Prescribing Notes: Macrolide Antibiotics

Macrolide antibiotics are widely used in clinical practice to treat a range of bacterial infections, particularly respiratory, skin, and soft tissue infections. Their broad-spectrum activity and tolerability make them essential in outpatient and inpatient settings. However, prescribing macrolides requires careful consideration of their indications, side effects, contraindications, and appropriate patient counselling to ensure safe and effective use.

1. Indications for Macrolide Antibiotics

Macrolides are effective against Gram-positive bacteria, atypical organisms, and some Gram-negative pathogens. Common indications include:

• Respiratory Infections:
  • Community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae, Legionella spp., and Chlamydophila pneumoniae.
  • Exacerbations of chronic bronchitis or COPD.
  • Pertussis (whooping cough) caused by Bordetella pertussis.
• Ear, Nose, and Throat Infections:
  • Otitis media and sinusitis (second-line therapy).
  • Pharyngitis (for patients allergic to penicillin).
• Skin and Soft Tissue Infections:
  • Cellulitis caused by Streptococcus or Staphylococcus species.
• Gastrointestinal Infections:
  • Helicobacter pylori eradication (combined therapy with other antibiotics and PPIs).
  • Campylobacter gastroenteritis.
• Sexually Transmitted Infections:
  • Chlamydial infections (azithromycin).
  • Gonorrhea adjunct treatment.
• Other Indications:
  • Prophylaxis for Mycobacterium avium complex in HIV patients.
  • Diphtheria and Legionnaires’ disease.

2. Common Macrolide Antibiotics

• Erythromycin: Older macrolide; widely used but has significant gastrointestinal side effects.
• Clarithromycin: Better tolerability, extended activity, and more convenient dosing.
• Azithromycin: Preferred for respiratory infections and STIs due to once-daily dosing and long half-life.

3. Side Effects

Macrolides are generally well-tolerated, but common and serious side effects include:

Common Side Effects:

• Gastrointestinal:
  • Nausea, vomiting, abdominal pain, and diarrhea (especially erythromycin).
  • Metallic taste (more common with clarithromycin).
• Headache and Fatigue:
  • Mild headache and lethargy may occur.

Serious Side Effects:

• Cardiac:
  • QT interval prolongation, which may cause torsades de pointes arrhythmia.
  • Risk is higher in patients with electrolyte imbalances or taking other QT-prolonging drugs.
• Hepatic:
  • Cholestatic hepatitis, particularly with prolonged use.
• Hypersensitivity:
  • Rare but may include rash, itching, or anaphylaxis.
• Hearing Loss:
  • Reversible sensorineural hearing loss at high doses.

4. Contraindications

Macrolides are contraindicated in:

1. Patients with Known Allergy to macrolide antibiotics.
2. Severe Hepatic Impairment: Risk of liver toxicity.
3. Concurrent Use of QT-Prolonging Drugs:
   • Examples include amiodarone, sotalol, and certain antipsychotics.
4. Previous History of Cholestatic Jaundice due to macrolides.

5. Cautions and Warnings

Prescribe macrolides cautiously in the following situations:

• Cardiac Conditions:
  • Patients with existing arrhythmias, bradycardia, or a history of QT prolongation.
• Drug Interactions:
  • Macrolides inhibit CYP3A4, which can increase plasma concentrations of:
    • Statins (risk of rhabdomyolysis).
    • Warfarin (increased bleeding risk).
    • Digoxin (toxicity risk).
• Renal Impairment:
  • Adjust the dose for clarithromycin in renal failure (CrCl < 30 mL/min).
• Pregnancy and Lactation:
  • Clarithromycin is generally avoided in pregnancy unless absolutely necessary.
  • Azithromycin is considered safer for use during pregnancy.

6. Patient Counselling Points

When prescribing macrolides, ensure patients understand the following:

1. Medication Use:
   • Take the full course of antibiotics, even if symptoms improve before completion.
   • Azithromycin may be taken with or without food.
   • Clarithromycin and erythromycin are better tolerated when taken with food.
2. Possible Side Effects:
   • Inform patients of common gastrointestinal side effects like nausea or diarrhea.
   • Advise them to seek medical attention if they experience palpitations, dizziness, or severe abdominal pain.
3. Drug Interactions:
   • Avoid grapefruit juice (increases macrolide levels).
   • Inform your doctor about other medications you are taking (e.g., statins, anticoagulants).
4. Cardiac Symptoms:
   • Advise patients to report any signs of irregular heartbeat, chest pain, or shortness of breath.
5. Storage:
   • Store macrolide suspensions as instructed (some require refrigeration).
6. Pregnancy and Breastfeeding:
   • Inform the prescriber if pregnant or breastfeeding to ensure safe prescribing.

7. Summary Table

Parameter	Erythromycin	Clarithromycin	Azithromycin
Indications	Broad, respiratory, GI	Respiratory, H. pylori	Respiratory, STIs, GI
Dosing	Multiple times daily	Twice daily	Once daily
GI Side Effects	Most frequent	Moderate	Least frequent
QT Prolongation Risk	High	Moderate	Lower compared to others
CYP3A4 Interactions	Strong inhibitor	Moderate inhibitor	Minimal inhibition
Pregnancy Safety	Caution	Avoid	Relatively safe

8. Conclusion

Macrolide antibiotics are effective and versatile agents widely used in clinical practice. However, their potential for drug interactions, QT prolongation, and gastrointestinal side effects requires careful prescribing and close monitoring. By understanding indications, contraindications, and patient counselling points, healthcare professionals can ensure safe and effective use of macrolides, improving patient outcomes while minimizing risks.