What is the comparison between Azithromycin and Amoxicillin for the treatment of streptococcal pharyngitis?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 19, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Amoxicillin is generally recommended as the first-line antibiotic for the treatment of streptococcal pharyngitis due to its narrower spectrum of activity and lower risk of contributing to antibiotic resistance. Azithromycin may be considered for patients who are allergic to penicillin or have other specific contraindications to amoxicillin 1.

Key Differences Between Azithromycin and Amoxicillin

  • The typical dose of amoxicillin for strep throat is 500 mg orally three times a day for 10 days, while azithromycin is typically given as 500 mg orally on the first day, followed by 250 mg orally once daily for the next 4 days 1.
  • Amoxicillin has a narrower spectrum of activity and is less likely to contribute to antibiotic resistance compared to azithromycin 1.
  • Azithromycin may be more convenient for patients due to its shorter treatment duration, but it is also more expensive and has a broader spectrum of activity, which may increase the risk of antibiotic resistance 1.

Important Considerations

  • It's essential to complete the full course of antibiotics as prescribed to ensure effective treatment and prevent potential complications 1.
  • Patients with penicillin allergy may be considered for alternative antibiotics such as cephalexin, cefadroxil, clindamycin, or azithromycin 1.
  • The choice of antibiotic should be based on the patient's specific needs and medical history, as well as the potential risks and benefits of each antibiotic 1.

From the FDA Drug Label

In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S. pyogenes) Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS): Three U. S. Streptococcal Pharyngitis Studies Azithromycin vs. Penicillin V EFFICACY RESULTS Day 14Day 30 Bacteriologic Eradication: Azithromycin323/340 (95%)255/330 (77%) Penicillin V242/332 (73%)206/325 (63%) Clinical Success (Cure plus improvement): Azithromycin336/343 (98%)310/330 (94%) Penicillin V284/338 (84%)241/325 (74%)

The comparison between Azithromycin and Amoxicillin for the treatment of streptococcal pharyngitis is not directly provided in the given text, as the text compares Azithromycin to Penicillin V. However, it can be noted that Azithromycin was compared to Amoxicillin/Clavulanate in the treatment of acute bacterial sinusitis, but not specifically for streptococcal pharyngitis. Therefore, based on the provided information, no direct comparison can be made between Azithromycin and Amoxicillin for the treatment of streptococcal pharyngitis 2.

From the Research

Comparison of Azithromycin and Amoxicillin

  • The comparison between Azithromycin and Amoxicillin for the treatment of streptococcal pharyngitis is based on limited evidence from one unpublished trial in children, as reported in 3, 4, 5.
  • This trial found that azithromycin in a single dose may have a better cure rate compared to amoxicillin for 10 days, with an odds ratio (OR) of 0.29 (95% CI 0.11 to 0.73) in the per-protocol analysis, but not in the intention-to-treat analysis (OR 0.76,95% CI 0.55 to 1.05) 3, 4, 5.
  • However, children experienced more adverse events with azithromycin compared to amoxicillin (OR 2.67,95% CI 1.78 to 3.99) 3, 4, 5.
  • The evidence is considered very low-certainty due to the limited number of trials and the poor reporting of randomisation, allocation concealment, and blinding 3, 4, 5.

Effectiveness of Amoxicillin

  • Amoxicillin is considered equally effective as penicillin for the treatment of streptococcal pharyngitis, and is more palatable 6.
  • A meta-analysis found that once-daily amoxicillin is not inferior to other dosages of amoxicillin or penicillin V for the treatment of streptococcal tonsillitis 7.
  • The results of this meta-analysis showed no statistically significant differences in terms of negative throat culture, persistence of the same serotype, clinical failure, or adverse effects between once-daily amoxicillin and other dosages of amoxicillin or penicillin V 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2016

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2021

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2023

Research

Diagnosis and treatment of streptococcal pharyngitis.

American family physician, 2009

Research

[Treatment of streptococcal tonsillitis with once-a-day amoxicillin: a meta-analysis].

Anales de pediatria (Barcelona, Spain : 2003), 2011

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.