Cephalosporins – Cell Wall Synthesis Inhibitors (Antibiotics)

00:01 Next we have is 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 negative organisms 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.

00:27 However, a cefazolin does not have much effectiveness against gram negative bacteria so for example if you had a urinary tract infection, cefazolin is not going to be a 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.

00:49 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 it as a second generation cephalosporins as being respiratory drugs.

01:09 Why is that? Because 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 Hemophilus influenzae so, if we have a person who has either strep infection or Hemophilus infection we don't know, we'll often use cefuroxime.

01:33 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.

01:46 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, 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 so sometimes we'll either use it as an agent that we know a person has had a penicillin before and didn't respond.

02:21 Now we only use this particular type of cephalosporin in serious infections.

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

02:32 I would say that they are ward drugs so we tend to use them on the medical floor when people have really bad infections.

02:38 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.

02:49 Now, these drugs area zwitterions. 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.

03:06 As zwitterion has a positive charge on one end and a negative charge on another.

03:10 Okay, let's move on.

03:11 So a fourth generation cephalosporin like cefepime is more resistant to beta lactamase producing organisms.

03:20 Enterobacter is a particular 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.

03:31 This drug is often used in infections that are caused by MR resistant staphylococci.

03:39 So, let's say a person comes in, they have a methicillin-resistant staphylococci, you suspect that they have a beta lactamase base infection, cefepime is a really good choice in this particular type of patient.

03:52 Now, we move on to the fifth generation cephalosporins.

03:56 It includes drugs like ceftaroline.

03:59 Now, I wanna make a mention that not everyone accepts the whole nomenclature behind fifth generation cephalosporins, 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 so you can see that these fifth generations cephalosporins are larger, more complicated molecules. Ceftaroline has excellent MRSA coverage and we will often use it in patients who are sick with MRSA. This is another agent.

04:33 You can see it's a slightly simpler structure, it has powerful antipseudomonal activity and it also can work versus VRE which stands for vancomysin resistant enterococchi.

04:45 Ceftolozane is another fifth-generation cephalosporin.

04:49 We will often use this in intra-abdominal infections that are complicated so intra-abdominal infections tend to have a lot of gram-negative organisms, they sometimes have gram positives organisms and more importantly, they have anaerobic organisms, and treating anaerobic organisms is notoriously difficult.

05:10 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 and when you think about it urinary tract infections also tend to have a lot of gram negative, sometimes they'll have anaerobic and sometimes they'll have pseudomonas infections.

05:31 We will often combine it with tazobactam and remember that tazobactam is combined with other agents too like piperacillin.

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

05:50 They're brand new and information will come out as they start to get more and more clinical usage.