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Monobactams, Cyclic Lipopeptide and Polypeptide – Cell Wall Synthesis Inhibitors (Antibiotics)

by Pravin Shukle, MD

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    00:01 Cell wall synthesis inhibitors also include a broad spectrum of other agents, one of them are the monobactams.

    00:08 Now monobactams include drugs like aztreonam.

    00:11 Aztreonam has some adverse effect associated with it including GI upset and vertigo and headache, but the reason why we really like this particular agent is that it doesn't have any cross allergy with penicillins so when you have a patient come in who would really benefit from a penicillin but is allergic to penicillins we can use aztreonam.

    00:33 The next category are cyclic lipopeptides.

    00:36 Lipopeptides are very, very, complicated structures you can see here how complicated it really is.

    00:42 Daptomycin is the prototypical agent in this drug class.

    00:46 It is what we define as a cyclic lipopeptide.

    00:50 It is for the treatment often used in VRE which is vancomycin resistant enterococci and VRSA which is vancomycin resistance staph aureus.

    01:00 We sometimes have to monitor a person's creatinine kinase after we administer this agent because it can be very myopathic.

    01:08 So remember, on your exam, daptomycin is myopathic.

    01:13 You have to watch that very closely on your exams.

    01:16 I wanna give another drug that is myopathic and that is the statins.

    01:20 So cholesterol treating agents like Crestor or resuvastatin are myopathic as well.

    01:28 When you have a multiple choice question you will sometimes be given daptomycin and statin together and you have to pick out which of the agents are myopathic so just a little off the cuff help on your exams that are coming up.

    01:44 Daptomycin have some GI offense as well so you can get GI upset a lot of upset stomach.

    01:50 People will get vertigo and headache from this particular agent.

    01:54 Again, the nice things about these miscellaneous agents is that there isn't a cross reactivity in terms of patients who are penicillin allergic.

    02:02 Daptomycin is kind of a fun agent to see how it works.

    02:06 Daptomycin is this complex molecule with the stringy end that inserts into the cell wall.

    02:13 Now it's complicated and it's huge as that molecule is it's not done because now it'll bind to a whole bunch of other daptomycin molecules and it will form something called oligomers or oligomerization.

    02:25 Oligomers are when you have one drug binding to itself multiple times to form a complex.

    02:31 This complex becomes a channel in the wall of the bacteria.

    02:36 What happens with this channel is it get ion efflux.

    02:40 That ion efflux causes a depolarization of the membrane.

    02:45 Why do you care if the membrane is depolarized? Because if a bacterial membrane is depolarized, DNA and RNA synthesis cannot start or cannot proceed and that means that protein synthesis also can't proceed which means that the cell stops producing those proteins that are necessary for life the cell stops, the bacteria stops.

    03:11 Let's move on to a different class called the cyclic polypeptides.

    03:15 Cyclic polypeptides are also very complicated.

    03:19 They are locally effective and they are often are limited to topical use.

    03:23 Topical doesn't just mean the skin because in this particular case we'll use this agent in sore throats.

    03:29 We'll often will spray at the back of the throat if a person has an infection in the back of the throat only and it'll act locally to affect exchange.

    03:38 Now, people like me love these kinds of drug not because they are particularly useful in the clinic but because they are so complicated and they are fun to look at.

    03:47 Now this drug will inhibit protein biosynthesis of gram-positive organisms.

    03:51 If you think about that, that's mostly the upper respiratory track, isn't it? They are also and this is important, completely ineffective against gram negative organisms so if you suspect a patient having a gram negative organism as a cause of the infection, don't use this particular agent.

    04:11 We also have some glycopeptide antibiotics.

    04:13 The most commonly known of the glycopeptide type antibiotic is vancomycin and I've mention it in some of my other lectures.

    04:21 Vancomycin is a bacterial glycoprotein. It binds to the peptidoglycan in the cell wall itself.

    04:30 It binds to the alanine terminal and it acts as a stop function in cell wall synthesis.

    04:36 One of the downsides of this particular agent is that if the agent has an altered alanine terminal on its NAG, it will not allow vancomycin to bind therefore in this particular bacteria who have a decreased affinity for vancomycin, they tend to be vancomycin resistant.

    04:57 Now, vancomycin is limited to serious infections only.

    05:01 It's a very powerful agent.

    05:03 It has some side effects that I'll mention later and it's a large molecule.

    05:07 Because it's such a large molecule it does not cross the blood brain barrier very well.

    05:13 It is often used intrathecally in certain serious spinal infection so people with really severe spinal or central meningitis or spinal meningitis.

    05:24 We -- and they're resistant to therapy and they are really, really, sick we can actually inject it directly into the spine in a buffered solution and treat the infection quite well.

    05:37 Now, we can use this drug orally but as I said before it doesn't really cross the blood brain barrier and it also doesn't cross the gut barrier either.

    05:46 It stays in the gut so it makes sense that the only place we're gonna use it as an oral agent is in infections of the gut itself.

    05:55 An example is an enterococcus-mediated infection.

    05:58 Now one of the downsides is that we are now starting to see vancomycin resistant enterococci.

    06:04 Vancomycin has some toxicity issues.

    06:07 You can get something called red man syndrome and I want you to remember this, rather sexist term, it is always on exams.

    06:15 I am gonna guarantee you that it's gonna be on your test.

    06:18 Doesn't matter if you are writing your USMLE or if you are writing an infectious disease exam, red man syndrome on your exam, vancomycin.

    06:27 Red man syndrome is essentially a severe cutaneous reaction where you have tremendous flushing.

    06:33 People turn a bright red and its often because of histamine release.

    06:37 You will also get other side effects from this medication including phlebitis, ototoxicity, and some nephrotoxicity as well.

    06:44 Teicoplanin is another drug in this drug class.

    06:48 Teicoplanin is even more complicated than vancomycin in structure and in fact when you take a look at the structure here on the slide, you will see that there's a red R way up in the corner, that R can be many different groups.

    07:02 It could be a whole chain of structures so it's not just what you are seeing on the screen here today it's actually a much more complicated molecule than what I'm showing you.

    07:13 Now, teicoplanin is used in prophylaxis it's not really used in a lot of clinical practice.

    07:19 It's used for treatment of methicillin-resistant staph aureus and methicillin-resistant enterococcus faecalis.

    07:27 It's also used for the treatment of pseudomembranous colitis and in clostridium difficile diarrhea.

    07:35 Alright, we're almost done. I have one more to show you.

    07:39 Let's take a look at this drug, this is called bacitracin.

    07:42 Bacitracin is very commonly used in the prevention of certain types of infections and we often will use it as a prophylactic measure on the wards.

    07:50 It's a bacterophenol inhibitor.

    07:52 It's used in the topical treatment so topical treatment of certain types of infections and it's used in decontamination syndromes.

    08:01 It's used in staph colonization of the skin so sometimes you'll see dermatologists using it for particularly bad superficial infections.

    08:12 One of the problems with bacitracin taken intravenously or parentally is that it causes nephrotoxicity and because of that and because we have other agents that can do the job just as well, we tend not to use it intravenously or what we call parentally.

    08:30 We'd prefer instead just to use it on the surface of the skin and you'll see it often used on the wards when you have an MRSA outbreak.

    08:39 Okay, that's it. Well done. Good luck on your exams, you're gonna do well.


    About the Lecture

    The lecture Monobactams, Cyclic Lipopeptide and Polypeptide – Cell Wall Synthesis Inhibitors (Antibiotics) by Pravin Shukle, MD is from the course Antimicrobial Pharmacology. It contains the following chapters:

    • Vancomycin
    • Bacitracin
    • Daptomycin

    Included Quiz Questions

    1. It is markedly nephrotoxic when taken parenterally.
    2. Enzymes in the blood break it down before reaching its target.
    3. It causes severely elevated levels of creatinine kinase.
    4. It requires oxygen to be active as a bactericidal agent.
    5. It results in severe histamine release leading to “red man syndrome”.
    1. Vertigo
    2. Phlebitis
    3. Severe histamine release
    4. Nephrotoxicity
    5. Ototoxicity
    1. Intrathecally
    2. Intravenously
    3. Intramuscularly
    4. Rectally
    5. Orally
    1. Creatine kinase
    2. Creatinine and BUN
    3. White blood cell count
    4. Iron studies
    5. Transaminases

    Author of lecture Monobactams, Cyclic Lipopeptide and Polypeptide – Cell Wall Synthesis Inhibitors (Antibiotics)

     Pravin Shukle, MD

    Pravin Shukle, MD


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