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Penicillins – Cell Wall Synthesis Inhibitors (Antibiotics)

by Pravin Shukle, MD
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    00:00 Let's start off with the penicillins.

    00:03 So remember that penicillins are active on the cell wall.

    00:07 Now the cell walls you can see them here.

    00:10 They have sites that are amenable to transpeptidation.

    00:14 This allows cross-linking of the components of the wall.

    00:18 And when you have cross-linking you have a stronger wall.

    00:22 Now cross-linking is created or facilitated by proteins that act on those peptidoglycans of the cell wall and links them together.

    00:31 Much like a zipper does.

    00:32 Penicillins have a beta lactam ring that binds to that protein.

    00:38 And for this reason the proteins are called penicillin binding proteins.

    00:43 So penicillin binding protein is where the penicillin is going to be active.

    00:48 Now if you inhibit the penicillin binding protein, autocatalysis of the cell wall will occur and the cell wall will break down.

    00:57 Now, the bacteria have developed defense mechanisms against the penicillins.

    01:04 So some bacteria have beta lactamase enzymes.

    01:08 They're also called penicillinases in other parts of the world.

    01:12 Now these beta lactamase break down that beta lactam ring.

    01:16 This is the mechanism of most types of resistance.

    01:19 And they're countered by the inhibitors of these enzymes.

    01:23 So clavulanic acid is an agent that inhibits the beta lactamase.

    01:28 Now we use that in combination with amoxicillin.

    01:31 And we sell it as a amoxicillin clavulanate.

    01:34 Sub lactam is another beta lactamase and we sometimes combine that particular agent with ampicillin and we sell ampicillin sublactam.

    01:45 And tazobactam is the third one and for example, they'll combine with piperacillin as peptazo.

    01:54 Now there are other mechanisms of resistance that bacteria will have against penicillin.

    02:00 Sometimes there is actually a structural change in the penicillin binding protein which renders immunity or resistance to penicillins.

    02:08 This is actually the mechanism of methicillin resistance.

    02:12 And it's become a real problem in our hospitals.

    02:15 Sometimes there's actually a change in the porin structure of the outer wall.

    02:20 So for example resistance of pseudomonas to penicillins is a great example.

    02:25 The penicillin isn't able to penetrate because there is a change in the porin.

    02:30 Now we'll talk about some narrow spectrum penicillins that are out there.

    02:36 Methicillin, naficillin and oxacillin are narrow spectrum agents.

    02:42 They are not used much anymore.

    02:43 I remember when we started medicine, we used to use methicillin all the time.

    02:48 Methicillin resistant staphylococcus is essentially taken methicillin of the table in terms of our choice.

    02:54 Because these MRSA's are resistant to all penicillins.

    02:59 Methicillin is also linked to interstitial nephritits.

    03:04 Naficillin is associated with neutropenia.

    03:07 So these agents are falling out of favor.

    03:09 But they still do show up on our susceptibility charts.

    03:12 Now ampicillin and amoxicillin, you probably quite familiar with.

    03:18 In fact I would bet that some of you have been on these medications yourselves.

    03:22 These are wide spectrum agents.

    03:24 But they are still susceptible to beta lactamases.

    03:28 They are enhanced when combined with clavulanate.

    03:31 And enterococcal infections, ampicillin is complementary with aminoglycosides.

    03:38 So in enterococcal infections, we'll often use combinations like ampicillin and gentamicin.

    03:43 Because they work very well together.

    03:45 That's called bacterial synergy.

    03:47 And I'm going to mention it again when I talk about gentamicin.

    03:51 Piperacillin and ticarcillin are stronger agents.

    03:56 These are very strong agents against gram negative organisms.

    04:01 And once again they are very complimentary with aminoglycosides.

    04:05 So piperacillin for example will be combined with tobramicin to give a very strong gram negative treatment.

    04:11 Once again these drugs are susceptible to the penicillinases.

    04:16 So we often combine drugs like piperacillin with tazobactam to limit the resistance.


    About the Lecture

    The lecture Penicillins – Cell Wall Synthesis Inhibitors (Antibiotics) by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.


    Included Quiz Questions

    1. Piperacillin
    2. Ampicillin
    3. Amoxicillin
    4. Methicillin
    5. Nafcillin
    1. Transpeptidation to form crosslinking.
    2. Glycosylation to form polymers.
    3. Hydrolysis to form monomers.
    4. Nucleophilic attack to form polymers.
    5. Production of free radicals.
    1. TIcarcillin is contraindicated with administration of aminoglycosides.
    2. Methicillin is associated with interstital nephritis.
    3. Nafcillin is associated with neutropenia.
    4. Ampicillin is a wide spectrum antibiotic that is susceptible to beta lactamases.
    5. Oxacillin is a narrow spectrum penicillin.
    1. Structural changes in penicillin binding protein rendering immunity to penicillins.
    2. Elevated internal pH neutralizes penicillin.
    3. Beta lactamases break down the beta lactam ring of penicillins rendering them inactive.
    4. Bacteria have developed enzymes that glycosylate penicillin to neutralize it.
    5. Bacteria have developed cell wall materials with extreme positive charges to repel penicillin.

    Author of lecture Penicillins – Cell Wall Synthesis Inhibitors (Antibiotics)

     Pravin Shukle, MD

    Pravin Shukle, MD


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