What is azithromycin used for?

Azithromycin Clinical Indications

Azithromycin is a macrolide antibiotic used primarily for community-acquired respiratory tract infections, sexually transmitted infections, and as chronic therapy in cystic fibrosis patients with Pseudomonas aeruginosa colonization. 1, 2

FDA-Approved Indications

The FDA has approved azithromycin for the following bacterial infections in adults 2:

• Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy 2
• Acute bacterial exacerbations of COPD due to H. influenzae, Moraxella catarrhalis, or S. pneumoniae 2
• Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae 2
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy 2
• Uncomplicated skin and skin structure infections due to Staphylococcus aureus, S. pyogenes, or Streptococcus agalactiae 2
• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 2
• Genital ulcer disease in men due to Haemophilus ducreyi (chancroid) 2

Community-Acquired Pneumonia Treatment Algorithms

Outpatient CAP (Previously Healthy, No Comorbidities)

Azithromycin monotherapy is first-line treatment for previously healthy outpatient CAP patients without comorbidities 1. This recommendation is based on high cure rates in prospective randomized trials and excellent coverage of typical and atypical pathogens 3.

Outpatient CAP (With Comorbidities)

Azithromycin combined with a β-lactam (high-dose amoxicillin, amoxicillin-clavulanate, ceftriaxone, cefpodoxime, or cefuroxime) is recommended for outpatients with comorbidities 1. This combination provides broader coverage against drug-resistant S. pneumoniae 3.

Hospitalized Non-ICU CAP

Azithromycin plus a β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) is recommended for hospitalized non-ICU patients 3, 1. Multiple retrospective studies demonstrate significant mortality reduction with this combination compared to cephalosporin monotherapy 3.

ICU-Admitted CAP

Azithromycin plus a β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) is the minimal recommended treatment for ICU patients 3, 1. This provides coverage for S. pneumoniae and Legionella species, which are critical in severe pneumonia 3.

Pediatric Respiratory Infections

Azithromycin is effective in children for 3, 4:

• Pneumonia in children ≥5 years: Macrolides like azithromycin may be used as first-line empirical treatment since Mycoplasma pneumoniae is more prevalent in older children 3
• Suspected mycoplasma or chlamydia pneumonia: Macrolide antibiotics should be used regardless of age 3
• Otitis media: Azithromycin (3-day course of 10 mg/kg/day or 5-day course with 10 mg/kg on day 1, then 5 mg/kg/day) is as effective as amoxicillin/clavulanic acid, clarithromycin, or cefaclor 4
• Streptococcal pharyngitis/tonsillitis: Azithromycin at 12 mg/kg/day for 5 days is as effective as penicillin V, though more recurrences occur with standard dosing 4

Chronic Therapy in Cystic Fibrosis

Long-term azithromycin therapy is strongly recommended for patients ≥6 years with persistent Pseudomonas aeruginosa in airway cultures 3, 1. The evidence supporting this is robust:

• Improves lung function: Absolute FEV1 improvement of 3.6-6.2% in three randomized controlled trials 3
• Reduces exacerbations: Four of five trials showed decreased pulmonary exacerbations, with one large trial (n=263) demonstrating a 50% reduction in exacerbations even without P. aeruginosa infection 3
• Dosing: 500mg three times weekly or 250mg daily 1

Critical Safety Requirement for CF Patients

Screen for nontuberculous mycobacteria (NTM) before initiating azithromycin and reassess every 6-12 months 3, 1. Chronic azithromycin monotherapy in patients with occult or active NTM infection can lead to resistance and complicate NTM treatment 3. Current NTM infection is an absolute contraindication 1.

Sexually Transmitted Infections

Chlamydial Urethritis/Cervicitis

Doxycycline is now preferred over azithromycin for chlamydial urethritis, with azithromycin reserved only if doxycycline fails, is contraindicated, or adherence is a major concern 1. This represents a shift from previous practice due to emerging resistance patterns.

Mycoplasma genitalium

Azithromycin efficacy for M. genitalium has significantly declined from 85.3% before 2009 to 67.0% since 2009 1. Alternative therapies should be considered for this pathogen.

Pregnancy

Azithromycin is the preferred macrolide during pregnancy, as it is safer than clarithromycin 1.

Important Contraindications and Warnings

Absolute Contraindications 1, 2

• Hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide
• Current nontuberculous mycobacteria (NTM) infection (for chronic therapy)

Cardiac Warnings

Azithromycin can cause QT prolongation, ventricular tachycardia, and torsades de pointes 1. The risk is small (1.1 cases per 1000 person-years) but requires careful patient evaluation 5. Avoid or use with extreme caution in patients with:

• Known QT prolongation
• History of torsades de pointes
• Concurrent use with terfenadine, astemizole, pimozide, or cisapride 1

Resistance Considerations

Do not use azithromycin monotherapy in regions with >25% macrolide-resistant S. pneumoniae 1. In such areas, combination therapy with a β-lactam is mandatory.

Tuberculosis Screening

Consider TB screening in high-risk populations before initiating empiric azithromycin therapy for pneumonia to avoid delayed tuberculosis diagnosis 1.

Inappropriate Use in Pneumonia

Azithromycin should NOT be used in patients with pneumonia who have 2:

• Moderate to severe illness requiring hospitalization
• Cystic fibrosis
• Nosocomially acquired infections
• Known or suspected bacteremia
• Elderly or debilitated status
• Immunodeficiency or functional asplenia

These patients require parenteral therapy or broader-spectrum coverage 2.

Common Adverse Effects

The most common adverse events are gastrointestinal 5, 4:

• Nausea, diarrhea, dispepsia, and colitis (occurring in <5% of patients) 5
• Generally mild to moderate in severity 4
• Better gastrointestinal tolerance than erythromycin 4

Long-term use may cause 5:

• Decreased hearing
• Colonization with azithromycin-resistant organisms

Pharmacokinetic Advantages

Azithromycin offers several practical advantages 6, 7:

• Once-daily dosing due to long terminal half-life (up to 5 days) 6
• Short treatment courses (3-5 days for most infections) 6
• Extensive tissue distribution with tissue concentrations exceeding those of erythromycin 6
• Few drug interactions compared to other macrolides 7
• Acid stable allowing reliable oral absorption 6