Erythromycin: A Complete Clinical Reference

What Is Erythromycin?

Erythromycin is a macrolide antibiotic first isolated in 1952 from the soil bacterium Saccharopolyspora erythraea (originally classified as Streptomyces erythreus) by Filipino scientist Abelardo Aguilar. It was introduced into clinical practice by Eli Lilly later that year and has remained in continuous medical use for over seven decades.

As one of the oldest macrolides, erythromycin serves as the structural parent compound for newer derivatives such as azithromycin and clarithromycin. It is included on the World Health Organization's List of Essential Medicines, reflecting its global importance — particularly in settings where penicillin allergy limits treatment options.

Erythromycin is available in multiple formulations: oral tablets and capsules (including enteric-coated and delayed-release forms), oral suspensions, intravenous preparations, topical gels and solutions for acne, and ophthalmic ointment for neonatal conjunctivitis prophylaxis. This versatility across routes of administration accounts for its enduring clinical relevance. Detailed information on each dosage form is available on the usage and dosage page.

Mechanism of Action

Erythromycin exerts its antibacterial effect by binding reversibly to the 23S ribosomal RNA component of the 50S ribosomal subunit in susceptible organisms. This binding blocks the translocation step of protein synthesis, preventing the growing peptide chain from moving from the A-site to the P-site on the ribosome. The net result is inhibition of bacterial protein synthesis.

At therapeutic concentrations, erythromycin is primarily bacteriostatic — it inhibits bacterial growth rather than killing organisms directly. However, it can be bactericidal at higher concentrations or against particularly susceptible species. Its spectrum of activity covers many gram-positive cocci (including Streptococcus pneumoniae, Streptococcus pyogenes, and methicillin-susceptible Staphylococcus aureus), some gram-negative organisms (such as Haemophilus influenzae, Neisseria, and Bordetella pertussis), and atypical pathogens including Mycoplasma pneumoniae, Chlamydia trachomatis, and Legionella pneumophila.

For a deeper exploration of the macrolide drug class, bacterial spectrum, and resistance mechanisms, see the basics section.

Clinical Indications

Erythromycin is approved for a range of bacterial infections. Its primary role today is as an alternative for patients with penicillin or beta-lactam allergies, though it retains first-line status in several specific contexts.

Respiratory Tract Infections

Erythromycin is effective against community-acquired pneumonia caused by typical and atypical pathogens, acute bacterial exacerbations of chronic bronchitis, and pharyngitis or tonsillitis caused by group A streptococci in penicillin-allergic patients. It is also a primary agent for treating Legionella pneumophila pneumonia and for prophylaxis and treatment of pertussis (whooping cough).

Skin and Soft Tissue

Oral and topical formulations are used for mild-to-moderate skin infections, including impetigo, erysipelas, and erythrasma. Topical erythromycin (2% gel or solution) remains a widely prescribed treatment for inflammatory acne vulgaris, often in combination with benzoyl peroxide to mitigate resistance.

Sexually Transmitted Infections

Erythromycin is an established alternative for uncomplicated chlamydial infections, particularly in pregnant patients for whom doxycycline and fluoroquinolones are contraindicated. It is also used in the treatment of chancroid and granuloma inguinale.

Ophthalmic Use

Erythromycin 0.5% ophthalmic ointment is the standard prophylactic agent applied to newborns to prevent ophthalmia neonatorum caused by Neisseria gonorrhoeae and Chlamydia trachomatis.

Off-Label: Gastroparesis

Erythromycin acts as a motilin receptor agonist at sub-antimicrobial doses, stimulating gastric motility. It is used off-label (typically IV in acute settings) to treat gastroparesis, particularly diabetic gastroparesis, when other prokinetic agents are insufficient. However, tachyphylaxis (reduced effectiveness over time) limits long-term oral use for this indication.

Full dosage details, administration guidance, and formulation comparisons are covered on the usage and dosage page.

Safety Profile Overview

Erythromycin is generally well tolerated, but its side-effect profile and drug interaction potential are more pronounced than those of newer macrolides. The most common adverse effects are gastrointestinal: nausea, vomiting, abdominal pain, and diarrhea. These occur because erythromycin stimulates motilin receptors in the GI tract — the same mechanism exploited therapeutically in gastroparesis.

Serious but less common adverse effects include QT interval prolongation (with a risk of torsades de pointes, especially when combined with other QT-prolonging drugs), cholestatic hepatitis (most associated with the estolate ester), and ototoxicity at high intravenous doses. Erythromycin is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, creating significant potential for drug interactions with substrates like warfarin, theophylline, carbamazepine, cyclosporine, and certain statins (lovastatin, simvastatin).

Detailed adverse effect data, interaction tables, contraindications, and risk-mitigation guidance are available in the safety section.

Macrolide Comparison

Erythromycin is the first-generation macrolide. The second-generation agents — azithromycin and clarithromycin — were developed to address its limitations: poor GI tolerability, short half-life requiring multiple daily doses, and extensive CYP3A4 interactions.

Despite its disadvantages, erythromycin remains preferred in specific populations (e.g., pregnant patients with chlamydia), in neonatal prophylaxis, and in resource-limited settings where cost and WHO essential-medicine status are deciding factors.

Explore the Full Reference

Additional Topics

• History of erythromycin (1952–present)
• Macrolide drug class overview
• Erythromycin for acne vulgaris
• Erythromycin for gastroparesis
• Drug interaction table
• QT prolongation and cardiac risk
• Erythromycin vs. azithromycin
• Erythromycin vs. clarithromycin