What is azithromycin indicated for?

Azithromycin Indications

Azithromycin is FDA-approved for treating respiratory tract infections (community-acquired pneumonia, acute bacterial exacerbations of COPD, acute bacterial sinusitis), pharyngitis/tonsillitis, uncomplicated skin and skin structure infections, and sexually transmitted infections (urethritis/cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae, chancroid), as well as acute otitis media in pediatric patients. 1

FDA-Approved Indications in Adults

Respiratory Tract Infections

• Acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae 1
• Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Community-acquired pneumonia due to Chlamydophila pneumoniae, H. influenzae, Mycoplasma pneumoniae, or S. pneumoniae in patients appropriate for oral therapy 1
  • Critical caveat: Azithromycin should NOT be used in patients with pneumonia who have moderate to severe illness, cystic fibrosis, nosocomial infections, known/suspected bacteremia, require hospitalization, are elderly/debilitated, or have immunodeficiency/functional asplenia 1

Upper Respiratory Infections

• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in patients who cannot use first-line agents 1
  • Important limitation: Penicillin remains the drug of choice for S. pyogenes infection and rheumatic fever prophylaxis; azithromycin efficacy data for preventing rheumatic fever are not available 1

Skin and Soft Tissue Infections

• Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae 1
  • Note: Abscesses typically require surgical drainage 1

Sexually Transmitted Infections

• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 1
• Genital ulcer disease in men due to Haemophilus ducreyi (chancroid) 1
  • Critical warning: Efficacy in women has not been established due to small numbers in clinical trials 1
  • Syphilis consideration: Azithromycin at recommended doses should NOT be relied upon to treat syphilis; all patients with sexually-transmitted urethritis/cervicitis require serologic testing for syphilis 1

FDA-Approved Indications in Pediatric Patients

• Acute otitis media caused by H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae in patients appropriate for oral therapy 1
  • Same exclusions apply as in adults: not for use in patients with cystic fibrosis, nosocomial infections, bacteremia, requiring hospitalization, or with immunodeficiency/functional asplenia 1
• Pharyngitis/tonsillitis caused by S. pyogenes as an alternative to first-line therapy 1

Off-Label Uses Supported by Guidelines

Chronic Respiratory Conditions

• Long-term therapy in cystic fibrosis: For patients ≥6 years with persistent Pseudomonas aeruginosa in airway cultures, chronic azithromycin improves lung function and reduces exacerbations 2, 3
  • Dosing: 500mg three times weekly or 250mg daily 2, 3
• Bronchiectasis: For patients with ≥3 exacerbations in the previous 12 months 2, 3
  • Mandatory screening: Must screen for non-tuberculous mycobacteria (NTM) before initiating long-term therapy; current NTM infection is an absolute contraindication 2, 3, 4

Community-Acquired Pneumonia (Guideline-Based)

• Outpatient CAP without comorbidities: Azithromycin monotherapy is first-line for previously healthy patients 2, 3
• Outpatient CAP with comorbidities: Azithromycin combined with a β-lactam (high-dose amoxicillin, amoxicillin-clavulanate, ceftriaxone, cefpodoxime, or cefuroxime) 2, 3
• Hospitalized non-ICU CAP: Azithromycin plus β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) 2, 3
• ICU CAP: Azithromycin plus β-lactam for coverage of S. pneumoniae and Legionella species 2, 3

Sexually Transmitted Infections (Guideline-Based)

• Chlamydial urethritis: Doxycycline is preferred; azithromycin should only be used if doxycycline fails, is contraindicated, or adherence is a major concern 2, 4
  • Evidence note: Azithromycin efficacy for genital Mycoplasma genitalium has declined from 85.3% before 2009 to 67.0% since 2009 2

Special Populations

• Pregnancy: Azithromycin is the preferred macrolide when treatment is necessary, as it is safer than clarithromycin (which increases spontaneous abortion risk) 2, 3
• HIV-infected patients: Azithromycin is appropriate for bacterial respiratory infections 2, 3

Critical Contraindications and Warnings

Absolute Contraindications

• Hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide 2, 1
• History of cholestatic jaundice or hepatic dysfunction associated with previous azithromycin use 2, 1
• Current non-tuberculous mycobacteria (NTM) infection when considering long-term therapy 2, 3, 4

Cardiac Safety

• Fatal arrhythmias: Azithromycin can cause QT prolongation, ventricular tachycardia, and torsades de pointes 2, 4
• Avoid or use with extreme caution in patients with known QT prolongation or history of torsades de pointes 4

Resistance Considerations

• High macrolide resistance areas: Do NOT use azithromycin monotherapy in regions with >25% macrolide-resistant S. pneumoniae 2, 3, 4
• Tuberculosis risk: Empiric azithromycin for pneumonia may delay tuberculosis diagnosis; consider TB screening in high-risk populations before initiating therapy 4

Drug Interactions

• Avoid concurrent use with terfenadine, astemizole, pimozide, or cisapride 2
• Multiple interactions possible with antiarrhythmics, oral anticoagulants, azole antifungals, benzodiazepines, calcium-channel blockers, carbamazepine, and others 2

Common Pitfalls to Avoid

• Using monotherapy for severe pneumonia: Combination therapy is mandatory for hospitalized patients to prevent treatment failure 2, 3, 4
• Ignoring local resistance patterns: Prescribing azithromycin monotherapy without considering local resistance can lead to treatment failure 2, 3, 4
• Failing to screen for NTM: Not screening before long-term macrolide therapy can lead to unnecessary treatment and harm 2, 3, 4
• Relying on azithromycin for syphilis: It cannot be used to treat or exclude syphilis in patients with sexually transmitted infections 1
• Using in inappropriate pneumonia patients: Avoid in patients with risk factors requiring hospitalization or parenteral therapy 1