Azithromycin Dosing and Treatment Duration
Azithromycin dosing varies significantly by indication, with the most common adult regimen being 500 mg on day 1 followed by 250 mg daily for days 2-5 (total 1.5 g), though sexually transmitted infections require a single 1 gram dose for optimal compliance. 1
Standard Adult Dosing by Indication
Respiratory Tract Infections
- Community-acquired pneumonia (mild): 500 mg on day 1, then 250 mg once daily on days 2-5 1
- Acute bacterial exacerbations of COPD: Either 500 mg daily for 3 days OR 500 mg on day 1, then 250 mg daily on days 2-5 1
- Acute bacterial sinusitis: 500 mg daily for 3 days 1
- Pharyngitis/tonsillitis (second-line): 500 mg on day 1, then 250 mg daily on days 2-5 1
Important caveat: Azithromycin is not first-line for streptococcal pharyngitis due to variable macrolide resistance and should only be used in penicillin-allergic patients 2
Sexually Transmitted Infections
- Non-gonococcal urethritis/cervicitis (Chlamydia): Single 1 gram dose 1, 3
- Gonococcal urethritis/cervicitis: Single 2 gram dose 1
- Chancroid (genital ulcer disease): Single 1 gram dose 1
The single-dose regimen is critical for compliance and allows directly observed therapy, particularly important in populations unlikely to return for follow-up 3. Patients must abstain from sexual intercourse for 7 days after completing therapy 3.
Skin and Soft Tissue Infections
- Uncomplicated infections: 500 mg on day 1, then 250 mg daily on days 2-5, with total duration approximately 7 days depending on clinical response 1, 4
Special Respiratory Conditions
- Legionnaires' disease (hospitalized): 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 2
- Legionnaires' disease (non-hospitalized): 500 mg on day 1, then 250 mg daily for 4 additional days 2
Long-Term Prophylactic Regimens
- Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly for minimum 6-12 months 3, 5
- Alternative: 250 mg daily 3
- Bronchiolitis obliterans syndrome (lung transplant): 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months 3
- MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 3
- Disseminated MAC disease in AIDS: 250 mg daily with ethambutol, with or without rifabutin 3
Pediatric Dosing by Indication
Respiratory Tract Infections
- Acute otitis media: Three options 1:
- Single 30 mg/kg dose (1-day regimen)
- 10 mg/kg once daily for 3 days (3-day regimen)
- 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 (5-day regimen)
- Acute bacterial sinusitis: 10 mg/kg once daily for 3 days 1
- Community-acquired pneumonia: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1
- Pharyngitis/tonsillitis: 12 mg/kg once daily for 5 days (ages ≥2 years) 1
The higher 12 mg/kg dose for pharyngitis is necessary to prevent recurrence, which occurs more frequently with standard dosing compared to penicillin 6.
Atypical Pathogens (Mycoplasma, Chlamydia pneumoniae)
- 10 mg/kg on days 1-2, then transition to oral OR 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 2
Pertussis
- Infants <6 months: 10 mg/kg daily for 5 days 3
- Infants and children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg daily (max 250 mg) on days 2-5 3
Special Pediatric Conditions
- Cat scratch disease (≥45 kg): 500 mg on day 1, then 250 mg for 4 additional days 3
- Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg for 4 more days 3
- Chlamydial conjunctivitis (neonates): 20 mg/kg daily for 3 days 3
Administration and Drug Interactions
- Can be taken with or without food 1
- Avoid concurrent aluminum or magnesium-containing antacids as they reduce absorption 3
- If taken with a large meal, absorption may be reduced by up to 50% 7
Cardiac Safety Monitoring
Before initiating azithromycin, obtain an ECG in patients with cardiac risk factors to assess QTc interval 5, 2. This is particularly critical for:
- Long-term therapy regimens 3
- Patients taking other QT-prolonging medications 3
- Elderly patients with cardiac disease 5
Contraindications based on QTc:
Renal and Hepatic Dosing
- Renal impairment (GFR 10-80 mL/min): No dosage adjustment needed 1
- Severe renal impairment (GFR <10 mL/min): Use with caution; AUC increases 35% 1
- Hepatic impairment: No established dosing recommendations; pharmacokinetics not studied 1
Common Adverse Effects
- Gastrointestinal: Diarrhea, abdominal pain, nausea, vomiting (generally mild to moderate) 3, 5
- Incidence: Approximately 3% experience nausea/vomiting 5
- Better tolerated than erythromycin with fewer GI side effects 6, 7
Critical Resistance and Stewardship Considerations
Azithromycin's 68-hour half-life creates a prolonged "window" of subinhibitory concentrations (14-20 days for complete elimination), which may promote selection of resistant organisms 4. This is particularly concerning for:
- Streptococcus pneumoniae (carriage rates of resistant strains increased to 55% at 2-3 weeks post-treatment in one study) 4
- Group A streptococcus (geographically variable resistance) 2
Never use azithromycin as monotherapy for gonorrhea due to widespread resistance; always combine with ceftriaxone if gonococcal infection suspected 3.
Monitoring for Long-Term Therapy
- Baseline liver function tests before initiating chronic therapy 3
- Baseline ECG for QTc assessment 3
- Minimum 6-month duration required to demonstrate benefit in bronchiectasis 3
- Assess clinical response at days 5-7 for acute infections 5
Pregnancy and Pediatric Safety
- FDA Pregnancy Category B 3
- Preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3
- Safety of re-dosing after vomiting: Not established for the 30 mg/kg single-dose regimen, though 8 patients in clinical trials were successfully re-dosed at the same total dose after vomiting within 30 minutes 1