Erythromycin

Erythromycin is the original macrolide, used for atypical respiratory infection, pertussis, chlamydia in pregnancy, Campylobacter infection and as a prokinetic. It has many drug interactions and prolongs the QT interval.

Classification. Macrolide.

Mechanism. Binds the 50S ribosomal subunit and blocks protein synthesis; bacteriostatic, bactericidal at high dose against some organisms. Also agonises motilin receptors.

Spectrum. Streptococci, pneumococci (resistance common), MSSA, Corynebacterium diphtheriae, Bordetella pertussis, Campylobacter, Legionella, Mycoplasma pneumoniae, Chlamydia and Ureaplasma. Not active against Enterobacterales or Pseudomonas; Haemophilus is poorly covered.

Pharmacokinetics. Oral bioavailability varies by salt (stearate and ethylsuccinate better with food; base needs enteric coating). Half-life 1.5 to 2 hours. Hepatic metabolism by CYP3A4; potent inhibitor of CYP3A4 and P-glycoprotein. Biliary excretion.

No loading dose. Maximum 4 g daily in adults.

Adults, oral. 250 to 500 mg every 6 hours or 500 mg to 1 g every 12 hours (ethylsuccinate 400 to 800 mg every 6 to 12 hours).

• Pertussis: 500 mg every 6 hours for 14 days.
• Atypical pneumonia, Legionella (alternative): 500 mg every 6 hours for 7 to 14 days.
• Campylobacter enteritis (severe): 500 mg every 12 hours for 5 days.
• Chlamydial infection in pregnancy (alternative): 500 mg every 6 hours for 7 days (or 250 mg every 6 hours for 14 days if poorly tolerated).
• Preterm prelabour rupture of membranes: 250 mg every 6 hours for 10 days.
• Rheumatic fever secondary prevention in penicillin allergy: 250 mg every 12 hours.
• Prokinetic (gastroparesis, upper gastrointestinal bleeding before endoscopy): 250 mg oral every 8 hours; 250 mg IV over 30 minutes, 30 to 120 minutes before endoscopy.

Adults, IV (lactobionate). 500 mg to 1 g every 6 hours as an infusion at 5 mg/mL over 60 minutes; maximum 4 g daily.

Children. 30 to 50 mg/kg/day divided every 6 hours (maximum 2 g daily in mild infection); up to 100 mg/kg/day (maximum 4 g) in severe infection. Neonates: 10 mg/kg every 6 to 8 hours; avoid in the first 2 weeks unless needed because of pyloric stenosis risk.

Alternatives. Azithromycin, clarithromycin, doxycycline, amoxicillin.

Contraindications. Hypersensitivity to macrolides; history of QT prolongation or torsades; co-administration with ergot alkaloids, simvastatin, lovastatin, colchicine in renal or liver impairment, or other contraindicated CYP3A4 substrates.

Adverse effects. Nausea, vomiting, abdominal cramps, diarrhoea (motilin effect). Serious: QT prolongation and torsades, cholestatic hepatitis (mainly with the estolate salt), ototoxicity (high-dose IV, renal failure), infantile hypertrophic pyloric stenosis, exacerbation of myasthenia gravis, Clostridioides difficile infection, phlebitis.

Interactions. - Simvastatin and lovastatin (rhabdomyolysis), atorvastatin (reduce dose), colchicine (toxicity), ergot alkaloids (ergotism), carbamazepine (toxicity), ciclosporin and tacrolimus (toxicity). - Warfarin (INR rise), theophylline (toxicity), digoxin (toxicity), midazolam, sildenafil, clopidogrel (reduced effect). - QT-prolonging drugs (amiodarone, haloperidol, ondansetron, fluoroquinolones).

Common prescribing errors. Missing CYP3A4 interactions, giving the IV form as a rapid push, prescribing the estolate salt in pregnancy, and using it when azithromycin is better tolerated.

Special groups. - Pregnancy: acceptable (avoid the estolate salt). Breastfeeding: compatible but monitor infants under 6 weeks. - Older adults: increased QT and interaction risk. - Kidney impairment: creatinine clearance under 10 mL/min limit to 2 g daily. - Liver impairment: caution; avoid the estolate salt. - Region: used where azithromycin is not available or is too costly.

Preparation. IV: reconstitute with sterile water for injection (not saline), then dilute to 1 to 5 mg/mL in 0.9% sodium chloride and infuse over 60 minutes. Take oral base or enteric tablets on an empty stomach and ethylsuccinate with food.

Baseline and monitoring. - Baseline: medication review for interactions, ECG when other QT drugs are used, liver tests. - During treatment: ECG in high-risk patients on IV therapy; liver tests if prolonged; potassium and magnesium kept normal.

Stop rules. Stop for syncope, palpitations, QTc over 500 ms, jaundice or severe diarrhoea.

Referral and escalation. Seek cardiology advice for torsades and infectious diseases for resistant atypical infection.