Azithromycin
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azithromycin mechanism of action pharmacology spectrum
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azithromycin clinical indications dosing adverse effects drug interactions
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Azithromycin
Drug Class & Mechanism
Azithromycin is a macrolide antibiotic (azalide subclass). It binds reversibly to the 50S ribosomal subunit (23S rRNA), blocking translocation and inhibiting bacterial protein synthesis. It is primarily bacteriostatic but can be bactericidal at high concentrations against certain organisms.
Antimicrobial Spectrum
| Category | Covered Organisms |
|---|---|
| Gram-positive | S. aureus (MSSA), S. pneumoniae, S. pyogenes |
| Atypical/intracellular | Mycoplasma pneumoniae, Chlamydia spp., Legionella pneumophila, Chlamydophila pneumoniae |
| Gram-negative | H. influenzae, M. catarrhalis, N. gonorrhoeae |
| Other | Bordetella pertussis, Borrelia burgdorferi, Treponema pallidum (limited), Mycobacterium avium complex (MAC) |
Not covered: MRSA, Pseudomonas, Enterobacteriaceae (poor activity), anaerobes.
Pharmacokinetics
| Parameter | Detail |
|---|---|
| Bioavailability | ~37% oral |
| Half-life | ~68 hours (tissue half-life even longer) |
| Distribution | Extensive; high tissue concentrations (lung, tonsil, cervix); low serum levels |
| Metabolism | Minimal hepatic (minimal CYP450 interaction — key advantage over clarithromycin) |
| Elimination | Primarily biliary/fecal |
The long tissue half-life allows for short-course regimens (e.g., 5-day Z-pack, single-dose for chlamydia).
Clinical Indications & Dosing
| Indication | Dose |
|---|---|
| Community-acquired pneumonia (outpatient) | 500 mg day 1, then 250 mg days 2–5 |
| Chlamydial urethritis/cervicitis | 1 g single dose |
| Gonorrhea (with ceftriaxone) | 1 g single dose (declining role due to resistance) |
| Pharyngitis (penicillin allergy) | 500 mg day 1, then 250 mg days 2–5 |
| MAC prophylaxis (HIV, CD4 <50) | 1200 mg once weekly |
| MAC treatment (NTM pulmonary disease) | 250–500 mg daily (combination regimen) |
| Pertussis (post-exposure/treatment) | 500 mg day 1, then 250 mg days 2–5 |
| Traveler's diarrhea | 500 mg daily × 3 days |
| Acne vulgaris | Not preferred (doxycycline is favored; azithromycin promotes resistance) |
Adverse Effects
- GI: Nausea, diarrhea, abdominal cramps (most common, though less than erythromycin)
- Cardiac: QTc prolongation and risk of torsades de pointes — caution with concurrent QT-prolonging drugs, hypokalemia, hypomagnesemia (Treatment of NTM Pulmonary Disease, p. 14)
- Hepatotoxicity: Cholestatic jaundice (rare)
- Hearing loss: Reported at higher doses (≥600 mg/day), particularly in older patients (Treatment of NTM Pulmonary Disease, p. 14)
- Hypersensitivity: Rash, angioedema (rare)
Drug Interactions
Azithromycin has fewer CYP450-mediated interactions than clarithromycin (a key clinical advantage), but still interacts with:
- QT-prolonging drugs (amiodarone, fluoroquinolones, antipsychotics, TCAs) — additive QTc prolongation risk
- Antacids (Al/Mg) — reduce peak serum levels (separate by 2 hours)
- Warfarin — may potentiate anticoagulant effect
Special Populations
| Population | Consideration |
|---|---|
| Pregnancy | Category B; generally considered safe |
| Renal impairment | No dose adjustment needed |
| Hepatic impairment | Use with caution; avoid in severe liver disease |
| Elderly | Higher risk of QTc prolongation and hearing loss at elevated doses |
| Pediatrics | Approved; used for otitis media, pharyngitis, CAP |
Resistance
- Resistance occurs via 23S rRNA methylation (erm genes) and efflux pumps (mef genes).
- Growing resistance in S. pneumoniae and S. pyogenes limits its use in some regions.
- Increasing azithromycin use in acne treatment has raised resistance concerns (Management of Acne Vulgaris, p. 11).
Key Clinical Pearls
- Preferred over clarithromycin for MAC treatment due to better tolerability, fewer drug interactions, once-daily dosing, and lower pill burden (Treatment of NTM Pulmonary Disease, p. 14).
- Its long tissue half-life enables single-dose and short-course therapy.
- Always assess baseline QTc before use in high-risk patients.
- Not a first-line agent for acne — doxycycline is preferred to minimize resistance selection.
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