Macrolides and Ketolides – Bacterial Protein Synthesis Inhibitors (Antibiotics)

00:00 Let's move on to the macrolides antibiotics.

00:03 These macrolides antibiotics are very important group of medications because we use them all the time.

00:08 Specially in respiratory infections.

00:11 Now these agents are blocking the 50 S unit from transcription.

00:15 Important agents include erythromycin and clarithromycin.

00:19 They're rapidly eliminated from the body.

00:22 They're considered broad spectrum antibiotics.

00:25 And as I said before they're most commonly used in respiratory infections.

00:29 Azithromycin concentrates into macrophages and other tissues and it is actually eliminated quite slowly.

00:37 This particular medicine also effective in gonarrhea.

00:41 The nice thing about azithromycin is that you can actually give it as a three day set of medications but it will last for ten days.

00:48 So the killing activity actually lasts much longer than the drug is actually in the body.

00:55 Other medications are more narrow spectrum within this drug group.

00:59 The selectivity targets are generally gram positive anaerobes and aerobes.

01:04 And these are used often in clostridium difficile infections.

01:10 Let's talk about the resistance to macrolides antibiotics.

01:14 It's actually quite an interesting topic because of the mechanism and the resistance patterns.

01:20 Now you actually will develop ejector pump mechanisms in some bacteria that literally pump out the drug, the active drug out of the cell.

01:28 It's quite an interesting phenomenon.

01:30 The other thing that may happen in resistance patterns is changing the binding site of the macrolide by perhaps adding a methyl group.

01:38 Now the problem here is that there is a 100% cross resistance pattern between one macrolide and another.

01:45 So if for example you give a patient clarithromycin for a respiratory infection on week 1, they come back with resistance and you decide to try a different medication, there's going to be cross resistance between those two, say between clarithromycin and azithromycin.

02:01 There's partial cross resistance with drugs like clindamycin and the streptogramins as well.

02:08 And the resistance in the enterobactriaceae species and that is due to the production of drug destroying esterases.

02:16 Not because of the ejector pump.

02:19 So it's a slightly different mechanism but still 100% cross resistant pattern.

02:29 Let's move on to the ketolides.

02:31 Now the ketolides are structurally similar to the macrolides.

02:35 And I haven't put a separate triangle here.

02:37 Let's just say that that triangle is both for K and M.

02:40 It has the same mechanism of action and the same antibiotic spectrum as the macrolides as well.

02:46 Now a lot of times macrolides resistance strains are susceptible to the ketolides.

02:51 And there is an increase affinity to the ribosomes with the ketolides than with the macrolides.

02:56 They are also poorly ejected through ejector pores which is why we think these maybe really good choice for some people.

03:05 So they sound very similar to the macrolides.

03:08 They're used in community acquired pneumonia.

03:11 They're nice because they are given once a day and they are oral medications.

03:15 Downside.

03:16 They can act through cyctochrome 3A4 and they do prolong the QT interval on the ECG which potentially could mean that they could be proarrhythmic.