Would azithromycin (azithro) and Augmentin (amoxicillin/clavulanate) be an appropriate combination for treatment?

Azithromycin and Augmentin Combination Therapy: Redundant and Not Recommended

The combination of azithromycin and Augmentin (amoxicillin/clavulanate) is generally redundant and not recommended for most infections, as they have overlapping coverage and increased risk of adverse effects without significant clinical benefit. 1

Rationale Against Combined Use

Overlapping Antimicrobial Coverage

• Augmentin (amoxicillin/clavulanate) provides excellent coverage against many common respiratory and skin pathogens including:

  • Streptococcus pneumoniae
  • Haemophilus influenzae (including beta-lactamase producers)
  • Moraxella catarrhalis
  • Many Gram-positive organisms 1, 2

• Azithromycin covers:

  • Many of the same pathogens as Augmentin
  • Atypical pathogens (Mycoplasma, Chlamydia)
  • Some Gram-negative organisms 3

Increased Risk of Adverse Effects

• Combining these antibiotics increases the risk of side effects without proportional clinical benefit:
  • Augmentin commonly causes diarrhea (reported in up to 14.6% of patients) 3
  • Azithromycin can cause gastrointestinal effects and has FDA warnings about safety 1
  • Studies show higher adverse event rates with Augmentin (21.3%) compared to azithromycin alone (14%) 4

Specific Clinical Scenarios

Respiratory Infections

• For community-acquired pneumonia, the IDSA/ATS guidelines recommend either a beta-lactam (like Augmentin) OR a macrolide (like azithromycin), not both, except in specific severe cases 1
• For acute exacerbations of chronic bronchitis, comparative studies show either agent alone is effective, with no benefit to combination therapy 5, 4

Skin and Soft Tissue Infections

• Guidelines recommend amoxicillin-clavulanic acid, dicloxacillin, cefuroxime, or cefalexin as appropriate monotherapy for mild skin infections 1
• No recommendation exists for adding azithromycin to these regimens

ENT Infections

• For otitis media, sinusitis, and pharyngitis, either agent alone has shown efficacy
• Head-to-head studies show comparable or better outcomes with Augmentin compared to azithromycin for bacterial otitis media 6

Exceptions Where Combination Might Be Considered

1. Suspected or confirmed co-infection with typical and atypical pathogens

   • In severe community-acquired pneumonia where both typical bacterial and atypical coverage is needed 1

2. Treatment failure with monotherapy

   • When a patient has failed initial therapy with either agent alone and broader coverage is needed 2

3. Specific polymicrobial infections

   • Where documented pathogens require different antimicrobial mechanisms

Conclusion

For most common infections, using either Augmentin OR azithromycin as monotherapy (based on the suspected pathogens) is more appropriate than combining them. This approach minimizes adverse effects, reduces antibiotic resistance pressure, and follows antimicrobial stewardship principles while maintaining clinical efficacy.

If broader coverage is needed, consider alternative single agents or different combinations based on suspected pathogens and local resistance patterns.