Macrolides And Ketolide

Question 1

Are Macrolides/Ketolides bacteriostatic or -icidal?

Answer 1

Bacteriostatic. Rely on adequate T/B cells and complement defense
-suppress cellular activity
Except they are bactericidal to strep pneumonia and strep pyrogenes

Question 2

Are Macrolides/ketolides concentration dependent or time dependent?

Answer 2

Concentration dependent

Question 3

What is the bacteriostatic nemonic?

Answer 3

We’re ECSTaTIC about bacteriostatics!
Erythromycin, Clinda, Sulfa, Trimethorprim, Tetracyclines, chloramphenicol

Question 4

What is the bactericidal nemonic?

Answer 4

Very Finely Proficient At Cell Murder
-Vanc, Fluoroquinolones, PCNs, Aminoglycosides, Cephalosporins, Metronidazole

Question 5

What class of drug to erythromycin, clarithromyacin, and azithromyacin fall under?

Answer 5

Macrolides; Protein Synthesis Inhibitors

Question 6

What is the MOA of Macrolides?

Answer 6

Inhibit protein synth by binding to domain II and V on 50s ribosomal subunits; makes the bacteria not work as well

Question 7

Macrolides share domain binding sites with what other abx, and, therefore, should not be used together?

Answer 7

Clindamycin, lincomycin, chloramphenicol, streptogramins

Question 8

Macrolides offer good coverage for what atypical bacteria?

Answer 8

Mycoplasma pneumonia and legionella
-mycoplasmas like to hide in cells and Macrolides offer good cell penetration.
-mycoplasmas don’t have cell walls, so cell wall synthesis inhibitors can’t work on them

Question 9

What Gram + bugs to Macrolides cover?

Answer 9

Group A strep, strep pneumonia, strep pyogenes, strep viridans, staph aureus MSSA (NOT MRSA*), listeria

Question 10

What Gram - coverage to Macrolides offer?

Answer 10

Bordatella purtussis, campylobacter, clamydia, H. influenzae, H. Pylori, legionella, MAC (except eryth), gonorrhea, shigella, S. Typhi

Question 11

What three drugs are used to treat H. Pylori

Answer 11

Clarithromyacin, amoxicillin, and a PPI

Question 12

What are the general uses for Macrolides?

Answer 12

• upper and lower resp infections (otitis media, pharyngitis (s. Pyogenes), sinusitis, CAP)
• Cervicitis, chlamydia, bacterial COPD exacerbations, whooping cough (pertussis)
• bacterial conjunctivitis, corneal ulceration, prophylaxis of ophthalmia neonatorum

Question 13

What is the mechanism of resistance against Macrolides?

Answer 13

• Methylation of guanine reside on the rRNA, making them less effective at protein synth, but also making Macrolides less effective or
• mutation of domain V, causing reduced binding to eryth and clarith or
• efflux pumps kicking the abx out

Question 14

Which Macrolide has the most convenient dosing schedule?

Answer 14

Azithromyacin; Zpack is 500mg per day, 250mg 2-5d.
- longest half life of Macrolides: 68h

Question 15

Which macrolide has the least convenient dosing schedule?

Answer 15

Erythromycin. 250-500mg q6h

Question 16

What are the SE for azithromyacin?\

Answer 16

• GI upset
• QT prolong
• bad taste, hearing loss
• antacids decrease levels

Question 17

What are the SE of clarithromyacin?

Answer 17

Bad taste, GI upset, QT prolong; adjust for renal fx, hearing loss, hold statins dt tendon rupture risk

Question 18

What are the SE of erythromycin?

Answer 18

Diarrhea (the worst), QT prolong, SJS, hearing loss
- contra w myasthenia gravis, liver disease, pimozide, and alkaloids can cause ergot tox

Question 19

What is azithromyacin’s relationship with CYP3A4?

Answer 19

No interaction

Question 20

What is clarithromyacin’s relationship with CYP3A4?

Answer 20

Moderate inhibito

Question 21

What is erythromyacin’s relationship with CYP3A4?

Answer 21

MAJOR inhibitor

Question 22

Fidaxomicin is used for?

Answer 22

C. Diff

Question 23

Which Macrolides do you use opthalmically?

Answer 23

Erythromycin and azithromyacin (use DuraSite as it’s an aqueous solution)

Question 24

What is the main difference between Macrolides and ketolide?

Answer 24

Ketolide lacks the 3-L-cladinose side group, binds to domains II and V on the 23s rRNA of the 50s subunit
- this different retains its activity against methylation of domain V that causes resistance to other Macrolides
- allows it to work against MDR S. Pneumoniae, CAP, and bacterial infections of chronic bronchitis

Question 25

Ketolides work against which gram + bugs?

Answer 25

Group A strep, strep pneumonia, ***MDRSP, strep pyogenes, strep viridans, staph aureus (MSSA)

Question 26

Ketolides work against which Gram - bugs?

Answer 26

H. Influenzae, m. Catarrhalis
- also good atypical coverage

Question 27

Which drug is a Ketolides and what are its SEs?

Answer 27

Telithromycin
- visual disturbances, liver tox, QT prolong

Question 28

Telithromycin is contraindicated in which cases?

Answer 28

• Dt being a CYP3A4 inhibitor stop: lovastatin, simvastatin, atorvastatin; caution with dig and metoprolol
• contra with myasthenia gravis
• renal adjustment