What is the appropriate use and dosage of Azithromycin (macrolide antibiotic) for pediatric patients with bacterial infections?

Azithromycin for Pediatric Bacterial Infections

Azithromycin is dosed at 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg (maximum 250 mg) once daily for days 2-5 for most pediatric respiratory infections, but it should be reserved primarily for atypical pathogens (Mycoplasma, Chlamydia) rather than typical bacterial infections where amoxicillin remains first-line. 1, 2

Indication-Specific Dosing

Community-Acquired Pneumonia (Atypical Pathogens)

• Standard 5-day regimen: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily for days 2-5 1, 2
• Specifically indicated for Mycoplasma pneumoniae, Chlamydia pneumoniae, and Chlamydia trachomatis in children ≥6 months 1, 3
• Critical caveat: Amoxicillin (90 mg/kg/day) remains the preferred first-line agent for typical bacterial pneumonia caused by S. pneumoniae or H. influenzae 2, 4
• For children ≥5 years where bacterial versus atypical etiology cannot be distinguished clinically, add azithromycin to a β-lactam antibiotic 2

Pertussis Treatment and Prophylaxis

• Infants <6 months: 10 mg/kg once daily for 5 days 1, 3
• Children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily for days 2-5 1, 3
• Azithromycin is preferred over erythromycin due to better safety profile, especially in young infants 1
• Important safety note: In infants <1 month, azithromycin has not been associated with infantile hypertrophic pyloric stenosis (IHPS), though monitoring is recommended 1

Streptococcal Pharyngitis/Tonsillitis

• Azithromycin is second-line therapy only—penicillin or amoxicillin remain first-line 1, 2
• Higher dose required: 12 mg/kg once daily for 5 days (maximum 500 mg/day) due to high recurrence rates with standard dosing 1, 5
• Standard 10 mg/kg regimen results in more recurrences compared to penicillin 6

Acute Otitis Media

• Three dosing options per FDA labeling: 5
  • Single 30 mg/kg dose (maximum 1500 mg)
  • 10 mg/kg once daily for 3 days
  • 10 mg/kg on day 1, then 5 mg/kg daily for days 2-5
• Single-dose regimen shows 88% end-of-treatment clinical success but lower efficacy against macrolide-resistant S. pneumoniae (67% vs 90% for susceptible strains) 7

Acute Bacterial Sinusitis

• 10 mg/kg once daily for 3 days 5

Chlamydial Infections (Adolescents)

• Single 1 gram oral dose for uncomplicated urethritis or cervicitis caused by Chlamydia trachomatis 1

Weight-Based Dosing Considerations

Maximum Dose Caps

• Never exceed adult maximum doses regardless of weight-based calculation 1, 2
• For patients weighing ≥62 kg: cap at 500 mg day 1, then 250 mg daily for days 2-5 2

Weight-Specific Dosing (Alternative Approach)

• 15-25 kg: 200 mg once daily 1
• 26-35 kg: 300 mg once daily 1
• 36-45 kg: 400 mg once daily 1
• ≥46 kg: 500 mg once daily 1

Intravenous Administration

When IV Therapy is Required

• 10 mg/kg IV once daily (maximum 500 mg) on days 1-2, then transition to oral therapy as soon as clinically feasible 1
• Indicated for atypical pathogens when parenteral therapy is required 1
• Avoid prolonged IV therapy beyond 2 days when oral therapy is feasible 1
• Administration details: 1 mg/mL concentration over 3 hours OR 2 mg/mL concentration over 1 hour 1

Administration Guidelines

Timing and Food Interactions

• Can be taken with or without food 5
• Separate from aluminum- or magnesium-containing antacids by at least 2 hours, as they reduce absorption 1, 2, 3
• Oral suspension: administer 1 hour before or 2 hours after meals 1

Formulation Considerations

• Pediatric oral suspension is specifically designed to be reconstituted with water before administration 1
• Preferred formulation for children who cannot swallow tablets 1

Safety Monitoring and Adverse Effects

Common Adverse Effects

• Gastrointestinal disturbances (abdominal discomfort, diarrhea, nausea, vomiting) occur in approximately 5.3% of pediatric patients 1, 8
• Dizziness and headache 1
• Better gastrointestinal tolerance than erythromycin 1, 6
• Adverse events are mostly mild to moderate in severity 6, 8

Serious but Rare Adverse Effects

• Acute interstitial nephritis 1
• Allergic reactions/anaphylaxis 1
• Pseudomembranous colitis 1

Drug Interactions

• Monitor for QT interval prolongation when used with other QT-prolonging medications 1, 3
• Use caution with drugs metabolized by cytochrome P450 enzyme system 1, 3

Special Populations

Renal Impairment

• No dosage adjustment needed for GFR ≥10 mL/min 5
• Exercise caution in severe renal impairment (GFR <10 mL/min), as AUC increases 35% 5

Hepatic Impairment

• Use caution, as biliary excretion is the main route of elimination (approximately 6% appears unchanged in urine) 1
• No specific dosage adjustment recommendations available 5

Critical Clinical Pearls

Expected Clinical Response

• Children should demonstrate clinical improvement within 48-72 hours on adequate azithromycin therapy 1
• If no improvement or deterioration occurs, investigate for complications such as parapneumonic effusion 1

Resistance Concerns

• Azithromycin is associated with pneumococcal resistance and should be avoided in patients with significant risk of bacteremia 4
• Long half-life (68 hours) creates prolonged subinhibitory concentrations that may select for resistant organisms 3
• Consider alternative agents or combination therapy in areas with high rates of resistant S. pneumoniae 3

Common Pitfalls to Avoid

• Do not use azithromycin as first-line for typical bacterial pneumonia—amoxicillin remains preferred 2, 4
• Do not use standard 10 mg/kg dosing for strep throat—requires 12 mg/kg daily for 5 days 1
• Avoid prolonged IV therapy when oral transition is feasible 1
• Treatment discontinuation due to adverse events occurs in only 1.3% of pediatric patients 8

1, 2, 3, 5, 6, 8, 4, 7