Cephalosporins – Cell Wall Synthesis Inhibitors (Antibiotics)

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 empiric antibiotic choice.

00:41 Okay, I had said before that the first generation cephalosporins had excellent gram-positive coverage, but not so great gram-negative coverage.

00:51 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.

01:00 Now, those gram-negative organisms can be seen in respiratory tract infections.

01:05 We often think of as a second-generation cephalosporins as being respiratory drugs.

01:10 Why is that? Because for upper respiratory infections have a lot of gram-positive organisms and some gram-negative organisms.

01:18 For example, cefuroxime works against gram-negative bacteria quite nicely, and it works very well against Haemophilus influenza.

01:26 So if we have a person who has either a strep infection or Haemophilus infection, but we don't know, will often use cefuroxime.

01:35 Now, the nice thing about cefuroxime and these drugs is that they also have a little bit of anaerobic activity.

01:43 Generally speaking, we don't see anaerobic activity much in the lung.

01:49 Now we move on to the third generation cephalosporins.

01:52 So what do you think based on my logic that these are going to cover? Well, you'd be right.

01:57 These drugs like cefotaxime, are very effective at gram-negative organisms.

02:03 Unfortunately, you make a trade off because they're less effective at gram-positive organisms.

02:08 They will often work against organisms that are resistant to many penicillins.

02:15 So sometimes we'll either use it as an agent that we know a person has had a penicillin before and didn't respond.

02:23 Now, we only use this particular type of cephalosporin and serious infections.

02:28 I like to say that these are intensive care unit drugs, but not really.

02:32 I would say that they're ward at drugs.

02:35 So we tend to use them on the medical floor when people have really bad infections.

02:40 Let's move on to the fourth generation cephalosporins.

02:44 This category involves a very complicated drugs Cefepime is a perfect example of that.

02:51 Now, these drugs are zwitterions.

02:54 What's a zwitterion? A zwitterion is an ion or a drug that has two different charges on the same molecule.

03:02 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.

03:11 Okay, let's move on.

03:13 So a fourth generation cephalosporin like cefapime is more resistant to beta lactamase producing organisms.

03:21 Enterobacter is a particularly difficult infection to treat.

03:26 We often see this in very sick patients who are in the intensive care unit or on the ward.

03:34 So, let's say a person comes in.

03:36 You suspect that they have a beta-lactamase based infection.

03:39 Cefepime is a really good choice in this particular type of patient.

03:44 Now we move on to fifth generation cephalosporins.

03:48 It includes drugs like ceftaroline.

03:50 Now, I want to make a mention that not everyone accepts the whole nomenclature behind fifth generation cephalosporins.

03:57 There are some people who just say that all fifth generations are unclassified.

04:02 I'll leave that debate alone for a moment.

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

04:08 So you can see, that these fifth generation cephalosporins are larger, more complicated molecules.

04:15 Ceftaroline, has excellent MRSA coverage, and we will often use it in patients who are sick with MRSA.

04:23 This is another agent.

04:24 You can see it's a slightly simpler structure.

04:27 It has powerful antipseudomonas activity, and it also can work against VRE, which stands for Vancomycin-resistant Enterococcus.

04:37 Ceftolozane is another fifth generation cephalosporin.

04:41 We will often use this in intraabdominal infections that are complicated.

04:45 So intra abdominal infections tend to have a lot of gram-negative organisms.

04:50 They sometimes have gram-positive organisms.

04:53 And more importantly, they have anaerobic organisms.

04:58 And treating anaerobic organisms is notoriously difficult.

05:01 We have to resort to very complicated drugs.

05:04 This is an excellent choice for an abdominal infection.

05:08 Sometimes complicated urinary tract infections can be treated with this drug as well.

05:13 And when you think about it, urinary tract infections also tend to have a lot of gram-negative.

05:19 Sometimes they'll have anaerobic.

05:20 and sometimes they'll have Pseudomonas infections.

05:23 We will often combine it with tazobactam.

05:26 And remember that tazobactam is combined with other agents to like Piperacillin.

05:31 Finally we have the unclassified.

05:33 Now, maybe someday we'll call this the sixth generation. I don't know.

05:37 There's a whole host of them.

05:39 They haven't really been studied very much.

05:41 They're brand new.

05:43 And information will come out as they start to get more and more clinical usage.