Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial

Clin Infect Dis. 2021 Sep 7;73(5):824-831. doi: 10.1093/cid/ciab153.


Background: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective.

Methods: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants.

Results: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16-36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9-31%; P < .001).

Conclusions: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM.

Clinical trials registration: NCT03608774.

Keywords: Chlamydia trachomatis; rectal infection; sexual and gender minorities; sexually transmitted diseases; therapeutics.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / therapeutic use
  • Chlamydia Infections* / drug therapy
  • Chlamydia trachomatis
  • Double-Blind Method
  • Doxycycline / therapeutic use
  • Homosexuality, Male
  • Humans
  • Male
  • Sexual and Gender Minorities*


  • Anti-Bacterial Agents
  • Azithromycin
  • Doxycycline

Associated data