Azithromycin Dosing for Pneumonia
For community-acquired pneumonia, azithromycin is dosed at 500 mg on day 1, followed by 250 mg once daily on days 2-5 (total 1.5g over 5 days) in adults, but should only be used as monotherapy in previously healthy outpatients without comorbidities in areas where pneumococcal macrolide resistance is documented to be less than 25%. 1, 2, 3
Outpatient Treatment Algorithm
Previously Healthy Adults WITHOUT Comorbidities
- Standard azithromycin regimen: 500 mg orally on day 1, then 250 mg once daily on days 2-5 1, 3
- Alternative 3-day regimen: 500 mg once daily for 3 consecutive days (total 1.5g) 3
- Critical restriction: Azithromycin monotherapy is only appropriate when local pneumococcal macrolide resistance is documented to be <25% 1, 2
- Contraindications to monotherapy: Recent antibiotic use within 90 days, any comorbidities, or areas with ≥25% macrolide resistance 1, 2
Adults WITH Comorbidities or Risk Factors
Azithromycin monotherapy is contraindicated. 2, 4 Risk factors include:
- COPD, diabetes, renal failure, heart failure, malignancy 2, 4
- Age >65 years, alcoholism, asplenia, immunosuppression 2, 4
- Recent antibiotic use within 3 months 2, 4
Mandatory combination therapy: 1, 2
- High-dose amoxicillin 1g three times daily OR amoxicillin-clavulanate 875mg/125mg twice daily PLUS azithromycin 500mg day 1, then 250mg daily for days 2-5 1, 2
- Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily for 5 days or moxifloxacin 400mg daily) 1
Hospitalized Patients (Medical Ward)
Azithromycin monotherapy is absolutely contraindicated in hospitalized patients. 2, 4
Mandatory combination therapy: 1, 2
- β-lactam (ampicillin-sulbactam 1.5-3g every 6 hours, ceftriaxone 1-2g daily, or cefotaxime 1-2g every 8 hours) PLUS azithromycin 500mg daily 1, 2
- Continue until clinical stability achieved (afebrile for 48-72 hours with no more than one sign of clinical instability) 2
Severe CAP (ICU Patients)
Combination therapy is mandatory: 2
- β-lactam PLUS azithromycin 500mg daily (strong recommendation, moderate quality evidence) 2
- Alternative: β-lactam PLUS respiratory fluoroquinolone 2
Pediatric Dosing (≥6 months)
- Day 1: 10 mg/kg as single dose (maximum 500mg) 4, 3
- Days 2-5: 5 mg/kg once daily (maximum 250mg per day) 4, 3
- Total course: 1.5 grams over 5 days 4, 3
Alternative 3-day regimen: 3
- 10 mg/kg once daily for 3 days 3
For infants <6 months: 5
- 10 mg/kg per day for 5 days 5
Treatment Duration and Clinical Response
- Minimum duration: 5 days for standard regimen 1, 2
- Clinical improvement expected: Fever should resolve within 48-72 hours 2
- Extended therapy (10-14 days): Only for atypical pathogens (Mycoplasma, Chlamydophila, Legionella) if clinically indicated 2, 4
- Severe infections requiring 14-21 days: Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli 1
Critical Safety Considerations
Before initiating azithromycin: 2
- Obtain ECG to assess QTc interval in patients with cardiac risk factors 2
- Contraindicate if: QTc >450ms for men or >470ms for women 2
Common adverse effects: 3
- Do not take simultaneously with aluminum- or magnesium-containing antacids (reduces absorption) 5
- Monitor when used with digoxin, triazolam, ergot alkaloids, or drugs metabolized by cytochrome P450 5
Common Pitfalls to Avoid
Never use azithromycin monotherapy in patients with any comorbidities - this is associated with breakthrough pneumococcal bacteremia and clinical failure 1, 2
Never use azithromycin monotherapy in hospitalized patients - combination with β-lactam is mandatory 2, 4
Do not use in areas with ≥25% macrolide resistance - 20-30% of S. pneumoniae isolates show macrolide resistance in many regions, leading to clinical failures 2
Avoid in patients with recent antibiotic exposure (within 3 months) - selects for resistant organisms 2, 4
Do not automatically extend duration beyond 5 days - reassess for alternative diagnoses or complications rather than reflexively prolonging antibiotics 1