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Cephalosporins – Cell Wall Synthesis Inhibitors (Antibiotics)

by Pravin Shukle, MD

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    00:01 Next we have the cephalosporins.

    00:03 The cephalosporins are divided into generations.

    00:06 Let's start with the first generation cephalosporins.

    00:10 The most commonly used is Cefazolin.

    00:13 Cefazolin has excellent coverage against gram positive organisms.

    00:17 And if you think about it, it's an excellent antibiotic to use in surgical infections.

    00:22 Now, if you have a skin infection, Cefazolin is probably your go to drug.

    00:28 However, cefazolin does not have much effectiveness against gram-negative bacteria.

    00:33 So for example, if you had a urinary tract infection, cefazolin is not going to be very intelligent choice.

    00:40 Okay, I had said before that the first generation cephalosporins had excellent gram-positive coverage, but not so great gram-negative coverage.

    00:50 As we move down in the generations, you'll start to see that the higher generation medications have better and better coverage for gram-negative organisms.

    00:59 Now, those gram-negative organisms can be seen in respiratory tract infections.

    01:04 We often think of as a second-generation cephalosporins as being respiratory drugs.

    01:09 Why is that? Because for upper respiratory infections have a lot of gram-positive organisms and some gram-negative organisms.

    01:17 For example, cefuroxime works against gram-negative bacteria quite nicely, and it works very well against Haemophilus influenza.

    01:25 So if we have a person who has either a strep infection or Haemophilus infection, but we don't know, will often use cefuroxime.

    01:34 Now, the nice thing about cefuroxime and these drugs is that they also have a little bit of anaerobic activity.

    01:42 Generally speaking, we don't see anaerobic activity much in the lung.

    01:48 Now we move on to the third generation cephalosporins.

    01:50 So what do you think based on my logic that these are going to cover? Well, you'd be right.

    01:56 These drugs like cefotaxime, are very effective at gram-negative organisms.

    02:02 Unfortunately, you make a trade off because they're less effective at gram-positive organisms.

    02:07 They will often work against organisms that are resistant to many penicillins.

    02:14 So sometimes we'll either use it as an agent that we know a person has had a penicillin before and didn't respond.

    02:22 Now, we only use this particular type of cephalosporin and serious infections.

    02:27 I like to say that these are intensive care unit drugs, but not really.

    02:31 I would say that they're ward at drugs.

    02:33 So we tend to use them on the medical floor when people have really bad infections.

    02:39 Let's move on to the fourth generation cephalosporins.

    02:42 This category involves a very complicated drugs Cefepime is a perfect example of that.

    02:50 Now, these drugs are zwitterions.

    02:53 What's a zwitterion? A zwitterion is an ion or a drug that has two different charges on the same molecule.

    03:01 Normally, we think of molecules as either being positively charged or negatively charged, A zwitterion has a positive charge on one end and the negative charge on another.

    03:10 Okay, let's move on.

    03:12 So a fourth generation cephalosporin like cefapime is more resistant to beta lactamase producing organisms.

    03:20 Enterobacter is a particularly difficult infection to treat.

    03:25 We often see this in very sick patients who are in the intensive care unit or on the ward.

    03:33 This drug is often used in infections that are caused by MR Resistant staphylococci.

    03:39 So, let's say a person comes in.

    03:41 They have a methicillin-resistant staphylococci.

    03:44 You suspect that they have a beta-lactamase based infection.

    03:48 Cefepime is a really good choice in this particular type of patient.

    03:53 Now we move on to fifth generation cephalosporins.

    03:56 It includes drugs like ceftaroline.

    03:59 Now, I want to make a mention that not everyone accepts the whole nomenclature behind fifth generation cephalosporins.

    04:06 There are some people who just say that all fifth generations are unclassified.

    04:10 I'll leave that debate alone for a moment.

    04:13 Now take a look at this structure. It's a very complicated structure.

    04:16 So you can see, that these fifth generation cephalosporins are larger, more complicated molecules.

    04:23 Ceftaroline, has excellent MRSA coverage, and we will often use it in patients who are sick with MRSA.

    04:31 This is another agent.

    04:32 You can see it's a slightly simpler structure.

    04:36 It has powerful antipseudomonas activity, and it also can work against VRE, which stands for Vancomycin-resistant Enterococcus.

    04:45 Ceftolozane is another fifth generation cephalosporin.

    04:50 We will often use this in intraabdominal infections that are complicated.

    04:54 So intra abdominal infections tend to have a lot of gram-negative organisms.

    04:59 They sometimes have gram-positive organisms.

    05:02 And more importantly, they have anaerobic organisms.

    05:06 And treating anaerobic organisms is notoriously difficult.

    05:09 We have to resort to very complicated drugs.

    05:12 This is an excellent choice for an abdominal infection.

    05:16 Sometimes complicated urinary tract infections can be treated with this drug as well.

    05:21 And when you think about it, urinary tract infections also tend to have a lot of gram-negative.

    05:27 Sometimes they'll have anaerobic.

    05:29 and sometimes they'll have Pseudomonas infections.

    05:32 We will often combine it with tazobactam.

    05:35 And remember that tazobactam is combined with other agents to like Piperacillin.

    05:40 Finally we have the unclassified.

    05:42 Now, maybe someday we'll call this the sixth generation. I don't know.

    05:46 There's a whole host of them.

    05:48 They haven't really been studied very much.

    05:50 They're brand new.

    05:51 And information will come out as they start to get more and more clinical usage.


    About the Lecture

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

    • Cephalosporins
    • Other Beta-Lactam Drugs

    Included Quiz Questions

    1. Gram-negative bacteria
    2. Gram-positive bacteria
    3. Intracellular bacteria
    4. Bacterial infections of the brain and spinal cord
    5. Beta-lactamase-producing bacteria
    1. Ceftaroline
    2. Cefotaxime
    3. Cefazolin
    4. Cefotetan
    5. Ceftriaxone

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

     Pravin Shukle, MD

    Pravin Shukle, MD


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    pleaaaase add more questions to each chapter
    By RK N. on 22. July 2017 for Cephalosporins – Cell Wall Synthesis Inhibitors (Antibiotics)

    I loved the lecture so much! But sir, isn't there something called as fifth generation cephalosporins? And please please pleaaaase add more questions to each chapter. Only 3 questions per chapter is not enough. Please consider this sir.