Macrolides - Erythromycin

Question 1

What are macrolides (like erthyromycin, clarithromycin) used for?

Answer 1

1) respiratory and skin/ soft tissue infections as an alternative to a penicillin (e.g. in penicillin allergy)
2) Severe pneumonia (macrolides+ penicillin help to cover atypical organisms e.g. legionella pneumophila + mycoplasma pneumoniae)
3) eraication of h.pylori as part of triple therapy (PPI + macrolide + amoxicillin/metronidazole)

Question 2

Why do we use a combination of penicillin and erythromycin to treat severe pneumonia?

Answer 2

erythromycin + penicillin for severe pneumonia to help cover atypical organisms e.g. Legionella Pneumophila and Mycoplasma Peumoniae

Question 3

What is erythromycin (macrolide) used in conjuction with in the triple eradication therapy of H.Pylori?

Answer 3

1) PPI + erythromycin + amoxicillin

2) PPI + erythromycin + metronidazole

Question 4

How do macrolides (e.g. erythromycin / clarithromycin) work?

Answer 4

They are bacteriotstatic.
They stop bacterial growth by inhibiting bacterial protein synthesis - they bind to the 50S subunit and block translocation.

Question 5

What bacteria is erythromycin affective against?

Answer 5

Gram positive bacteria and some gram negatives.

Question 6

What bacteria does synthetic macrolides like clarithromycin and azithromycin have activity against?

Answer 6

• gram postive

- increased gram negative particularly haemophilus influenzae

Question 7

Why is macrolide resistance common?

Answer 7

ribosome mutations preventing binding

Question 8

What are the side effects of macrolides (e.g. erythromycin / clarithromycin)

Answer 8

1) GI upset (taken orally)
- nausea, vomiting, abdo pain, diarrhoea

2) thrombophlebitis (IV)
3) Allergy
4) antibiotic associated colitis
5) Cholestatic jaundice
6) prolonged QT interval —-> arrhythmias
7) ototoxicity (at high dose)

Question 9

what are the contraindications of macrolides?

Answer 9

• don’t give in history of macrolide sensitivity,
• sever hepatic impairment
• sever renal impairment

Question 10

How are macrolides eliminated?

Answer 10

Mainly via liver, small renal contribution

Question 11

Why should clarithromycin and erythromycin be avoided with warfarin and statins?

Answer 11

Clarithromycin and erythromycin inhibit cytochrome P450 enzymes so increase the plasma concentrations of drugs metabolised by P450 enzymes.

e. g.
- warfarin (bleeding risk)
- statins (myopathy risk)

Question 12

Macrolides such as erythromycin should be avoided with other QT prolonging drugs due to the risk of arrhythmias. Give examples of these drugs

Answer 12

• amiodarone
• antipsychotics
• quinine
• quinolone antibiotics
• SSRIs

Question 13

What is the usual dosage of clarithromycin?

Answer 13

250-500 mg twice daily for 7 days

Question 14

Why should IV clarithromycin not be given as an IV bolus or IM?

Answer 14

Macrolides should be infused over 60mins to reduce risk of arrhythmias