Is a Z-pack (azithromycin) effective for treating otitis media?

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Last updated: June 25, 2025View editorial policy

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From the Guidelines

Azithromycin (Z-pack) is not recommended as a first-line treatment for otitis media. The preferred first-line antibiotics for otitis media are amoxicillin (80-90 mg/kg/day divided twice daily for 10 days in children or 500-875 mg twice daily for 5-7 days in adults) or amoxicillin-clavulanate if beta-lactamase producing bacteria are suspected, as recommended by the American Academy of Pediatrics and the American Academy of Family Physicians 1. Azithromycin should only be considered in patients with a true penicillin allergy, and even then, other alternatives like cefdinir or cefuroxime are often preferred.

Some key points to consider when treating otitis media include:

  • The most common bacterial causes of otitis media are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
  • Amoxicillin is generally effective against these pathogens when used in sufficient doses, and it is safe, inexpensive, and has an acceptable taste and narrow microbiologic spectrum 1.
  • The optimal duration of therapy for patients with otitis media is uncertain, but typical treatment courses range from 5-10 days.
  • Azithromycin does not provide adequate coverage against many strains of H. influenzae, which is a common pathogen in otitis media, and its use is associated with increasing resistance patterns to macrolide antibiotics 1.

If you have recurrent or persistent otitis media despite appropriate antibiotic therapy, you should consult with your healthcare provider for further evaluation and possibly referral to an ear, nose, and throat specialist.

From the FDA Drug Label

Protocol 2 In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin.

Protocol 4 In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days Each patient received active drug and placebo matched for the comparator. For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent.

Protocol 5 A double blind, controlled, randomized trial was performed at nine clinical centers Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Day 12 to 16) and Test of Cure (Day 28 to 32). For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator

Azithromycin (Z-pack) is effective for treating otitis media, with clinical success rates ranging from 70% to 89% in various studies 2. The most common side effects were diarrhea, vomiting, and rash.

  • Clinical success rates at Day 11 were 84% (Protocol 2) and 83% (Protocol 4) for azithromycin.
  • Clinical success rates at Day 30 were 70% (Protocol 2) and 74% (Protocol 4) for azithromycin.
  • A single dose of azithromycin (30 mg/kg) resulted in a clinical success rate of 87% at End of Therapy (Protocol 5) 2.

From the Research

Efficacy of Z-pack for Otitis Media

  • The efficacy of azithromycin (Z-pack) for treating otitis media has been evaluated in several studies 3, 4, 5, 6, 7.
  • A study published in 1996 found that azithromycin was comparable to amoxicillin/clavulanate in achieving clinical cure or improvement and presumed eradication of baseline pathogens in pediatric patients with acute otitis media 3.
  • Another study published in 2001 found that azithromycin was as effective as amoxicillin in preventing recurrent acute otitis media 4.
  • A study published in 2004 found that a single dose of azithromycin (30 mg/kg) was safe and effective for the treatment of uncomplicated acute otitis media in children 5.
  • A study published in 2006 found that the clinical efficiency of amoxicillin-clavulanate was equal to azithromycin in children with acute otitis media 6.
  • A review of four clinical trials published in 2005 found that single-dose azithromycin (30 mg/kg) had an end-of-treatment clinical success rate of 88% and a maintained clinical success rate at the end-of-study of 82% 7.

Comparison with Other Antibiotics

  • Azithromycin has been compared to amoxicillin/clavulanate in several studies, with mixed results 3, 6.
  • One study found that azithromycin was significantly better tolerated and had fewer relapses than amoxicillin/clavulanate 3.
  • Another study found that the clinical response rates were better in patients treated with amoxicillin-clavulanate, but this was not statistically significant 6.

Safety and Compliance

  • Azithromycin has been found to have a low incidence of adverse events, mostly mild and transitory gastrointestinal complaints 5, 7.
  • Compliance with azithromycin has been found to be excellent, particularly with single-dose regimens 5, 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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