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Linezolid, Streptogramins and Chloramphenicol – Bacterial Protein Synthesis Inhibitors (Antibiotics)

by Pravin Shukle, MD
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    00:00 So let's talk about that last one, linezolid.

    00:04 It's a new class of antibiotics.

    00:06 And they're used in drug resistant gram positive cocci infections like Methicillin-resistant Staphylococcus aureus, penciling-resistant Streptococcus pneumoniae, and vancomycin-resistant entrococcus.

    00:19 They bind to their 50 S ribosomal subunit as I had mentioned before.

    00:23 There's no cross resistance with other protein synthesis inhibitors.

    00:27 An they're reserved for multi-drug resistant agents.

    00:30 In our facilities we actually restrict the use of this medication to infectious disease specialists.

    00:37 Now, I want to just show you a picture from an electro-cardiogram.

    00:41 This is a tricuspid valve.

    00:43 So on the left side you can see tricuspid valve but you can't really see any kind of vegetation.

    00:50 On the right where the green arrow is pointing, you can see a large vegetation on of the tricuspid valves.

    00:56 This person has obviously, a fairly severe endocarditis.

    01:02 And valvular vegetation because it's the tricuspid valve.

    01:06 You know it's the right side, it's probably involved with some kind of intravenous drug abuse.

    01:10 This patient had multiple resistant infection, was actually treated quite successfully with this drug.

    01:16 Now in terms of toxicity, toxicity of this drug include thrombocytopenia and neutopenia.

    01:22 This particular patient developed thrombocytopenia which was managed conservatively.

    01:28 Unfortunately you can have serotonin syndrome.

    01:32 So remember that if you know, your IV drug abusers also tend to be on antidepressants.

    01:37 There is a high correlation there.

    01:39 And if you're using this antibacterial agent you may actually induce a serotonin syndrome.

    01:43 So please go back to your psychiatry lectures and take a good look at serotonin syndrome so that you understand it.

    01:49 The streptogramins are a combination of two medications.

    01:56 They tend to be bactericidal with really good post antibiotic effects.

    02:01 They are active against MRSA, VRSA and other resistant enterococci.

    02:06 Now, enterococcus faecalis is resistant to these agents because they have a very unique efflux transport mechanism which is kind of cool.

    02:18 These organisms have actually evolved of way of getting rid of streptogramins from the inside of their cytoplasm.

    02:24 In terms of toxicity and adverse events, they are -- you often get a very painful injection sight.

    02:31 You can get myalgia and arthralgia.

    02:33 Remember that these agents are potent inhibitors of cytochrome 3A4.

    02:38 So therefore if you remember your other lectures, they will increase plasma levels of drugs like cyclosporine, diazepam and warfarin.

    02:47 Chloramphenicol has a very distinct structure.

    02:52 There's actually no other drug in it's class.

    02:54 So it's on it's own.

    02:55 It has wide distribution.

    02:57 It has a polar molecule as you can see.

    02:59 So it crosses the blood brain barrier and the blood uterine barrier.

    03:04 It is inactivated in the liver and has minimal renal excretion.

    03:08 It's bacteriostatic against Haemophillus, Neisseria, Bacterioides species.

    03:14 It's also used as a backup drug against Salmonella, pneumococcal disease and meningococcus.

    03:19 It can also be used topically quite often as well.

    03:22 It it not active against chlamydia species.

    03:25 The resistance is through a plasmid mediated formation of an enzyme called acetyltransferase that inactivates that drug.

    03:34 The toxicity, specially for topical use is direct irritation.

    03:39 You can also get superinfections like candidiasis.

    03:42 Remember that chlromaphenicol does not work against candida.

    03:46 Aplastic anemia is potential side effect that's relatively rare about 2.5 per 100,000.

    03:54 It is irreversible and can be fatal though.

    03:57 The one thing that I want you to remember about chloramphenicol is something called Gray Baby syndrome.

    04:03 It is going to be on your exams at some point in your career.

    04:06 That is where you get anemia, cyanosis, cardiovascular collapse.

    04:11 It effects neonates specially those who are premature.

    04:15 And it maybe linked to deficiency in the hepatic glucoronyltrasferase.

    04:20 So it's something to be aware of and to know.


    About the Lecture

    The lecture Linezolid, Streptogramins and Chloramphenicol – Bacterial Protein Synthesis Inhibitors (Antibiotics) by Pravin Shukle, MD is from the course Antimicrobial Pharmacology. It contains the following chapters:

    • Linezolid
    • Streptogramins
    • Chloramphenicol

    Included Quiz Questions

    1. Chloramphenicol resistance is due to plasmid-mediated formation of the enzyme acetyltransferase, which inactivates the drug.
    2. Linezolid resistance organisms use an efflux transport mechanism.
    3. Chloramphenicol is active against chlamydia.
    4. Streptogramins are active against E. faecalis.
    5. Chloramphenicol is active against drug resistant gram positive cocci.
    1. It is a potent inhibitor of CYP450 3A4.
    2. There is no cross resistance with other protein synthesis inhibitors.
    3. When combined with SSRIs it may lead to serotonin syndrome.
    4. It is associated with thrombocytopenia and neutropenia.
    5. It may be used against MRSA and VRE.
    1. It is the result of Streptogramin toxicity.
    2. It may be linked to a deficiency in hepatic glucuronyltransferases.
    3. It primarily affects newborns, especially premature newborns.
    4. It presents with anemia, cyanosis and cardiovascular collapse.

    Author of lecture Linezolid, Streptogramins and Chloramphenicol – Bacterial Protein Synthesis Inhibitors (Antibiotics)

     Pravin Shukle, MD

    Pravin Shukle, MD


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