Azithromycin (Zithromax®) versus Doxycycline

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

Difference between Azithromycin and Doxycycline

  Azithromycin Doxycycline
Drug class Macrolide antibiotic Tetracycline antibiotic
Mechanism of action Inhibits bacterial protein synthesis -- bind to the 50s ribosomal subunits, inhibiting peptidyl transfer. Inhibits bacterial protein synthesis -- bind to the 30S ribosomal subunits, block the A site on the ribosome, preventing the binding of aminoacyl tRNAs.
Excretion Biliary,
mainly as unchanged drug in the faeces
urinary excretion about 6%
excreted in the urine (40%) and feces
not metabolized in the liver
Half-life 40 hours 18 hours
Spectrum of activity   Effective for many unusual diseases
  Poor activity against Group A streptococci
Side effects Excellent safety and tolerability Photosensitivity reactions
Damages developing teeth and binds to bone
Irritation of oesophagus
Special populations Pregnancy category B
Approved for infants >3 months and children
Pregnancy category D
Should be avoided during tooth development (children <8 years)
Should not be used in severe hepatic or renal disease
Drug interactions No clinically significant drug interactions Decreased absorption with antacids, iron, and zinc.
Can enhance the anticoagulant effect of warfarin.
Food Tablets and suspension are not affected by food12. Food impairs absorption of azithromycin capsules. Dairy products reduce peak plasma concentrations by 20%


Azithromycin vs Doxycycline for Chlamydia

Both antibiotics are recommended as first-line regimens first-line regimens for chlamydia infection.

In clinical trials2, 11, the bacteriological cure rate of a single dose of azithromycin 1000 mg (95 to 100%) was similar to that of doxycycline 200 mg/day for 7 days (88 to 100%).

However, according to the recent research1 azithromycin may be particularly effective against persistent chlamydia. In contrast, doxycycline may not be as effective in treating persistent infection.

Chronic chlamydial infections (e.g. pelvic inflammatory disease, trachoma) are a mixture of acute and persistent infections. Therefore azithromycin would be more effective for the treatment of chlamydial infections than doxycycline1.

Results of randomized trial comparing azithromycin with doxycycline for the treatment of urogenital chlamydia11 Azithromycin Doxycycline
Regimen single 1 g dose 100 mg twice daily for 7 days
Treatment failures 3.2%
(5 participants of 284)
(0 participants of 283)
Efficacy rate 97% 100%

Results of meta-analysis of randomized clinical trials evaluating azithromycin versus doxycycline for genital chlamydia2 Azithromycin Doxycycline
Regimen single 1 g dose 100 mg twice daily for 7 days
Cure rates 97% 98%
Adverse events 25% 23%

According to the 2014 meta-analysis10 of randomized controlled trials comparing azithromycin with doxycycline for the treatment of genital chlamydia there may be an increased efficacy of up to 3% for doxycycline compared with azithromycin for urogenital chlamydia and about 7% increased efficacy for doxycycline for symptomatic urethral infection in men.

Chlamydial conjunctivitis

Azithromycin is as effective as standard doxycycline in the treatment of adult inclusion conjunctivitis 8.

Results of open, randomized clinical trial of azithromycin vs doxycycline in the treatment of inclusion conjunctivitis8 Azithromycin Doxycycline
Regimen single 1 g dose 100 mg twice daily for 10 days
Eradication of C. trachomatis, number of patients (%) 23 of 25 (92%) 25 of 26 (96%)
Clinical cure, number of patients (%) 15 (60%) 18 (69%)


Both azithromycin and doxycycline are effective in the treatment of non-gonococcal mucopurulent endocervicitis3.

Results of prospective randomised study of azithromycin versus doxycycline in the treatment of non-gonococcal mucopurulent endocervicitis 3 Azithromycin Doxycycline
Regimen single 1 g dose 100 mg twice daily for 7 days
Eradication rate 71.4% 77.3%


Azithromycin (500 mg once a day for 4 days per month) appears to be as effective as daily doxycycline (100 mg daily)4. However, in patients older than 18 years doxycycline is more effective.

According to the 2018 research work, pulsed azithromycin (500 mg 1-3 times weekly) provides equivalent efficacy to daily doxycycline in the treatment of moderate or severe acne14.

Lyme disease (Erythema migrans)

Azithromycin is equally effective as doxycycline in the treatment of Lyme disease5.

Results of randomized, multicenter, open comparison of azithromycin and doxycycline in the treatment of erythema migrans5 Azithromycin Doxycycline
Regimen 500 mg twice on the 1st day, followed by 500 mg once daily for the next 4 days 100 mg twice daily for 14 days
Clinical success, number of patients (%) 46 (95.8%) 33 (82.5%)
Minor symptoms persisted or appeared in the posttreatment period in 2 of 47 patients in 3 of 35 patients
Major manifestations appeared no in 2 patients

According to the 2014 animal study6, a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. However, 4% preparation of doxycycline cream provided no protection.


Doxycycline is traditionally prescribed in ocular conditions, including blepharitis. Azithromycin is used to treat blepharitis as an effective alternative to doxycycline.

Azithromycin dosage for blepharitis: 250-500 mg 1-3 times a week, or 1 g per week, for 3 weeks.

Doxycycline dosage for blepharitis: 100 mg twice daily for 1 month.


Meibomian gland dysfunction (MGD)

Both doxycycline and azithromycin improve symptoms of meibomian gland dysfunction13, including dryness, redness and swelling of the eyelids, and ocular surface staining. However, azithromycin is more effective and allows for much shorter treatment regimen.

Azithromycin dosage for MGD: 500 mg on day 1 and then 250 mg per day for 4 days.

Doxycycline dosage for MGD: 200 mg per day for 1 month.

Mycoplasma genitalium infection

Azithromycin is more effective than doxycycline for the treatment of Mycoplasma genitalium -associated urethritis in men7.

Results of randomized comparison of azithromycin and doxycycline for Mycoplasma genitalium-positive urethritis in men7 Azithromycin Doxycycline
Regimen single 1 g dose 100 mg twice daily for 7 days
Number (%) of patients positive for M. genitalium at the early initial follow-up visit 3 (13%) of 23 17 (55%) of 31

Pelvic inflammatory disease

Azithromycin plus ceftriaxone is superior to doxycycline plus ceftriaxone in the treatment of mild pelvic inflammatory disease 9.

Results of randomized, double-blind, controlled study of azithromycin plus ceftriaxone in the treatment of mild, uncomplicated PID compared to doxycycline plus ceftriaxone 9 Azithromycin Doxycycline
Regimen 250 mg of ceftriaxone intramuscularly plus 1 g of azithromycin weekly for 2 weeks 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline twice daily for 2 weeks
Clinical cure rates 90.3% (56 of 62 patients) 72.4% (42 of 58 patients)

Further reading


  • 1. Reveneau N, Crane DD, Fischer E, Caldwell HD. Antimicrob Agents Chemother. 2005 May;49(5):1787-93.
  • 2. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis. 2002 Sep;29(9):497-502. PubMed
  • 3. Sendag F, Terek C, Tuncay G, Ozkinay E, Guven M. Single dose oral azithromycin versus seven day doxycycline in the treatment of non-gonococcal mucopurulent endocervicitis. Aust N Z J Obstet Gynaecol. 2000 Feb;40(1):44-7. PubMed
  • 4. Babaeinejad S, Khodaeiani E, Fouladi RF. Comparison of therapeutic effects of oral doxycycline and azithromycin in patients with moderate acne vulgaris: What is the role of age? J Dermatolog Treat. 2011 PubMed
  • 5. Barsic B, Maretic T, Majerus L, Strugar J. Comparison of azithromycin and doxycycline in the treatment of erythema migrans. Infection. 2000 May-Jun;28(3):153-6. PubMed
  • 6. Piesman J, Hojgaard A, Ullmann AJ, Dolan MC. Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model. Antimicrob Agents Chemother. 2014 Jan;58(1):348-51. PubMed
  • 7. Mena LA, Mroczkowski TF, Nsuami M, Martin DH. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin Infect Dis. 2009 Jun 15;48(12):1649-54. PubMed
  • 8. Katusic D, Petricek I, Mandic Z, Petric I, Salopek-Rabatic J, Kruzic V, Oreskovic K, Sikic J, Petricek G. Azithromycin vs doxycycline in the treatment of inclusion conjunctivitis. Am J Ophthalmol. 2003 Apr;135(4):447-51. PubMed
  • 9. Savaris RF, Teixeira LM, Torres TG, Edelweiss MI, Moncada J, Schachter J. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol 2007;110:53–60. PubMed
  • 10. Kong FY, Tabrizi SN, Law M, Vodstrcil LA, Chen M, Fairley CK, Guy R, Bradshaw C, Hocking JS. Azithromycin Versus Doxycycline for the Treatment of Genital Chlamydia Infection: A Meta-analysis of Randomized Controlled Trials. Clin Infect Dis. 2014 Apr 11 PubMed
  • 11. Geisler WM, Uniyal A, Lee JY, Lensing SY, Johnson S, Perry RC, Kadrnka CM, Kerndt PR. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection. N Engl J Med. 2015 Dec 24;373(26):2512-21. NEJM
  • 12. Foulds G1, Luke DR, Teng R, et al. The absence of an effect of food on the bioavailability of azithromycin administered as tablets, sachet or suspension. J Antimicrob Chemother. 1996 Jun;37 Suppl C:37-44. PubMed
  • 13. Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial. Br J Ophthalmol. 2015 Feb;99(2):199-204.
  • 14. Kim JE, Park AY, Lee SY, Park YL, Whang KU, Kim HJ. Comparison of the Efficacy of Azithromycin Versus Doxycycline in Acne Vulgaris: A Meta-Analysis of Randomized Controlled Trials. Ann Dermatol. 2018 Aug;30(4):417-426.

Published: January 10, 2014
Last updated: August 12, 2018


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