Infectious diseases: Pharmacology - Macrolides

Question 1

Four examples of macrolides

Answer 1

Erythromycin
Azithromycin
Clarithromycin
Roxithromycin

Question 2

Mechanism of action of macrolides

Answer 2

Binds reversibly to 50S ribosomal subunit to inhibit bacterial protein synthesis

Question 3

Macrolides: bacteriostatic or bactericidal?

Answer 3

Both: bactericidal at high concentrations

Question 4

Major indications for use of macrolides

Answer 4

Corynebacterial infections (diphtheria, erythrasma, sepsis)
Chlamydial infections (respiratory, neonatal, ocular, genital)
CAP (covers pneumococci, mycoplasma, legionella)
Penicillin substitute in setting of penicillin allergy

Question 5

Coverage of macrolides

Answer 5

Broad-spectrum
Gram positives: especially pneumococcus, streptococcus, staphylococcus, corynebacterium
Gram negatives: neisseria, B. pertussis, bartonella (cat scratch disease), some rickettsiae, treponema pallidum, campylobacter
Also mycoplasma, legionella, chlamydia, helicobacter, listeria, certain mycobacteria

Question 6

Mechanisms of resistance in macrolides. Which are the most common in Gram positives?

Answer 6

1. Decreased permeability of cell membrane or active efflux*
2. Production of esterases that hydrolyse macrolides
3. Ribosome protection by modification of ribosomal binding site (either by chromosomal mutation or methylase*)

• most common mechanisms of resistance are active efflux and methylase production by Gram positives

Question 7

Describe the pharmacokinetics of macrolides

Answer 7

Absorption: destroyed by stomach acid (needs enteric coating; except clarithromycin which is acid-stable), food improves absorption
Distribution: widely distributed except brain and CSF, crosses placenta
Metabolism: not metabolised
Excretion: majority bile and faeces (only 5% urine)

Question 8

Four adverse reactions attributable to macrolides

Answer 8

1. GIT upset (nausea, vomiting, diarrhoea)
2. Acute cholestatic hepatitis
3. Allergy: fever, eosinophilia, rash
4. Cytochrome P450 inhibitor (except azithromycin)

Question 9

Which macrolide antibiotic is not a cytochrome P450 inhibitor?

Answer 9

Azithromycin