What are the indications for Azithromycin (macrolide antibiotic)?

Azithromycin Indications

Azithromycin is FDA-approved for treating mild to moderate infections caused by susceptible organisms including respiratory tract infections, skin/soft tissue infections, and sexually transmitted infections, but should not be used for pneumonia requiring hospitalization or in patients with significant risk factors. 1

FDA-Approved Indications

Respiratory Tract Infections

• Acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
• Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae
• Community-acquired pneumonia (CAP) due to Chlamydophila pneumoniae, H. influenzae, Mycoplasma pneumoniae, or S. pneumoniae in patients appropriate for oral therapy
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy when first-line therapy cannot be used

Skin and Soft Tissue Infections

• Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae
  • Note: Abscesses usually require surgical drainage

Sexually Transmitted Infections

• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae
• Genital ulcer disease in men due to Haemophilus ducreyi (chancroid)

Important Off-Label Uses

Pertussis (Whooping Cough)

• Preferred treatment for pertussis in infants <1 month of age 2
• Treatment regimen for older infants and children:
  • <6 months: 10 mg/kg per day for 5 days

  • 6 months: 10 mg/kg (maximum: 500 mg) on day 1, followed by 5 mg/kg per day (maximum: 250 mg) on days 2-5

  • Adults: 500 mg on day 1, followed by 250 mg per day on days 2-5

Mycobacterium avium complex (MAC)

• Secondary prophylaxis (chronic maintenance therapy) for disseminated MAC infection in HIV-infected patients 2
• Used in combination with ethambutol with or without rifabutin
• Preferred over clarithromycin during pregnancy due to safety profile

Bacterial Respiratory Infections in HIV

• Prophylaxis for recurrent serious bacterial respiratory infections in HIV-infected patients 2

Acne Vulgaris

• Not FDA-approved for acne treatment (off-label use) 2
• Contraindicated in patients with hypersensitivity to azithromycin, erythromycin, macrolides, or ketolides, and in those with history of cholestatic jaundice/hepatic dysfunction associated with previous azithromycin use

Dosing Considerations

Standard Adult Dosing

• Respiratory infections: 500 mg on day 1, followed by 250 mg once daily for 4 days
• Sexually transmitted infections: Single 1g dose for chlamydia 3

Pediatric Dosing

• Generally 10 mg/kg on day 1 (maximum 500 mg), followed by 5 mg/kg (maximum 250 mg) on days 2-5 4
• For pertussis in infants <6 months: 10 mg/kg per day for 5 days 2

Pharmacodynamic Properties

• Azithromycin is a time-dependent antibiotic with moderate to prolonged persistent effect 2
• Unlike traditional time-dependent antibiotics where time above MIC is the key parameter, for azithromycin the AUC to MIC ratio correlates with efficacy 2
• The AUC to MIC ratio that yields maximal efficacy is approximately 25 2

Contraindications and Precautions

Contraindications

• Hypersensitivity to azithromycin, erythromycin, any macrolide, or any ketolide
• History of cholestatic jaundice/hepatic dysfunction associated with previous azithromycin use
• QTc prolongation (>450 ms for men and >470 ms for women) 2

Adverse Effects

• Cardiovascular: palpitations, chest pain, arrhythmias, QT prolongation, torsade de pointes
• Gastrointestinal: dyspepsia, flatulence, diarrhea, loose stools, nausea, vomiting, abdominal pain
• Hepatic: cholestatic jaundice, hepatic dysfunction
• Skin reactions: pruritus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Antimicrobial Resistance Concerns

• Long half-life (68 hours) creates a prolonged period of subinhibitory concentrations, potentially increasing risk of resistance development 2
• Studies have shown significant increases in azithromycin-resistant S. pneumoniae after treatment, with resistance rates rising from 2% before treatment to 55% 2-3 weeks after treatment 2
• For this reason, azithromycin should be used judiciously and only when clearly indicated

Monitoring

• ECG should be performed prior to initiation to assess QTc interval 2
• Baseline liver function tests should be measured 2
• Follow-up ECG and liver function tests should be checked 1 month after starting treatment 2

Azithromycin's unique pharmacokinetic profile with extensive tissue distribution and intracellular accumulation makes it particularly effective against intracellular pathogens, despite relatively low serum concentrations 5, 6. This allows for convenient once-daily dosing and shorter treatment courses compared to many other antibiotics.