Introduction
Erythromycin is a macrolide antibiotic first isolated in 1952 from the bacterium Streptomyces erythreus. It represents one of the earliest macrolide antibiotics and has served as a fundamental antimicrobial agent for decades. Erythromycin demonstrates activity against a broad spectrum of Gram-positive and some Gram-negative bacteria, as well as certain atypical pathogens. It remains clinically relevant despite the development of newer macrolides due to its established efficacy profile and various formulations.
Mechanism of Action
Erythromycin exerts its antibacterial effect by binding to the 50S ribosomal subunit of susceptible microorganisms, thereby inhibiting bacterial protein synthesis. Specifically, it blocks the translocation step wherein newly synthesized peptidyl-tRNA moves from the ribosomal A-site to the P-site. This bacteriostatic action prevents bacterial replication without directly causing cell death. At higher concentrations, particularly against highly susceptible organisms, erythromycin may demonstrate bactericidal activity.
Indications
FDA-approved indications include:
- Upper and lower respiratory tract infections (pharyngitis, tonsillitis, bronchitis, pneumonia)
- Skin and soft tissue infections
- Pertussis (whooping cough) prophylaxis and treatment
- Diphtheria (as adjunct to antitoxin)
- Erythrasma
- Intestinal amebiasis
- Campylobacter gastroenteritis
- Legionnaires' disease
- Syphilis (in penicillin-allergic patients)
- Chlamydia infections
Non-FDA approved uses include:
- Prokinetic agent for gastroparesis
- Post-operative ileus prevention
- Rosacea management
Dosage and Administration
Adults:- Base: 250-500 mg orally every 6-12 hours
- Ethylsuccinate: 400-800 mg orally every 6-12 hours
- IV: 15-20 mg/kg/day divided every 6 hours (max 4 g/day)
- 30-50 mg/kg/day divided every 6-8 hours orally
- IV: 20-40 mg/kg/day divided every 6 hours
- Renal impairment: No dosage adjustment typically needed
- Hepatic impairment: Use with caution; consider dose reduction
- Elderly: Monitor for QT prolongation and hepatic function
- Oral forms should be administered on an empty stomach (1 hour before or 2 hours after meals)
- IV formulation must be administered by continuous infusion over 20-60 minutes
- Do not administer with fruit juices or acidic beverages which may degrade the drug
Pharmacokinetics
Absorption: Variable depending on salt form (20-65% bioavailability); affected by food Distribution: Widely distributed to body tissues and fluids; crosses placenta; enters breast milk Protein Binding: Approximately 70-90% Metabolism: Primarily hepatic via demethylation; active metabolites formed Elimination: Mostly biliary excretion (2-5% renal excretion) Half-life: 1.5-2 hours (prolonged in hepatic impairment)Contraindications
- Known hypersensitivity to erythromycin or other macrolides
- Concomitant use with drugs that prolong QT interval (cisapride, pimozide, terfenadine)
- History of cholestatic jaundice/hepatic dysfunction with previous erythromycin use
- Patients with known hypokalemia or hypomagnesemia
Warnings and Precautions
- QT prolongation and torsades de pointes: Monitor ECG in at-risk patients
- Hepatotoxicity: May cause cholestatic jaundice; monitor LFTs
- Clostridium difficile-associated diarrhea: May range from mild to life-threatening
- Hearing loss: Reversible with discontinuation, mostly with high doses
- Myasthenia gravis exacerbation: May worsen muscle weakness
- Superinfection: May result in bacterial or fungal overgrowth
Drug Interactions
Major Interactions:- CYP3A4 inhibitors: Increased erythromycin concentrations
- CYP3A4 substrates: Erythromycin inhibits metabolism of numerous drugs including:
- Statins (increased risk of rhabdomyolysis) - Benzodiazepines (increased sedation) - Warfarin (increased INR) - Digoxin (increased concentrations) - Theophylline (increased concentrations)
- Drugs that prolong QT interval: Additive risk of torsades de pointes
Adverse Effects
Common (≥1%):- Nausea, vomiting, abdominal pain, diarrhea
- Anorexia
- Rash
- Injection site reactions (IV formulation)
- QT prolongation/torsades de pointes
- Hepatotoxicity (cholestatic jaundice, hepatitis)
- Pseudomembranous colitis
- Stevens-Johnson syndrome
- Reversible hearing loss
- Ventricular arrhythmias
Monitoring Parameters
- Clinical response to therapy
- Signs of superinfection
- Liver function tests (baseline and periodically)
- ECG in patients with cardiac risk factors or receiving high doses
- Serum concentrations of co-administered drugs with narrow therapeutic indices
- Serum electrolytes in patients at risk for QT prolongation
- Hearing function with prolonged high-dose therapy
Patient Education
- Complete the full course of therapy even if feeling better
- Take on empty stomach with full glass of water
- Report severe diarrhea, abdominal pain, or bloody stools
- Notify provider of any hearing changes, dizziness, or palpitations
- Avoid excessive sun exposure due to photosensitivity risk
- Inform all healthcare providers of erythromycin use due to interaction potential
- Do not crush or chew delayed-release formulations
- Store at room temperature away from moisture
References
1. FDA Prescribing Information: Erythromycin (Various Formulations) 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 3. Lexicomp Online. Erythromycin Monograph. 4. Thorne Pharmaceuticals. Erythromycin Product Information. 5. Zuckerman JM, et al. Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin North Am. 2004;18(3):621-649. 6. Periti P, et al. Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet. 1992;23(2):106-131. 7. Ray WA, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089-1096. 8. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Erythromycin.