Skin and soft tissue infection

Question 1

Macrolides

Common indications

Answer 1

1. Respiratory, skin and soft tissue infections as an alternative to penicillin when this is contraindicated
2. Severe pneumonia including organisms such as legionella pneumophila and Mycoplasma pneumoniae
3. Eradication of H.pylori in combination with PPI and either amoxicillin or metronidazole

Question 2

Macrolides

MOA

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.
• It has a relatively broad spectrum of activity against Gram-positive and some Gram-negative organisms.
• Synthetic macrolides (e.g. clarithromycin and azithromycin) have increased activity against Gram-negative bacteria, particularly Haemophilus influenzae.
• Bacterial resistance to macrolides is common, mainly due to ribosomal mutations preventing macrolide binding.

Question 3

Macrolides

Adverse effects

Answer 3

• 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 4

Macrolides

Warnings

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

Macrolides

Interactions

Answer 5

• 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 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 6

Other agents

Answer 6

• Penicillins
• Antipseudomonal penicillins
• Penicillinase-resistant penicillins