Macrolides (FETT)

Antibacterials

CLARITHROMYCIN

ERYTHROMYCIN

bind to 23S ribosomal RNA molecule of the 50S subunit → blockage of translocation → inhibition of bacterial protein synthesis (bacteriostatic effect)

• CNS penetration: poor

• Route of elimination: biliary

• Atypical pneumonia caused by:

  • Mycoplasma pneumonia

  • Legionella pneumophila

  • Chlamydophila pneumoniae

• Bordetella pertussis

• STIs caused by Chlamydia

• Gram-positive cocci especially for the treatment of streptococcal infection in patients who are allergic to penicillin)

• Neisseria spp.

  • Second-line prophylaxis for N. meningitidis

  • Dual therapy with ceftriaxone for N. gonorrhoeae (azithromycin)

• Mycobacterium avium

  • Prophylaxis: azithromycin

  • Treatment: azithromycin, clarithromycin

• H. pylori (clarithromycin is the part of triple therapy )

• Ureaplasma urealyticum

• Babesia spp. (azithromycin in combination with atovaquone)

• Increased intestinal motility → GI upset

• QT-interval prolongation , arrhythmia

• Acute cholestatic hepatitis

• Eosinophilia

• Rash

• Increased risk of hypertrophic pyloric stenosis (erythromycin and azithromycin) in infants up to 6 weeks of age

• Erythromycin enhances the effect of oral anticoagulants (e.g., warfarin).

• Erythromycin and clarithromycin

  • Increased theophylline serum concentrations

  • CYP3A4 inhibition (cytochrome P450 inhibitors)

• All macrolides (except azithromycin) have a short half-life.

• Erythromycin is used off-label for the treatment of gastroparesis because it increases GI motility.

• Erythromycin estolate and clarithromycin are contraindicated in pregnant women (potentially hazardous to the fetus)

  • Erythromycin estolate use in pregnant women during the first trimester is associated with an increased risk of hepatic failure in the women.

  • All the other forms of erythromycin (e.g., ethylsuccinate, stearate, etc.) can be safely used.

• Azithromycin and clarithromycin are contraindicated in patients with hepatic failure (erythromycin should be used cautiously).

• Consider use of erythromycin in children < 12 years of age only if benefits outweigh the risks, as safety in this population has not been established.

• Consider use of clarithromycin and azithromycin in children < 6 months of age only if benefits outweigh the risks, as safety in this population has not been established.

• Cautious use in breastfeeding women

• Cautious use of clarithromycin in patients with renal failure

Methylation of the binding site of 23S rRNA prevents the macrolide from binding to rRNA.