What is the recommended dose of azithromycin (Zithromax) for pneumonia?

Azithromycin Dosing for Pneumonia

For adults with community-acquired pneumonia, azithromycin should be dosed at 500 mg on day 1, followed by 250 mg once daily on days 2-5, but should NOT be used as monotherapy in patients with comorbidities, recent antibiotic use, or in hospitalized patients—these situations require combination therapy with a beta-lactam antibiotic. 1, 2, 3

Adult Outpatient Dosing

Healthy Adults Without Comorbidities

• Standard regimen: 500 mg orally on day 1, then 250 mg once daily on days 2-5 (total 1.5 g over 5 days) 1, 3
• Critical restriction: Use azithromycin monotherapy ONLY in geographic areas where macrolide-resistant Streptococcus pneumoniae is <25% 1, 2
• Alternative 3-day regimen: 500 mg once daily for 3 days (FDA-approved but less commonly used for pneumonia) 3

Adults With Comorbidities or Risk Factors

Azithromycin monotherapy is contraindicated in patients with: 2

• COPD, diabetes, renal failure, heart failure, or malignancy
• Recent antibiotic use within 3 months
• Age >65 years
• Alcoholism, asplenia, or immunosuppression

Required combination therapy: 1, 2

• Amoxicillin 1 g three times daily OR amoxicillin-clavulanate 875 mg/125 mg twice daily (or 2000 mg/125 mg twice daily)
• PLUS azithromycin 500 mg on day 1, then 250 mg daily on days 2-5

Hospitalized Adult Patients

Azithromycin monotherapy is absolutely contraindicated in all hospitalized patients. 2, 4

Mandatory Combination Therapy

• Beta-lactam (ampicillin, ceftriaxone, or cefotaxime) 2
• PLUS azithromycin 500 mg IV or oral daily 4
• Duration: 2-5 days IV, then transition to oral for total 7-10 days 4

Specific Pathogen Coverage

For Legionella pneumonia (hospitalized): 1

• Azithromycin 1000 mg IV on day 1, then 500 mg IV/oral daily
• Alternative: Levofloxacin or moxifloxacin preferred over azithromycin

For Mycoplasma pneumoniae: 1, 4

• Azithromycin 500 mg oral on day 1, then 250 mg daily for 4 days (alternative to doxycycline, which is preferred)

For Chlamydophila pneumoniae: 1

• Azithromycin 500 mg oral on day 1, then 250 mg daily for 4 days

Pediatric Dosing

Standard 5-Day Regimen (Preferred)

For community-acquired pneumonia and atypical pneumonia: 1, 2, 3

• Day 1: 10 mg/kg as single dose (maximum 500 mg)
• Days 2-5: 5 mg/kg once daily (maximum 250 mg per day)
• Total course: 1.5 grams over 5 days

Age-Specific Considerations

Children <5 years old (preschool): 1

• Azithromycin for presumed atypical pneumonia only
• Amoxicillin is preferred for presumed bacterial pneumonia

Children ≥5 years old: 1

• Azithromycin 10 mg/kg day 1 (max 500 mg), then 5 mg/kg daily days 2-5 (max 250 mg)
• May be used as monotherapy for atypical pneumonia
• For bacterial pneumonia, combine with amoxicillin if atypical vs. bacterial distinction unclear

Hospitalized Pediatric Patients

Combination therapy required: 1, 2

• Beta-lactam (ampicillin, ceftriaxone, or cefotaxime)
• PLUS azithromycin (same dosing as outpatient)
• For IV therapy: 10 mg/kg on days 1-2, then transition to oral 2

Alternative Pediatric Regimens

• 3-day regimen: 10 mg/kg once daily for 3 days (for acute bacterial sinusitis and otitis media, not typically used for pneumonia) 3
• Single-dose regimen: 30 mg/kg as single dose (for otitis media only, not pneumonia) 3

Critical Safety Considerations

Cardiac Monitoring

• Obtain baseline ECG in patients with cardiac risk factors before initiating azithromycin 2
• Contraindicate if QTc >450 ms (men) or >470 ms (women) 2
• Monitor when used with other QT-prolonging medications 4

Drug Interactions

• Separate from antacids: Aluminum- or magnesium-containing antacids reduce absorption; separate administration times 4
• Monitor with cytochrome P450-metabolized drugs 4

Renal and Hepatic Impairment

• Renal impairment (GFR <10 mL/min): Use with caution; AUC increases 35% 3
• Hepatic impairment: No specific dose adjustment available; use with caution 3

Treatment Duration and Clinical Response

Expected Response Timeline

• Clinical improvement expected within 48-72 hours 1, 2
• Most patients become afebrile within 48 hours of starting treatment 5
• If no improvement by 48-72 hours, further investigation required 1

Duration Considerations

• Minimum duration: 5 days for standard regimen 2, 3
• Extended duration: May need 7-14 days for atypical pathogens in some cases 1, 2
• Legionella: 7-10 days total 1

Common Pitfalls to Avoid

Critical Errors

1. Using azithromycin monotherapy in patients who received antibiotics in past 3 months (selects for resistance) 2
2. Using monotherapy in areas with macrolide resistance ≥25% 1, 2
3. Using monotherapy in any hospitalized patient (associated with treatment failure) 2
4. Failing to add beta-lactam coverage in patients with comorbidities 1, 2

Resistance Considerations

• Azithromycin's 68-hour half-life creates prolonged subinhibitory concentrations that select for resistant organisms 4
• In areas with high S. pneumoniae resistance, consider alternative agents or mandatory combination therapy 4

Gastrointestinal Tolerance

• Gastrointestinal adverse effects most common but generally mild to moderate 4
• Better GI tolerance than erythromycin 4
• Can be taken with or without food 3