What is the recommended dose of azithromycin (macrolide antibiotic) for community-acquired pneumonia?

Azithromycin Dosing for Community-Acquired Pneumonia

For outpatient community-acquired pneumonia, azithromycin should be dosed as 500 mg on day 1, followed by 250 mg once daily on days 2-5 (total 1.5g over 5 days), but only as monotherapy in previously healthy patients without comorbidities in areas where macrolide-resistant S. pneumoniae is <25%. 1, 2

Outpatient Treatment Algorithm

Previously Healthy Patients (No Comorbidities)

• Azithromycin monotherapy is acceptable at 500 mg on day 1, then 250 mg daily for days 2-5 1, 2
• Alternative dosing: 500 mg once daily for 3 days (total 1.5g) 3, 2
• Critical restriction: Only use monotherapy in regions with macrolide resistance <25% 1
• Do not use if patient received antibiotics within the past 3 months 1

Patients WITH Comorbidities or Risk Factors

Azithromycin monotherapy is contraindicated in patients with: 1

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

For these patients, use combination therapy: 1

• High-dose amoxicillin (1g three times daily) OR amoxicillin-clavulanate (2g twice daily) PLUS azithromycin 500 mg daily
• Alternative: Respiratory fluoroquinolone alone (levofloxacin 750mg or moxifloxacin 400mg)

Hospitalized Patients (Medical Ward)

Azithromycin monotherapy is never appropriate for hospitalized patients. 1

Mandatory combination therapy: 3, 1

• β-lactam (ampicillin-sulbactam 1.5-3g q6h, ceftriaxone 1-2g daily, or cefotaxime 1-2g q8h) PLUS azithromycin 500 mg daily
• Alternative from European guidelines: IV or oral azithromycin 500 mg daily for 3 days or 500 mg day 1 then 250 mg daily for 5 days, always with a β-lactam 3

ICU/Severe Pneumonia

Combination therapy is mandatory with moderate-to-strong evidence: 1

• β-lactam PLUS azithromycin 500 mg daily, OR
• β-lactam PLUS respiratory fluoroquinolone

Treatment Duration

Minimum duration: 5 days, with patient afebrile for 48-72 hours and no more than one sign of clinical instability before discontinuation 1

Extended duration considerations: 1

• Atypical pathogens (Mycoplasma, Chlamydophila): May require 10-14 days
• Initial therapy not active against identified pathogen: Extend duration
• Complicated by extrapulmonary infection: Extend duration
• Maximum for responding patients: Generally should not exceed 8 days 1

Critical Safety Considerations

Before initiating therapy: 1

• Obtain ECG in patients with cardiac risk factors to assess QTc interval
• Avoid azithromycin if QTc >450ms (men) or >470ms (women)

Common Pitfalls to Avoid

1. Do not use azithromycin monotherapy in areas with ≥25% macrolide resistance—clinical failures occur with resistant S. pneumoniae isolates requiring hospitalization and β-lactam rescue therapy 1

2. Do not use monotherapy in patients who received antibiotics in the past 3 months, as this selects for resistant organisms 1

3. Never use monotherapy in hospitalized patients—combination therapy is the standard of care 1

4. Do not use monotherapy in elderly patients (>65 years) or those with any comorbidities—these patients require combination therapy 1