What is the recommended dosage of azithromycin (Zithromax) for community-acquired pneumonia (CAP)?

Azithromycin Dosing for Community-Acquired Pneumonia

For outpatient adults with CAP, azithromycin should be dosed at 500 mg on day 1, followed by 250 mg once daily on days 2-5, or alternatively 500 mg once daily for 3 days. 1

Outpatient Adult Dosing

Standard Regimen

• 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2-5 (total 5-day course) 1
• Alternative: 500 mg once daily for 3 days 1
• Both regimens can be taken with or without food 1

Clinical Context for Use

• Azithromycin is appropriate for presumed atypical pneumonia in outpatients ≥5 years old 2
• For children <5 years with presumed atypical pneumonia: 10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2-5 2
• For children ≥5 years with presumed atypical pneumonia: 10 mg/kg on day 1 (max 500 mg), followed by 5 mg/kg/day (max 250 mg) on days 2-5 2

Important Prescribing Considerations

When to Use Azithromycin Alone vs. Combination Therapy

• Macrolide monotherapy should NOT be used in areas with pneumococcal macrolide resistance ≥25% 3
• For patients with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancies; asplenia), azithromycin should be combined with a β-lactam (amoxicillin/clavulanate or cephalosporin), not used as monotherapy 3
• Avoid using azithromycin if the patient received antibiotics from the same class in the previous 3 months due to resistance risk 4

Inpatient Use

• For hospitalized non-ICU patients: azithromycin is used in combination with a β-lactam (ampicillin/sulbactam, ceftriaxone, cefotaxime, or ceftaroline) 2
• The inpatient dosing is typically the same as outpatient (500 mg day 1, then 250 mg daily), though IV formulations may be used initially 2

Treatment Duration and Expected Response

Duration

• Standard treatment is 5 days total (500 mg day 1, then 250 mg days 2-5) 1
• The 3-day regimen (500 mg daily × 3 days) is FDA-approved and equally effective 1, 5
• For atypical pathogens (Mycoplasma, Chlamydophila): 10-14 days may be needed, though azithromycin's prolonged tissue half-life (11-14 hours) means the 5-day oral course provides extended antimicrobial activity 2
• For Legionella pneumonia: 10-14 days of therapy is recommended 2

Expected Clinical Response

• Patients should show clinical improvement within 48-72 hours of initiating appropriate therapy 2
• If no improvement or clinical deterioration occurs within 48-72 hours, further investigation is warranted 2

Special Populations

Renal Impairment

• No dosage adjustment needed for GFR ≥10 mL/min 1
• For GFR <10 mL/min, AUC increases 35%; use with caution in severe renal impairment 1

Hepatic Impairment

• Pharmacokinetics not established in hepatic impairment; no specific dose adjustment recommendations available 1

Pediatric Dosing

• Community-acquired pneumonia: 10 mg/kg day 1 (max 500 mg), then 5 mg/kg days 2-5 (max 250 mg/day) 1
• Acute otitis media: 30 mg/kg as single dose, OR 10 mg/kg once daily × 3 days, OR 10 mg/kg day 1 then 5 mg/kg days 2-5 1

Clinical Efficacy Evidence

Effectiveness Against Resistant Organisms

• Azithromycin demonstrates clinical efficacy even against macrolide-resistant S. pneumoniae in some studies, with 76.5% clinical success despite 85.7% in vitro resistance 6
• However, this finding should be interpreted cautiously—clinical failure can occur with macrolide-resistant isolates, particularly in high-risk patients 4
• The discordance between in vitro resistance and clinical outcomes may relate to azithromycin's high tissue concentrations and immunomodulatory effects 6

Comparative Efficacy

• Single 2-gram dose of azithromycin microspheres showed 92.6% clinical cure rate, comparable to 7-day clarithromycin extended-release (94.7%) 7
• Three-day azithromycin 1g daily demonstrated 92.6% clinical success, non-inferior to 7-day amoxicillin-clavulanate (93.1%) 5
• Standard 3-day azithromycin course achieved 98% satisfactory clinical response in moderately severe CAP 8

Common Pitfalls to Avoid

• Do not use azithromycin monotherapy for patients with risk factors for drug-resistant S. pneumoniae (age >65, recent antibiotic use, comorbidities, immunosuppression) 4, 3
• Do not use in areas with high local pneumococcal macrolide resistance (≥25%) without combination therapy 3
• Do not assume the 3-day or 5-day course is insufficient—azithromycin's prolonged tissue half-life provides extended antimicrobial activity beyond the dosing period 2
• Do not overlook the need for combination therapy in hospitalized patients—azithromycin should be paired with a β-lactam for adequate pneumococcal coverage 2