What are the appropriate indications for azithromycin use in infants?

Azithromycin Indications in Infants

FDA-Approved Indications (≥6 Months)

For infants 6 months and older, azithromycin is FDA-approved for acute otitis media, acute bacterial sinusitis, and community-acquired pneumonia. 1

• Acute otitis media: Three dosing options are available: (1) 30 mg/kg as a single dose, (2) 10 mg/kg once daily for 3 days, or (3) 10 mg/kg on day 1 followed by 5 mg/kg daily on days 2–5. 1

• 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 once daily on days 2–5 (5-day regimen). 1 This regimen is specifically indicated for atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Chlamydia trachomatis. 2

• Pharyngitis/tonsillitis (≥2 years): 12 mg/kg once daily for 5 days is required due to high recurrence rates with standard dosing; however, penicillin or amoxicillin remain first-line agents. 2, 1

CDC-Recommended Indications (<6 Months, Off-Label)

Despite lack of FDA licensure in infants younger than 6 months, the CDC explicitly recommends azithromycin as the preferred first-line agent for pertussis treatment and post-exposure prophylaxis in this age group because the benefits outweigh potential risks. 3, 4

Pertussis Treatment and Prophylaxis

• Infants <1 month: Azithromycin 10 mg/kg once daily for 5 days is strongly preferred over erythromycin, which carries a 5–10% absolute risk of infantile hypertrophic pyloric stenosis (IHPS). 3

• Infants 1–5 months: Azithromycin 10 mg/kg once daily for 5 days (first-line) or clarithromycin 15–20 mg/kg/day divided twice daily for 7 days (alternative). 3

• Infants ≥6 months: Azithromycin 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily on days 2–5. 2, 3

• All infants receiving any macrolide should be monitored for IHPS symptoms (non-bilious vomiting, feeding-related irritability), although azithromycin has not been associated with IHPS. 2, 3

Timing and Effectiveness

• Early treatment during the catarrhal phase (first ≈2 weeks) rapidly eradicates Bordetella pertussis from the nasopharynx and reduces coughing paroxysms by approximately 50%. 3, 4

• In the paroxysmal phase (>3 weeks from cough onset), clinical benefit to the patient is minimal, but treatment remains essential to eliminate the organism and prevent transmission. 3, 4

Post-Exposure Prophylaxis Priority Groups

Prophylaxis uses the same dosing regimens as treatment and should be administered within 21 days of exposure to: 3

• All household and close contacts, regardless of vaccination status
• Infants <12 months (especially <4 months)—highest risk of severe/fatal disease
• Pregnant women in the third trimester
• Healthcare workers with documented exposure
• Child-care workers who have contact with infants

Indications Where Azithromycin Should NOT Be Used

Azithromycin should not be used as first-line therapy for typical bacterial pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae; amoxicillin at 90 mg/kg/day remains the preferred agent. 2

Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis, as multiple randomized controlled trials demonstrate no benefit in length of stay, oxygen requirement, or readmission rates. 5, 6, 7

For streptococcal pharyngitis, azithromycin is second-line therapy only; penicillin or amoxicillin remain first-line due to superior outcomes and lower recurrence rates. 2

Special Populations

HIV-Infected Infants

• Mycobacterium avium complex (MAC) prophylaxis: 20 mg/kg once weekly (maximum 1,200 mg per dose). 2

Critical Administration Considerations

• Azithromycin must not be taken simultaneously with aluminum- or magnesium-containing antacids; doses should be separated by at least 2 hours because antacids reduce absorption. 2, 3

• Azithromycin can be taken with or without food. 1

• For IV administration (when parenteral therapy is required for atypical pneumonia): 10 mg/kg once daily (maximum 500 mg) on days 1–2, then transition to oral therapy as soon as clinically feasible. 2

Expected Clinical Response and Red Flags

Children on appropriate azithromycin therapy should demonstrate clinical improvement within 48–72 hours. 2

If no improvement or clinical deterioration occurs within this timeframe, reassess for: 2

• Incorrect diagnosis or resistant pathogens
• Complications such as parapneumonic effusion
• Need for alternative or additional antimicrobial therapy

Safety Monitoring

• Common adverse effects include gastrointestinal disturbances (abdominal discomfort, diarrhea, nausea, vomiting), dizziness, and headache. 2, 3

• For prolonged courses (e.g., non-tuberculous mycobacterial infection), obtain baseline ECG, repeat at 2 weeks, and after adding any QT-prolonging medication. 2

• Azithromycin does NOT inhibit cytochrome P450 enzymes, unlike erythromycin and clarithromycin. 3

Absolute Contraindications

• Macrolides are absolutely contraindicated in individuals with known hypersensitivity to any macrolide. 3

• Trimethoprim-sulfamethoxazole (the alternative for macrolide-intolerant patients >2 months) is absolutely contraindicated in infants <2 months due to kernicterus risk. 3

• Clarithromycin should not be given to infants <1 month due to concerns about IHPS association. 3