What infections are treated with azithromycin?

Azithromycin Indications

Azithromycin is primarily indicated for treating bacterial respiratory tract infections, sexually transmitted infections (especially chlamydia and gonorrhea), and skin/soft tissue infections caused by susceptible organisms. 1

FDA-Approved Indications

Respiratory Tract Infections

• Community-acquired pneumonia caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in patients appropriate for oral therapy 1
• Acute bacterial exacerbations of COPD due to H. influenzae, Moraxella catarrhalis, or S. pneumoniae 1
• Acute bacterial sinusitis caused by H. influenzae, M. catarrhalis, or S. pneumoniae 1
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative when first-line therapy cannot be used 1

Sexually Transmitted Infections

• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae 1
• Genital ulcer disease in men caused by Haemophilus ducreyi (chancroid) 1

Critical caveat: The FDA label explicitly states azithromycin should NOT be relied upon to treat syphilis at recommended doses, and all patients with sexually transmitted urethritis/cervicitis require serologic testing for syphilis 1

Skin and Soft Tissue Infections

• Uncomplicated skin and skin structure infections caused by Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae 1

Current Guideline-Based Position on Chlamydia Treatment

Azithromycin as Second-Line for Chlamydia

The most recent WHO guidelines (2024) recommend azithromycin ONLY as an alternative option for chlamydial urethritis, to be used when doxycycline has failed, is contraindicated, or when there are major adherence concerns with the 7-day doxycycline regimen. 2

This represents a significant shift from historical practice because:

• Declining efficacy: Azithromycin efficacy for genital chlamydia was 97% but failed to establish non-inferiority to doxycycline (100% efficacy) 2
• FDA safety warnings: The FDA has issued warnings about azithromycin safety that influenced this guideline change 2
• Mycoplasma resistance: Microbial cure rates for Mycoplasma genitalium with azithromycin fell from 85.3% before 2009 to 67.0% since 2009 2

When Azithromycin Remains Preferred for Chlamydia

• Pregnancy: Azithromycin 1 g single dose is the preferred treatment during pregnancy (doxycycline is contraindicated) 3, 4
• Compliance concerns: Single-dose therapy enables directly observed treatment in populations with erratic healthcare-seeking behavior 3, 4
• Pediatric patients ≥8 years weighing >45 kg: Azithromycin 1 g single dose is an acceptable option 3, 4

Spectrum of Activity

Enhanced Activity Compared to Erythromycin

• Gram-negative coverage: Superior activity against H. influenzae and M. catarrhalis 5, 6
• Atypical pathogens: Excellent activity against Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Chlamydia trachomatis 5, 7, 6
• Sexually transmitted organisms: Effective against N. gonorrhoeae, Ureaplasma urealyticum, and Borrelia burgdorferi 6

Resistance Considerations

Organisms resistant to erythromycin are also resistant to azithromycin, and susceptibility testing should be performed when treating S. pyogenes infections because some strains are resistant. 1

Pharmacokinetic Advantages Enabling Short-Course Therapy

• Tissue selectivity: Azithromycin achieves tissue concentrations far exceeding serum levels, with concentrations in respiratory tract, gynecological tissue, and prostate remaining above MIC for several days 5, 8
• Extended half-life: Terminal elimination half-life exceeds 60 hours, allowing once-daily dosing for 3-5 days to match efficacy of comparators given for 7-10 days 5, 8, 6
• Intracellular penetration: Rapidly penetrates phagocytic cells with release at local infection sites 5

Common Pitfalls to Avoid

• Do not use for moderate-to-severe pneumonia: Azithromycin should not be used in patients with pneumonia requiring hospitalization, those with cystic fibrosis, nosocomially acquired infections, known/suspected bacteremia, or immunodeficiency 1
• Do not assume syphilis coverage: High-dose short-course regimens for non-gonococcal urethritis may mask incubating syphilis symptoms 1
• Do not use as first-line for chlamydia in non-pregnant adults: Current guidelines prioritize doxycycline due to superior efficacy and safety concerns with azithromycin 2
• Verify gonorrhea co-treatment: When treating gonorrhea, always provide concurrent chlamydia coverage, but recognize that azithromycin alone is insufficient for gonorrhea in many regions due to resistance 3