Erdman - Macrolides Flashcards
Macrolide mechanism of action
Reversibly bind to the 50S ribosomal subunit (P site) inducing dissociation of peptidyl transfer RNA from the ribosome during the elongation phase
At what rate do macrolides kill bacteria
Macrolides are typically bacteriostatic unless at high concentrations against very susceptible targets
Mechanisms of resistance against macrolides
-Active efflux (low level resistance)
-Altered binding sites (high level resistance)
Does cross-resistance occur between macrolides?
Yes and also between clindamycin and Synercid in the case of altered binding sites
What are the macrolides?
-Erythromycin
-Clarithromycin
-Azithromycin
Which macrolides display the best activity against gram-positive aerobes?
-Erythro
-Clarithro (better than erythro)
What gram-positives do macrolides have activity against?
-PSSP (resistance is developing)
-MSSA (only if the patient is allergic to penicillins)
Which macrolides display the best activity against gram-negative aerobes?
-Azithro (better)
-Clarithro
What gram-negatives do macrolides have activity against?
-H. influenzae
-M. cararrhalis
-Neisseria spp.
What anaerobes do macrolides have activity against?
Upper airway anaerobes (no BDA)
Whatatypicals do macrolides have activity against?
-Legionella pneumophilia (DOC)
-Chlamydophila and chlamydia spp.
-Mycoplasma pneumoniae
-Ureaplasma urealyticum
Why is erythromycin not used much anymore?
It is not acid stable and causes GI discomfort
Why are macrolides not typically used for blood infections?
They have very large Vds and therefore have a low serum concentration
Can macrolides penetrate the CNS
Minimal CSF penetration
Which macrolide requires dose adjustment in renal insufficiency?
Clarithromycin is metabolized and partially eliminated by the kidney and needs dose adjustment when CrCl is below 30
Which macrolide has no interactions with CYP450 enzymes?
Azithromycin is excreted by biliary excretion
Half-life for azithromycin
68 hours
Are the macrolides removed during hemodialysis?
None of them are
Clinical uses of macrolides
-Community acquired pneumonia (used with ceftriaxone if the patient is hospitalized)
-STDs: single 1 gram dose of azithromycin
-Alternative for pen-allergic patients for group A strep URIs, bacterial endocarditis prophylaxis, syphilis and GC, and rheumatic fever prophylaxis
Macrolide adverse effects
-GI effects (not as common with newer agents but still seen)
-Thrombophlebitis
-QTc prolongation
How can you prevent GI effects with clarithro and azithro?
Take with food if possible
How can you prevent thrombophlebitis?
-Dilute dose
-Administer slowly
-Use a large vein
Which macrolides are inhibitors of the cytochrome P450 system in the liver?
Erythromycin and clarithromycin
Which drugs can be effected by the inhibition of the cytochrome P40 system in the liver?
-Theophylline
-Carbamazepine
-Cyclosporine
-Phenytoin
-Warfarin
-Digoxin
-Valproic acid
What is the one possible interaction with azithromycin?
Warfarin but this is still debatable
