Man in pink shirt using mobile phone to look up azithromycin vs. doxycycline

Azithromycin vs. Doxycycline: What's the Difference?

Written on July 18, 2023 by Lori Mulligan, MPH. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

Table of contents

Azithromycin and doxycycline are two antibiotics used to treat many different bacterial infections, including several sexually transmitted diseases (STDs).

Azithromycin has the distinct advantage of once-daily dosing; however, commonly reported side effects include diarrhea, loose stools, and nausea. Other side effects include abdominal pain and vomiting.

Doxycycline treats and prevents a wide range of bacterial infections as well. It’s a common antibiotic that treats conditions like urinary tract infections, intestinal infections, respiratory infections, and others.

It too has side effects, such as [1]:

  • Allergic reactions — skin rash, itching, hives, swelling of the face, lips, tongue, or throat
  • Increased pressure around the brain — severe headache, change in vision, blurry vision, nausea, and vomiting
  • Joint pain
  • Pain or trouble swallowing
  • Redness, blistering, peeling, or loosening of the skin, including inside the mouth
  • Fever
  • Unusual vaginal discharge, itching, or odor

Doxycycline also has side effects that usually do not require medical attention:

  • Change in tooth color
  • Diarrhea
  • Headache
  • Heartburn
  • Nausea

Patient Reviews

Azithromycin has an average rating of 6.8 out of 10 from a total of 1,284 ratings on Fifty-six percent of reviewers reported a positive effect, while 21% reported a negative effect.

Doxycycline is an effective antibiotic that treats a wide range of infections. Doxycycline has an average rating of 6.4 out of 10 from a total of 1615 ratings on Fifty percent of reviewers reported a positive effect, while 27% reported a negative effect.[2]

So, which one is better? Let’s look at a few infectious bacterial diseases and see which antibiotic is recommended for treatment.


Currently, single-dose azithromycin is recommended over multi-dose doxycycline as a treatment for chlamydial infection. However, consideration should be given to re-evaluating azithromycin as the standard treatment for genital chlamydia in women because when the possibility of autoinoculation is taken into account, doxycycline effectiveness may be 97% compared to just 82% for azithromycin. Even with imperfect adherence, doxycycline is more effective in treating genital and chlamydia rectal infections.

Doxycycline is a more effective treatment for rectal chlamydia than azithromycin. In a study of rectal chlamydia in men who have sex with men, 100% of patients treated with doxycycline achieved microbiologic cure vs. 74% of those treated with azithromycin.[3]

Private STD consultations

For people with uncomplicated genital chlamydia, the WHO STI guidelines suggest one of the following options:

  • 1 g azithromycin orally as a single oral dose
  • 100 mg doxycycline orally twice a day for seven days

While good practice based on evidence of large net benefit dictates which patients should be treated for chlamydial infection, the choice of treatment may depend on the convenience of dosage, the cost and quality of the medicines in different settings, and equity considerations.

When a high value is placed on reducing costs, doxycycline in a standard dose may be the best choice; when a high value is placed on convenience, azithromycin in a single dose may be the best choice. A delayed-release formulation of doxycycline may be an alternative to twice daily dosing of doxycycline, but the high cost of the delayed-release formulation may prohibit its use.[4]

Acute Rhinosinusitis

Macrolides, such as azithromycin, are not recommended due to high levels of antibiotic resistance to Streptococcus pneumoniae (~40%). For penicillin-allergic patients, doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) are recommended as alternative agents.[5]

Acne Vulgaris

Acne vulgaris is one of the chronic, common dermatological skin diseases with inflammatory lesions prevalent among adolescents. The management of acne vulgaris is primarily pharmacotherapy comprising both topical and systemic anti-inflammatory and antimicrobial agents.

There are several studies regarding recommendations, guidelines, efficacy, tolerability, and outcomes of therapies used in acne vulgaris, but hardly any studies comparing the cost-effectiveness of this combination of topical and oral antimicrobials in the treatment of moderate to severe acne vulgaris in the United States. However, a recent comparison of azithromycin and doxycycline did just that. The study found that both drugs effectively reduced the lesion count but required long-term treatment; however, azithromycin was more cost-effective than doxycycline. Doxycycline was also slightly less effective.[6]

How Everlywell Can Help

You can benefit from STD treatment online with a licensed healthcare provider via Everlywell's telehealth option. This will let you receive the fast and discreet STD care you deserve.

Doxycycline for STDs: What It Is and How It Works

Amoxicillin for Chlamydia: Key Points to Know

Can You Buy Azithromycin Over The Counter?


  1. Doxycycline injection. Cleveland Clinic. Accessed on July 14, 2023.
  2. Comparing Azithromycin vs Doxycycline. Accessed on July 13, 2023.
  3. Craig, A.P., Kong, F.Y., Yeruva, L. et al. Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modeling the impact of autoinoculation from the gastrointestinal tract to the genital tract. BMC Infect Dis 15, 200 (2015).
  4. WHO Guidelines for the Treatment of Chlamydia trachomatis. Geneva: World Health Organization; 2016. 4, RECOMMENDATIONS FOR TREATMENT OF CHLAMYDIAL INFECTIONS. Available from: Accessed on July 14, 2023.
  5. Adult Outpatient Treatment Recommendations. Centers for Disease Control and Prevention. Accessed on July 14, 2023.
  6. Apoorval GK , Amoolya D. A comparison of cost-effectiveness between doxycycline and azithromycin with topical clindamycin in the treatment of patients with moderate to severe acne vulgaris: Prospective, randomized study. National Journal of Physiology, Pharmacy and Pharmacology. February 13, 2020.
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