podium: beta-lactams are essentially structural analogs
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SMED 175 Podium: of d-alanine d-alanine. Okay? And so it’ll go into the binding pocket of that transpeptidase.
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SMED 175 Podium: So the beta-lactam will go in there and then they’ll inactivate it and inhibit that transpeptidase reaction going forward.
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SMED 175 Podium: So bacteria will have lots of different, distinct penicillin binding proteins. And then the affinities for beta-lactams vary. Hence. Why, there’s so much
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SMED 175 Podium: variation, right? Okay? You can’t just use one drug to to treat everything.
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SMED 175 Podium: hey? So it’s quick review and refresher on that.
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SMED 175 Podium: So thinking of our case, if we have this patient who has not improved over 24 h, and the cultures come back.
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SMED 175 Podium: That showing that the strep pneumonia is not sensitive to penicillin. What what
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SMED 175 Podium: bacterial mechanism is happening, or bacterial resistance. Mechanism is happening specifically for penicillin.
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SMED 175 Podium: So so beta optimus, what else is likely happening?
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SMED 175 Podium: Yeah, also, penicillin binding proteins. Right?
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SMED 175 Podium: Okay?
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SMED 175 Podium: But technically, you could also have efflux like increased efflux out of that cell.
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SMED 175 Podium: Okay, so that’s mostly what’s gonna be happening.
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SMED 175 Podium: Okay? So now, we’re going to do some Pk Review, which is everyone’s favorite.
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SMED 175 Podium: So back in September, October, we talked about concentration, dependent and time dependent killing of antibiotics.
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SMED 175 Podium: So I’ve got 2 different dosing schedules here drug A and drug B, which one of these schedules would you want to have for Beta lactams?
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SMED 175 Podium: Do you remember if they’re time dependent or concentration dependent.
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SMED 175 Podium: Yeah. So beta-lactams are time dependent killing. So it? Which one of those dosing schedules would you want? Would you want drug a where you give the drug once a day at a high dose.
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SMED 175 Podium: No, you would want drug. B,
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SMED 175 Podium: okay, so you would want to have
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SMED 175 Podium: So with time dependent killing, you want to maximize the amount of time that the concentrations are above the the mic.
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SMED 175 Podium: Okay? And so with concentration, dependent killing. Do you remember there’s a long post antibiotic effect that happens. So even though the concentrations dip below the mic, the drug is still having its effect. Do you remember that concept? Okay.
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SMED 175 Podium: so beta lactams. They’re time dependent, and you want to maximize the time the drug concentrations are over that. And so that’s why.
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SMED 175 Podium: for really sick patients, you’ll give like continuous infusions of certain beta-lactam antibiotics to maximize that type.
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SMED 175 Podium: All right. I’m going to hand it over to Dr. Breams. Who’s going to do some really fun cases with you all.
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SMED 175 Podium: I will just say that this, that time dependent properties came up for me in clinic last week. Had a patient who
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SMED 175 Podium: has an infection in like a prosthetic joint. We’re trying to cure it, and there’s like a whole strategy towards this, but it involves kind of a consolidation period of oral antibiotics, and that’s the phase he’s in, and he tells us that he, instead of taking the Amoxicillin 3 times a day, he’s really only taking it twice, because the midday dose he just sort of forgets, or his wife isn’t there to give it to him. And so we had a whole conversation about? He’s asked, well, can I just
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SMED 175 Podium: do like one and a half in the morning and one and a half in the evening instead of 1? 3 times a day had a whole conversation about why, I know that doesn’t work. So let’s strategize on ways to get that midday dose to optimize the therapy for the consolidation. So it is clinically relevant.
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SMED 175 Podium: Yeah.
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SMED 175 Podium: I used to work at a sexual health clinic, and they started recommending, we prescribe an antibiotic to give patients that they take within 72 h of unprotected sex just the one time. How does that work with this time? Dependent schedule?
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SMED 175 Podium: So that would most likely be doxycycline and doxy, what we call doxypep, post-exposure prophylaxis. So which is really cool because we’re going to talk about those definitions again. So when we think about
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SMED 175 Podium: the what we’re trying to do with an antibiotic? We think about the pharmacology. Can the pharmacology get us what we’re trying to do? So in my case of a patient with a prosthetic joint infection, where there’s
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SMED 175 Podium: prosthesis and biofilm and a known bug and a known active infection, we want maximal efficacy. We want to maximize those pharmacokinetics when we’re talking about a post-exposure prophylaxis in the earliest phases before an infection gets established. You might not need the full breadth of the pharmacodynamics or pharmacokinetics of that drug. And doxycycline
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SMED 175 Podium: has different, not necessarily as time dependent, and has some amount of post antibiotic effect so in a post-exposure prophylaxis, we’re prophylacting. We’re not treating so the dosing is different.
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SMED 175 Podium: It’s a great point. So this is very clinically. This is a clinical case. That I will tell you straight out doesn’t have one right answer. So we get to just talk about it. And this is exactly what you will do in clinical environments, in picking antibiotics. So we got a 73 year old man. He’s brought to the local hospital emergency department by ambulance. His wife reports he had been his normal state of health until 3 days ago, when he developed a fever
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SMED 175 Podium: during the last 24 h. He’s complained of a painful right lower leg near the site of a recent traumatic cut, and his wife has noticed that he’s urinating more frequently and had one episode of incontinence. His wife reports that his medical history is significant. From mild, cognitive impairment and hypertension for which he takes Donepazil and Lisinopril. He’s allergic to Amoxicillin. She says he developed a rash many years ago, when he was prescribed Amoxicillin for bronchitis
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SMED 175 Podium: in the er he’s febrile hypotensive, Tachypneic and tachycardic meeting criteria for shock or sepsis he’s oriented only to person, does not answer your questions directly. His right lower leg does have a superficial wound with surrounding Erythema small amount of serous drainage, and he grimaces on palpation of the suprapubic area. And we’re going to get urinalysis and cultures. But we got to start antibiotics.
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SMED 175 Podium: and, as best we can tell, he might have a urine infection, he might have cellulitis.
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SMED 175 Podium: So what type of therapy are we using right now? So we need to pick therapy? What what category would we be in prophylactic, definitive, empiric, or preemptive
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SMED 175 Podium: empiric? Yes, so we see an infection. We see signs and symptoms of infection. We need to pick antibiotics, but we don’t know which bug we’re treating yet. So we’re empirically treating. And we’re looking for something that’s going to treat cellulitis and a uti. So how will we? How might we start to think through that?
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SMED 175 Podium: Any any thoughts?
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SMED 175 Podium: Remember, there’s no right answer. Just how do we think through this problem?
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SMED 175 Podium: What was that?
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SMED 175 Podium: It’s okay. Comical answers are allowed to. Yeah.
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SMED 175 Podium: we want an antibiotic that gets filtered into the kidneys. Okay, we’re going to want an antibiotic that gets to the kidneys. Very well, absolutely, because if he’s this sick from a urine infection, we would assume it’s like a pyelonephritis complicated. So we need to make sure the antibiotic is going to get to the kidneys. Yes.
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SMED 175 Podium: any other thoughts. Yeah, maybe we want something that does gram positive and negative. Since it’s probably different.
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SMED 175 Podium: Yeah. So we’re going to think about what are the most likely bugs causing these infections. So let’s think about cellulitis first.st What’s the most likely pathogens causing a cellulitis.
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SMED 175 Podium: I hear I’m hearing some
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SMED 175 Podium: staph and strep. Yep, gram positive staph and strep most common. Yep, all right. What about urinary tract infections. What’s the most common cause of a urinary tract? Infection?
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SMED 175 Podium: E. Coli, absolutely. And then maybe some protease in there, too. And we don’t really have any other big risk factors for complicated nosocomial hospital acquired stuff. So we need something that can treat staph and strep and E. Coli, and it’s going to have good penetration into the kidneys.
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SMED 175 Podium: Good! Are there any antibiotics that you can pull from your recent memory and your beta-lactams that might do that?
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SMED 175 Podium: We’ve got some cephalosporin suggestions here. Ceftriaxone, yeah. Yeah. Ceftriaxone has good gram positive coverage, gram-negative coverage. E coli. We mentioned it’s not specifically anti-staphylococcal for staph aureus but it does cover. It does have some coverage. So that wouldn’t be a terrible idea. Yeah.
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SMED 175 Podium: any other thoughts.
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SMED 175 Podium: Let me ask you this, we learned about some drugs in the uti session that we said probably we shouldn’t use for kidney involvement. Do you remember which ones those are that we would not want to use here
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SMED 175 Podium: because of the reasons we want to make sure it gets to the kidneys.
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SMED 175 Podium: Well, amino glycosides.
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SMED 175 Podium: we haven’t talked about those very much yet, and I wouldn’t want to use it because they’re terrible on the kidneys. But we’ll talk a lot about that later.
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SMED 175 Podium: But in the drugs, the urinary, the 1st line therapies for urinary tract infections. There’s a couple that we would not want to use because they don’t get to the kidneys.
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SMED 175 Podium: We also didn’t even mention them at all for staph and strep. So phosphomycin and nitrofurorantoin.
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SMED 175 Podium: those are those urinary drugs. But they don’t get to the kidneys. Very well.
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SMED 175 Podium: okay, but that’s exactly how you think about it? What bugs am I trying to treat here? What are the most likely pathogens? What’s the clinical scenario? Where do I need to make sure that tissue concentrations get to. So that’s great. Now, how would you say the history of the rash with Amoxicillin affects your antibiotic choice here
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SMED 175 Podium: shouldn’t affect your choice.
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SMED 175 Podium: That’s true, he said. Monobactams you could use, but it wouldn’t be enough to cover gram positives, and that is true. Would you give him Amoxicillin clabulanate which could cover staph strep, and some E coli.
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SMED 175 Podium: probably not with a history of rash, because then we just add rash on top of everything else. He’s got going on. Yeah, yeah. So we talked about beta-lactin cross allergies right? And this is a minor allergy rash. He didn’t have anaphylaxis. He didn’t have you know, immediate id hypersensitivity. So you might look at that chart and say, Okay, out here in these Cephalosporins
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SMED 175 Podium: those R side chains are different enough. I could probably safely use a cephalosporin here, despite the Amoxicillin history.
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SMED 175 Podium: Great.
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SMED 175 Podium: See? No right answer. But you guys did a lot of thinking. Good job.
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SMED 175 Podium: Okay, so we’ll just wrap up here with some practice questions. See how far we get. I have poll everywhere. Show hands. How many of you want to use poll everywhere, or want to, just like raise hands.
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SMED 175 Podium: pull everywhere.
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SMED 175 Podium: Everybody hates it. Cool. Okay.
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SMED 175 Podium: we’ll just talk it through that thing, too. All right. So we got a 45 year old man comes to the emergency department because of an infected wound on his left arm.
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SMED 175 Podium: Patient, says he accidentally placed his forearm on a hot stove about one week ago, resulting in the burn. Since then he’s been caring for the wounded home with a store, bought bandages and saline. He reports that he started experiencing pain in the region about 3 days ago, and when he changes the bandages he’s noticed a change in smell and color of the drainage on exam. He’s febrile and tachycardic looks unwell, and the culture of the wound has an oxidase positive gram-negative rod.
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SMED 175 Podium: Oh, that was gonna make me upset.
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SMED 175 Podium: Now, what? Oh, did it not launch? Okay, the question for you.
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SMED 175 Podium: Let me get this right. You guys have the slides.
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SMED 175 Podium: Which of the following would be the best antibiotic choice. Give me just a second. Let me fix this.
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SMED 175 Podium: You might need to talk to your friends 1st at your table to make sure you all understand what bug we’re talking about.
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SMED 175 Podium: I am logged in.
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SMED 175 Podium: Swear
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SMED 175 Podium: this is why we’re getting rid of pool everywhere. That’s weird, which yes is.
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SMED 175 Podium: I don’t know. I don’t know, either.
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SMED 175 Podium: Oh, maybe it’s my slideshow to show like this.
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SMED 175 Podium: Okay, cool. Thanks. Okay.
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SMED 175 Podium: Big talk thoughts on what is the pathogen?
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SMED 175 Podium: There’s multiple ways you could get to that knowledge of what you think the most likely pathogen is here.
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SMED 175 Podium: I tend for one. When I see oxidase positive, and they start describing lab stuff I’m like, oh, no, my brain hurts. I don’t want to think about that. So I go back to the clinical scenario like. Let’s say, we didn’t have any of that oxidase positive gram negative stuff that we had to really think hard about. What would we think about somebody with a burn, who is now getting an infection, and the odor is smelly, and maybe the color is strange. It would be nice if they told you it was maybe green in color.
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SMED 175 Podium: Viridans means green. So I could see how you could think that we’ll come back to that.
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SMED 175 Podium: Why, Pseudomonas
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SMED 175 Podium: cause Burns. So what does Pseudomonas cause? What does what types of infections do we know that Pseudomonas causes burn infections is a big one, the necrotic material that happens in a burn sets it up for pseudomonas. Especially. He’s been changing it. It’s wet environment, the saline, the wet dressing. So that just sets it up for pseudomonas from the environment and moisture.
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SMED 175 Podium: And so we know that Pseudomonas likes to do burn infections compared to regular old. Get a cut, and it’s staph and strep, because staph and strep live in on your skin. And it’s not necrotic material. It’s just, you know, an open wound which allows its way in. So in that environment it’s more likely staph and strep. Now, viridan strep is green wear.
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SMED 175 Podium: Where do we see the green of Viridan’s shrub?
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SMED 175 Podium: What does the green even refer to? How did it get its name? Viridan’s?
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SMED 175 Podium: How do we? How do we distinguish strep in the lab?
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SMED 175 Podium: What does it do in the culture? So we have. There’s strep. And then there’s
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SMED 175 Podium: 3 types of Hemolysis patterns, right? So there’s Alpha Beta and Gamma. So the Alpha hemolytic strep partially hemolytic it looks green, so it’s green because it looks green on an agar plate in the lab. Pseudomonas actually produces colors, so it’ll look green in the sputum. Somebody comes up it’ll look green on the bandages. It’ll actually look can look green in the environment because it produces these pigments as part of like its own defense strategy. Yeah.
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SMED 175 Podium: Yeah. Alpha, hemolytic. Yeah.
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SMED 175 Podium: And also strep viridins. We think about where where we find it. It’s in the mouth. We see it is cause of endocarditis. Not really the skin and soft tissue infections.
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SMED 175 Podium: Okay?
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SMED 175 Podium: All right. So then, what drug? We figured out the bug, 1st step.
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SMED 175 Podium: is this going to do the same thing to you, too. I don’t know what’s going on with pull everywhere, guys. So of the drugs that are listed there. Ceftriaxone.
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SMED 175 Podium: Nope, wrong slide. Thank you. Okay, we’ll just do it like that. Yeah. So Amoxicillin clavulanate ceftriaxone cefapem erdependum nafcillin
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SMED 175 Podium: show of hands for A, BC.
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SMED 175 Podium: D.
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SMED 175 Podium: Or E.
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SMED 175 Podium: Good job. See?
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SMED 175 Podium: C. Cefapem is anti-seudomonal. 4th generation cephalosporin erdapenem, and nobody got fooled by me there erdapenem nice broad spectrum carbapenem but it doesn’t treat pseudomonas it’s that one hole in the Carbapenem Swiss erdapenem. Good. Okay. What’s our next case?
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SMED 175 Podium: All right. 72 year old comes to the er with fevers and chills for 48 h. History of an aortic valvular disease had a prosthetic valve placed 5 years ago. Initial assessment unremarkable except for fevers and leukocytosis. However, on day 2, 4 out of 4 blood culture bottles were reported as positive and grow enterococcus fecalis tte is done and confirms aortic valve endocarditis.
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SMED 175 Podium: So I gave you the bug already, and I even gave you the diagnosis which should make it easier. So the question is, which of the following drugs
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SMED 175 Podium: would be should be included in this regimen. I’m not going to make you pick an entire complete regimen for this very complicated prosthetic valve endocarditis. But what are the following agents would be appropriate to include. So there’s ceftriaxone, meropenem, Astrianam, or ampicillin.
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SMED 175 Podium: How many for a Ceftriaxone, B Miro pennem c as Trianum or d ampicillin
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SMED 175 Podium: we got a table for ampicillin.
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SMED 175 Podium: So ampicillin is the right answer here. And enterococcus is one of those gram positives. It’s in the gram positive category. It’s technically kind of a streptococcus, but it doesn’t fall into
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SMED 175 Podium: the antibiotic susceptibilities neatly like the other streptococcus species. Do. Enterococcus is just naturally resistant. There’s not a lot of drugs that treat it among the beta-lactams, the ampicillin. This is the one where we said fecalis with the A for ampicillin, the ampicillin minopenicillins have good enterococcus coverage, whereas the other beta-lactams really don’t.
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SMED 175 Podium: It just has to do with the nature of its peptidoglycans, its transpeptidases. And Ampicillin now, I said trick question, because, interestingly, and when we talk about synergy with antibiotics, ampicillin and ceftriaxone can be synergistic for this particular disease, state endocarditis due to enterococcus
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SMED 175 Podium: that helps us get away from using other more toxic drugs. But Ampicillin would be a treatment a good one for Enterococcus. So Enterococcus is sort of like pseudomonas. You want to pay attention to what drugs treat it. Because there’s not a lot.
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SMED 175 Podium: Okay. Next one.
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SMED 175 Podium: guess what guys, we’re getting rid of pole everywhere. No more pull everywhere as of next year. It’s very exciting. Okay, regarding penicillins and cephalosporins, which of the following is the most accurate
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SMED 175 Podium: cleavage of the beta-lactam ring, will inactivate penicillins, but not cephalosporins.
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SMED 175 Podium: Penicillins act by inhibiting transpeptidases, but cephalosporins do not.
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SMED 175 Podium: Penicillin and cephalosporins. Are both bactericidal drugs penicillins. And cephalosporins. Are active against gram-positive cocci, but not gram-negative rods. Renal tubule damage is an important adverse effect, caused by both Penicillins and Cephalosporins.
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SMED 175 Podium: or none of the above.
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SMED 175 Podium: Oh, this one’s hard
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SMED 175 Podium: basically a true false for each one of those statements. So let’s say, cleavage of the beta-lactam ring will inactivate penicillins, but not Cephalosporins. Is that true or false.
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SMED 175 Podium: That’s false. So the beta-lactam ring so beta-lactamases can inactivate cephalosporins to Penicillins act by inhibiting transpeptidases, but cephalosporins, do not true or false
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SMED 175 Podium: do cephalosporins and penicillins have the same mechanism of action.
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SMED 175 Podium: Yeah, all beta-lactams. Yeah. So that statement is false. Penicillins and cephalosporins inhibit transpeptidases.
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SMED 175 Podium: Penicillins. And cephalosporins, are both bactericidal drugs.
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SMED 175 Podium: I think I wrote this question, and I would argue with myself. That’s like a mostly true, but not always so. They may not be bactericidal against every pathogen
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SMED 175 Podium: right? And not all penicillins are going to be bactericidal against something like Pseudomonas, for example.
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SMED 175 Podium: Penicillins and Cephalosporins are active against gram-positive cocci but not against gram negative rods, true or false.
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SMED 175 Podium: Yeah, that’s a global statement. That’s false. Right? So, penicillin, some penicillins have broad activity against gram positives and gram negatives, same with cephalosporins, renal tubule damage, important adverse effect caused by both penicillins and cephalosporins.
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SMED 175 Podium: True or false.
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SMED 175 Podium: it was a kidney kidney on the sketchy video
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SMED 175 Podium: that one I would say the renal tubular damage is more of an issue with the penicillin. So when we talk about adverse effects as a group for the Penicillins, that 1st column of the Beta-lactams. The renal tubular toxicity is much more of a problem there. So the most accurate is probably the bactericidal. But just to be aware that it’s not for every single bug.
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SMED 175 Podium: So they’re bactericidal for the bugs that each one covers, but not necessarily for all bugs.
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SMED 175 Podium: Bad question. I will not ask you a question like that on an exam.
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SMED 175 Podium: Okay, what time are we at? We are at time? I can post answers these other questions just for your practice. I can post the answers later if you want. And if you have additional questions, feel free to email all of us, any of us.
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SMED 175 Podium: and if this kind of stuff is helpful, I think, let assessment know for the next. Go round on Consolidation weeks.
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SMED 175 Podium: and then you can let us know what you’d like like us to cover.
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SMED 175 Podium: Okay
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SMED 175 Podium: of your day.
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Skye McKennon (she/her): Bye, thanks for joining
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SMED 175 Podium: Go enjoy the sunshine. Thank you for being here on such a beautiful sunny day.
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Skye McKennon (she/her): I hope you feel better, Connie. By the way.
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SMED 175 Podium: Oh, thank you, Skye.
- This page was last updated on March 26, 2025.