What is the dosage and treatment duration of Azithromycin for various bacterial infections?

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 on days 2-5 for respiratory infections, while sexually transmitted infections typically require a single 1-gram dose. 1

Standard Adult Dosing Regimens

Respiratory Tract Infections

• Community-acquired pneumonia (mild): 500 mg on day 1, then 250 mg once daily on days 2-5 (total 5 days) 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 once daily for 3 days 1
• Upper respiratory infections: 500 mg daily for 3 days or the standard 5-day regimen 2

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (Chlamydia): Single 1-gram dose 1, 3
  • This single-dose regimen provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 3
  • The critical advantage is improved compliance and allows for directly observed therapy 3
• Gonococcal urethritis/cervicitis: Single 2-gram dose 1
  • Important caveat: Do not use azithromycin as monotherapy for gonorrhea due to widespread resistance; combine with ceftriaxone for suspected gonococcal infection 3
• Genital ulcer disease (chancroid): Single 1-gram dose 1

Other Infections

• Pharyngitis/tonsillitis (second-line): 500 mg on day 1, then 250 mg daily on days 2-5 1
  • Critical pitfall: Azithromycin is not first-line for strep pharyngitis due to variable macrolide resistance; reserve for penicillin-allergic patients 4
• Skin/soft tissue infections (uncomplicated): 500 mg on day 1, then 250 mg daily on days 2-5 1

Chronic Respiratory Conditions (Long-term Therapy)

• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly, requiring 6-12 months to demonstrate benefit 3
• Asthma with frequent exacerbations: 500 mg three times weekly or 250 mg daily for 6-12 months 3

Specialized Indications

• Cat scratch disease (>45 kg): 500 mg on day 1, then 250 mg daily for 4 additional days 3
• Legionnaires' disease (hospitalized): 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 4
• Legionnaires' disease (non-hospitalized): 500 mg on day 1, then 250 mg daily for 4 days 4
• Disseminated MAC disease in AIDS: 250 mg daily with ethambutol, with or without rifabutin 3
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 3
• Travelers' diarrhea with dysentery: Single 1-gram dose or 500 mg daily for 3 days 2

Pediatric Dosing Regimens

Standard Pediatric Dosing (≥6 months)

• Acute otitis media: Three options available 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 (≥2 years): 12 mg/kg once daily for 5 days 1

Atypical Pneumonia Pathogens

• Mycoplasma pneumoniae, Chlamydia trachomatis, or Chlamydophila pneumoniae: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 4

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 Populations

• Chlamydial conjunctivitis in neonates: 20 mg/kg once daily for 3 days 3
• Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg daily for 4 days 3

Administration Considerations

• Food interactions: Can be taken with or without food 1
• Antacid interactions: Avoid concurrent administration with aluminum or magnesium-containing antacids as absorption may be reduced 3
• Directly observed therapy: Dispense medication on-site when possible and observe first dose to maximize compliance, particularly for STI treatment 3

Cardiac Safety Monitoring

Before initiating azithromycin, obtain an ECG in patients with cardiac risk factors to assess QTc interval. 3, 4

• Contraindication: QTc >450 ms (men) or >470 ms (women) 3, 2, 4
• Mechanism: Azithromycin can prolong QTc interval, increasing risk of torsades de pointes 3
• High-risk patients: Those with prolonged QTc, electrolyte abnormalities, or taking other QT-prolonging medications require careful risk assessment 3

Hepatic and Renal Considerations

• Renal impairment (GFR ≤80 mL/min): No dosage adjustment needed 1
• Severe renal impairment (GFR <10 mL/min): Exercise caution; AUC increases 35% compared to normal function 1
• Hepatic impairment: No established dosage adjustments; pharmacokinetics not well-studied 1
• Baseline monitoring for long-term therapy: Obtain liver function tests 3

Common Adverse Effects

• Gastrointestinal symptoms: Nausea, diarrhea, abdominal pain/discomfort, vomiting (most common) 3
  • Incidence approximately 3% in gastrointestinal infections 2
  • Better tolerated than erythromycin 5, 6
• Other effects: Headache, dizziness 3

Critical Antimicrobial Stewardship Considerations

Resistance Concerns

Azithromycin's prolonged tissue half-life (68 hours) creates an extended "window" of subinhibitory drug concentrations lasting 14-20 days, which may promote selection of resistant organisms. 7

• Pneumococcal resistance: Studies show carriage rates of azithromycin-resistant S. pneumoniae increased from 2% pre-treatment to 55% at 2-3 weeks, declining to 6% at 6 months 7
• Geographic variation: Macrolide resistance varies significantly by region and over time, particularly for group A streptococcus 4

Stewardship Principles

• Limit antibiotic exposure: Use shortest effective duration 2, 4
• Consider viral etiology: Many respiratory infections are viral and do not require antibiotics 2, 4
• Assess clinical response: Evaluate improvement at days 5-7 2
• Avoid inappropriate use: Not first-line for strep pharyngitis or gonorrhea monotherapy 3, 4

Pharmacodynamic Properties

• Mechanism: Time-dependent killing with moderate to prolonged persistent effects 7
• Key parameter: AUC to MIC ratio (target approximately 25 for maximal efficacy) rather than time above MIC 7
• Tissue distribution: Extensive tissue penetration with concentrations exceeding serum levels; volume of distribution 23 L/kg 6, 8
• Terminal half-life: Up to 5 days, allowing once-daily or single-dose regimens 6, 8

Special Clinical Situations

• Pregnancy: FDA Category B 3
• Infants <1 month: Preferred over erythromycin due to lower risk of infantile hypertrophic pyloric stenosis 3
• Lyme disease (early localized, intolerant of first-line): 500 mg daily for 7-10 days with close observation 3
• Sexual abstinence after STI treatment: Patients should abstain for 7 days after completing therapy 3