Azithromycin (Zithromax®) versus Amoxicillin

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Main differences between Azithromycin and Amoxicillin

Azithromycin Amoxicillin
Brand names
• Zithromax®
• Z-pak®
• Amoxil®
Drug class
Macrolide antibiotic,
Penicillin antibiotic,
Spectrum of activity
Excellent activity against atypical pathogens No activity against atypical pathogens
40 hours 1 hour
Oral bioavailability
~40% 74-92%
Side effects
  • High rate of diarrhea and rash
Special populations
• Alternative antibiotic for patients with penicillin allergy

• Good choice for patients with questionable compliance
• Contraindicated in patients with penicillin allergy
Pregnancy category


Chronic obstructive pulmonary disease

Azithromycin and amoxicillin have similar efficacy and tolerability in the treatment of acute exacerbation of chronic obstructive pulmonary disease 6. Both antibiotics improve symptoms such as cough and shortness of breath.

Results of randomized comparison between azithromycin and amoxicillin for infectious exacerbation of chronic obstructive pulmonary disease6 Azithromycin Amoxicillin
Regimen 500 mg/day for 3 days 500 mg every 8 hours for 10 days
Cure or improvement on Day 10 85% 78%
Cure or improvement at One month 83% 78%


Both amoxicillin and azithromycin are effective in the treatment of cervical Chlamydia trachomatis infection during pregnancy. However, azithromycin seems to have a lower rate of recurrent infection2. Amoxicillin is slightly better tolerated1.

Results of randomized single-blind trial of women diagnosed with C. trachomatis2 Azithromycin Amoxicillin
Regimen single 1 g dose 500 mg 3 times daily for 7 days
Number of patients tested positive at follow-up test of cure 1 of 19 (5%) 3 of 15 (20%)
Moderate to severe gastrointestinal side effects 40% 17%

Results of randomized controlled trial of pregnant women with C. trachomatis11 Azithromycin Amoxicillin
Regimen single 1 g dose 500 mg 3 times daily for 7 days
Treatment efficacy rate 64% 58%
Number of women intolerant to study drug 6 (10.9%) 3 (5.5%)

Ear infection (Otitis media)

Azithromycin is as effective as amoxicillin for the treatment of children with otitis media3. Diarrhea occurs more frequently with amoxicillin.

Results of double blind, double dummy, multinational, clinical trial of children (6-30 months of age) with AOM 3 Azithromycin Amoxicillin
Regimen single 30 mg/kg dose 90 mg/kg in 2 divided doses for 10 days
Clinical success rates 84% 84%
Clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects 80% 83%
Side effects rate



Compliance 100% 90%

Results of a double blind, randomised controlled trial of Aboriginal children with AOM5 Azithromycin Amoxicillin
Regimen single 30 mg/kg dose 50 mg/kg in 2 divided doses for a min. of 7 days
Clinical failure rate 50% (82 of 165) 54% (83 of 155)
Proportion of children after the treatment with nasal carriage of
Streptococcus pneumoniae

Haemophilus influenzae


Nasal carriage of S. pneumoniae with intermediate or full resistance to penicillin 10% 16%
Carriage of azithromycin-resistant S. pneumoniae 10% 3%

Lyme disease

Amoxicillin is better than azithromycin for erythema migrans4.

Results of randomized, double-blind, double-dummy, multicenter study - treatment of erythema migrans skin lesions4 Azithromycin Amoxicillin
Regimen 500 mg once daily for 7 days 500 mg three times daily for 20 days
Complete resolution of disease at day 20 rate 88% 76%
Relapse rate 16% 4%


Further reading


  • 1. Jacobson GF, Autry AM, Kirby RS, Liverman EM, Motley RU. Am J Obstet Gynecol. 2001 Jun;184(7):1352-4; discussion 1354-6. PubMed
  • 2. Kacmar J, Cheh E, Montagno A, Peipert JF. A randomized trial of azithromycin versus amoxicillin for the treatment of Chlamydia trachomatis in pregnancy. Infect Dis Obstet Gynecol. 2001;9(4):197-202. PubMed
  • 3. Arguedas A, Emparanza P, Schwartz RH, Soley C, Guevara S, de Caprariis PJ, Espinoza G. Pediatr Infect Dis J. 2005 Feb;24(2):153-61. PubMed
  • 4. Luft BJ, Dattwyler RJ, Johnson RC, Luger SW, Bosler EM, Rahn DW, Masters EJ, Grunwaldt E, Gadgil SD. Azithromycin compared with amoxicillin in the treatment of erythema migrans. Ann Intern Med. 1996 May 1;124(9):785-91.
  • 5. Morris PS, Gadil G, McCallum GB, Wilson CA, Smith-Vaughan HC, Torzillo P, Leach AJ. Single-dose azithromycin versus seven days of amoxycillin in the treatment of acute otitis media in Aboriginal children (AATAAC): a double blind, randomised controlled trial. Med J Aust. 2010 Jan 4;192(1):24-9. PubMed
  • 6. Andre-Alves MR, Jardim JR, Frare e Silva R, Fiss E, Freire DN, Teixeira PJ. Comparison between azithromycin and amoxicillin in the treatment of infectious exacerbation of chronic obstructive pulmonary disease. J Bras Pneumol. 2007 Jan-Feb;33(1):43-50. PubMed

Published: January 12, 2014
Last updated: January 23, 2018


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