Macrolides

Question 1

Example of a Macrolide

Answer 1

Erythromycin

Question 2

How do Macrolides work?

Answer 2

. Macrolides inhibit bacterial protein synthesis. They bind to the 50S subunit of the bacterial ribosome and block translocation, a process required for elongation of the polypeptide chain. Inhibition of protein synthesis is ‘bacteriostatic’ (stops bacteria growth), which assists the immune system in killing and removing bacteria from the body.

Question 3

Indications for macrolides

Answer 3

Treatment of respiratory and skin and soft tissue infections as an alternative to a penicillin when this is contraindicated by allergy.

In severe pneumonia added to a penicillin to cover atypical organisms including Legionella pneumophila and Mycoplasma pneumoniae.

Eradication of Helicobacter pylori (for example causing peptic ulcer disease) in combination with a proton pump inhibitor and either amoxicillin or metronidazole.

Question 4

Contraindications for macrolides?

Answer 4

Macrolides should not be prescribed if there is a history of macrolide hypersensitivity, although they are a useful option where penicillin is contraindicated by allergy as there is no cross-sensitivity between these drug classes.

Macrolide elimination from the body is mostly hepatic with a small renal contribution, such that caution is required in severe hepatic impairment and dose reduction in severe renal impairment.

Question 5

Side effects of macrolides

Answer 5

Adverse effects are most common and severe with erythromycin, but can occur with any macrolide.

Macrolides are irritant, causing nausea, vomiting, abdominal pain and diarrhoea when taken orally and thrombophlebitis when given IV.

Other important side effects include allergy, antibiotic-associated colitis (see Penicillins, broad-spectrum), liver abnormalities including cholestatic jaundice, prolongation of the QT interval (predisposing to arrhythmias) and ototoxicity at high doses.

Question 6

Interactions of macrolides

Answer 6

Erythromycin and clarithromycin (but not azithromycin) inhibit cytochrome P450 enzymes. This increases plasma concentrations and risk of adverse effects with drugs metabolised by P450 enzymes. For example, with warfarin there is an increased the risk of bleeding and with statins an increased risk of myopathy.

Macrolides should be prescribed with caution in patients taking other drugs that prolong the QT interval or cause arrhythmias, such as amiodarone, antipsychotics, quinine, quinolone antibiotics and SSRIs.

Question 7

Elimination of Macrolides

Answer 7

Mostly hepatic with a small renal contribution

Question 8

Patient information on macrolides

Answer 8

Explain that the aim of treatment is to get rid of infection and improve symptoms. For oral treatment, encourage the patient to complete the prescribed course. Before prescribing, always check with your patient personally or get collateral history to ensure that they are not allergic to macrolides. Warn them to seek medical advice if a rash or other unexpected symptoms develop. If an allergy develops during treatment, give the patient written and verbal advice not to take this antibiotic in the future and make sure that the allergy is clearly documented in their medical records.

Clinical tips
In patients with lower respiratory tract infections (LRTI), macrolides should generally only be added to penicillin treatment if there is evidence of pneumonia (e.g. consolidation on the chest X-ray). Macrolides are required to cover penicillin-resistant atypical organisms, e.g. Legionella pneumophila and Mycoplasma pneumoniae, that cause pneumonia but do not cause other LRTI, e.g. COPD exacerbations.

Clarithromycin is the most commonly prescribed macrolide in the UK, being more stable and causing fewer adverse effects than erythromycin, and being cheaper than azithromycin