Macrolides Flashcards
What are the macrolides in clinical use today?
Erthromycin
Clarithromycin
Azithromycin
Clarithromycin and azithromycin are preferentially used in clinical practice. Why?
Better spectrum of activity
More tissue penetration
Improved PK properties
Improved tolerability
Macrolides
Mechanism of Action
Cidal or Static?
Bind and inhibit the bacterial 50S ribosomal subunit
Bacteriostatic, but may be cidal at high concs
Time or concentration dependent activity for the three macrolides?
Erthryomycin and Clarithromycin have TIME dependent activity
Azithromycin is CONCENTRATION dependent activity
Mechanisms of Resistance to Macrolides
- Altered target sites (erm gene)
- Efflux pumps (mef gene)
Macrolides
Spectrum of Activity
Gram Positive Aerobes
Clarithro > Erythro > Azithro
MSSA PSSP Group and viridians strep Bacillus Corynebacterium
Macrolides
Spectrum of Activity
Gram Negative Aerobes
Azithro > Clarithro > Erythro
H. influenzae
M. catarrhalis
Neisseria spp.
NO activity against Enterobacteriaceae
Macrolides
Spectrum of Activity
Atypical Bacteria and other bacteria
Legionella pneumophila
MAC (Mycobacterium avium complex)
Macrolides
Absorption
Erythromycin has variable absorption, but clarithro and azithro have better oral absorption.
Macrolides
Distribution
CSF?
Clarithro and azithro have better tissue concs.
Minimal CSF penetration
Macrolides
Elimination
Erythromycin is excreted in bile and metabolized by CYP450.
Clarithromycin is metabolized and partially eliminated by kidney.
Macrolides
Clinical Uses
Pharyngitis Tonsillitis Sinusitis CA- Pneumonia Uncomplicated Skin infections STDs MAC
Used for penicillin allergic patients
Macrolides
Adverse Effects
GI- nausea, vomiting
Thrombophlebitis (inflammation of a wall of a vein with thrombosis)
Prolonged QT interval
Reversible tinnitus or deafness
Macrolides
Potentially fatal drug rxm
Colchicine (for gout)
Which macrolides inhibit CYP450 enzymes? Why is this important?
Erythromycin and clarithromycin ONLY.
May increase serum concentrations of other drugs, which can cause toxicity.
