Cephalosporins Explained Clearly Transcript
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“Welcome to another MedCram Lecture! We’re going to talk about Cephalosporins and specifically, the different generations of Cephalosporins, some representative antibiotics in each class and what are the unique things about those generations and what they do in their coverage.
There are 5 generations of Cephalosporins. We’ve got the 1st generation of Cephalosporins, we’ve got the 2nd – which we’ll talk about – the 3rd – which is the workhorse of the pneumonia scene – we’ve got the 4th generation – which has got the Pseudomonas coverage – and then finally the 5th, which is an interesting generation that we’ll talk about.
As we go from first, to second, to third, to fourth, you’ll see that there is better and better Gram negative coverage, so at the very beginning, with 1st generation Cephalosporins, we have medications like Cefazolin and Cefalexin and these antibiotics really have no anaerobic coverage, but what they did have a lot of coverage for is Gram positives. This is going to be our Gram positive box and this is going to be our Gram negative box. In terms of Gram positives, it has really good Staph and actually pretty good Strep coverage. Where do we see these things being used? We see these things being used in, for instance, skin infections, because this has really good Gram positive coverage; no anaerobic coverage, good Staph and Strep, and in terms of Gram negative, it would still take care of regular Gram negative, like E. coli, Proteus and Klebsiella.
When they went on to the 2nd generation of Cephalosporins, here we’re talking about medications like Cefuroxine and like Cefotetan. The biggest thing about this was that now, we had anaerobic coverage. That was the big thing, and as a result of that, we’re now looking at intra-abdominal. The reason why we could do that was because there’s a lot of anaerobic bacteria intra-abdominally, but in terms of the Staph and Strep, it stayed the same; going from the 1st generation to the 2nd, there was really no change. We didn’t lose much in terms of Staph and Strep, but going from 1st generation to 2nd generation, we actually got a little bit better Gram negative coverage. That’s what made it really well in terms of intra-abdominal infections – the 2nd generation was better in terms of that.
Let’s go on to the 3rd generation. 3rd generation Cephalosporins – there’s three major examples and you should know these. One of them is Ceftriaxone, the other one is Cefotaxine and the last one is a very important one called Ceftazidine. In terms of anaerobic coverage, it lost it again; no anaerobic coverage here, whereas we had it back in the 2nd generation. In terms of Gram positives here, it was okay, definitely very good in Pneumococcus. In terms of Staph, probably not as good a coverage in terms of Staph Aureus. Because it has good Pneumococcal coverage, 3rd generation Cephalosporins were really good at lung infections, so we’re talking about community-acquired pneumonia. There’s a couple of things I should mention here and that’s very specifically, that Ceftazidine is covering Pseudomonas. That’s an important thing we’re going to have to bring up, here where we talked about Gram negatives, is that here, it’s even better. You can see as we go up the list in terms of generations, that the Gram negative coverage keeps getting better; specifically, if you’re using Ceftazidime, you can now cover Pseudomonas. Even if you are not, we are talking good coverage with Neisseria Gonorrhoeae, we’re talking about Enterobacter, we’re talking about Seratia. Here’s the big one: if you use Ceftazidime, it will cover Pseudomonas. That’s a big one because Pseudomonas is the infection that people get in nursing homes, specifically in their lung. So, that’s 3rd generation, probably one of the best up to that point in terms of Gram negative coverage.
Now, 4th generation – the big one you got to know there is Cefepime. Cefepime is important because it also covers the big P, the big Pseudomonas. In terms of anaerobic coverage, still no anaerobic coverage. So far, the only one that covers anaerobs is the 2nd generation Cephalosporins. The 4th generation of Cephalosporins were something quite amazing because what it did is it took the strength of the 1st generation for Gram positives – really strong – and it added the great Gram negative coverage of the third and made it strong. Cefepime is really outstanding. So, what are we using these for? We are using these for very serious infections anywhere, because it’s got excellent coverage, strong Gram positive, strong Gram negative, and extra bonus is it covers Pseudomonas. We can think of, for instance, immunocompromised patients, of fever of unknown origin. This 4th generation of Cephalosporins had excellent, excellent coverage.
When we go to the 5th generation of Cephalosporins, the 5th generation is kind of unusual because we’ve got different players in that generation, which are very, very different from each other. The first one that I want to talk to you about is Ceftolozane. It actually is combined with Tazobactam, which is a beta-lactamase inhibitor. The other one is Ceftraroline. These are very different 5th generation Cephalosporins. Again, for the second time, we have good anaerobic coverage. You should know that the 2nd and the 5th generation have anaerobic coverage. Let’s talk about these two players. Ceftolozane/Tazobactam – what they did, they took Ceftazidime, that structure, and they basically made it better and this is the most potent anti-Pseudomonal Cephalosporin that we currently have. They added on Tazobactam, which is a beta-lactamase inhibitor. This is a super-anti-Pseudomonal that works well.
Just to review, we’ve got three Cephalosporins that have anti-Pseudomonal coverage and I think that’s important to know – Ceftazidime, Cefepime and Ceftolazene. We use Ceftriaxone as our 3rd generation Cephalosporin to treat community-acquired pneumonia. Notice that Ceftriaxone, or Rocephin, does not have any anti-Pseudomonal coverage. So, if a patient is coming in from a nursing home or some institution or a hospital, they are at risk for having Pseudomonas; you should not use Ceftriaxone. Do not use Ceftriaxone because Ceftriaxone has no anti-Pseudomonal coverage. The only one that has anti-Pseudomonal coverage is Ceftazidime, Cefepime and Ceftolazene. This is a great anti-Pseudomonal medication.
What is Ceftaroline? What is so good about it? Ceftaroline – Teflaro is the trade name – actually covers MRSA. It is the only Cephalosporin that can actually treat MRSA. That’s pretty important. It’s currently indicated for skin and soft tissue infections and also community-acquired pneumonia. It has not, as of this tapping, gotten the FDA approval for MRSA pneumonia.
One other bit of advice information I want to give you is sometimes, when they are actually testing bacteria, like Gram negatives, for Cefepime, they’ll notice that it is sensitive to Cefepime, but it’s not sensitive to any other Cephalosporin. This you should think about in terms of, if it is possible, to be an extended-spectrum beta-lactamase. If they are, you should not use any Cephalosporins, whatsoever, and to switch to Monobactam and we’ll talk about that in one of our next lectures.
Just to review here again, we’ve got the 1st, 2nd, 3rd, 4th and 5th generation. The 1st generation was really good on Gram positives, Staph and Strep, did not have anaerobic coverage and had so-and-so Gram negative coverage; really good for skin infections like Cefazoline, Cefalexin. Because it had good Gram negative coverage like E. coli, you could use it in simple urinary tract infections.
Going to 2nd generation, we’ve got anaerobic coverage, we’ve got better Gram negative coverage; this is intra-abdominal because of that anaerobic and that better Gram negative coverage.
3rd generation is the workhorse for community-acquired pneumonia, because of the Ceftriaxone, but you should also know that it also holds Ceftazidine, which is an anti-Pseudomonal and it’s got one of the best Gram negative coverage out of all of the generations.
4th generation took the best of both worlds. It took the 1st generation Gram positive coverage and it took the 3rd generation Gram negative coverage, put it all together and you got Cefepime, which is anti-Pseudomonal, for serious infections where you need broad-spectrum antibiotics.
Finally, the 5th generation has two odd players that are really different from each other. Ceftolozane, which is the anti-Pseudomonal, which you have to worry about in hospital-acquired infections, but also, coverage with Ceftaroline, also something you have to worry about in hospital-acquired infections – two different drugs, same generation.
Thanks for joining us!”