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Journal Club: Meta-analysis of Azithromycin versus Doxycycline for genital chlamydia infection

Article reviewed

F. Y. S. Kong, S. N. Tabrizi, M. Law, L. A. Vodstrcil, M. Chen, C. K. Fairley, R. Guy, C. Bradshaw, and J. S. Hocking. Azithromycin Versus Doxycycline for the Treatment of Genital Chlamydia Infection: A Meta-analysis of Randomized Controlled Trials. Clinical Infectious Diseases 2014;59(2):193–205.

Purpose of the study

Currently, the United States CDC, Public Health Canada, and BC guidelines all recommend either azithromycin 1g as a single dose OR doxycycline 100mg BID for 7 days, as treatment for genital chlamydia.

The last review of studies evaluating azithromycin and doxycycline treatment for genital chlamydia took place in 2002.[1] The review found a success rate for azithromycin and doxycycline of 97% and 98%, respectively. These were not significantly different.

Diagnostic technology has changed since 2002, with nucleic acid amplification tests being used instead of culture or enzyme immunoassays. Also, higher failure rates for genital chlamydia infections have been reported from more recent studies (8%).[2,3]

This study was conducted to update the previous meta-analysis from 2002 and better determine if azithromycin or doxycycline is superior for the treatment of genital chlamydia.


Only randomized controlled trials, published up to December 31st, 2013, were included. Papers comparing the efficacy of azithromycin with doxycycline for treating genital (urethral or cervical) chlamydia infection in men and women were selected for review. Only papers evaluating men or women ≥15 years old, urethral or cervical sites, microbiologically proven infections, with test of cure within 3 months of treatment were considered. Papers were excluded if patients had prostatitis or pelvic inflammatory disease.

The primary outcome was the difference in treatment efficacy (efficacy for doxycycline minus efficacy for azithromycin) at the last follow-up, confirmed by a microbiological cure. This was defined as a negative chlamydia test result at the last follow-up visit, within 3 months of treatment. Fixed effects and random effects modeling was used to analyze the studies, with both reported.

Key findings

A total of 23 papers were included in the meta-analysis. There were 1,147 and 912 patients evaluated for azithromycin and doxycycline efficacy, respectively.

Cure rates were:

  • Azithromycin – Fixed effect (96.2%; 95% CI, 94.9%–97.5%)
  • Azithromycin – Random effect (94.3%; 95% CI, 91.8%–96.8%)
  • Doxycycline – Fixed effect (97.4%; 95% CI, 96.2%–98.7%)
  • Doxycycline – Random effect (97.1%; 95% CI, 95.6%–98.6%)

Implications for practice

The meta-analysis showed a small difference of between 1.5% and 2.6% in favor of doxycycline for the treatment of urogenital chlamydia infection for men and women. In addition, there was about a 7% increased efficacy for doxycycline for the treatment of symptomatic urethral infection in men.

It is unclear if this difference in treatment efficacy is due to emerging resistance to azithromycin for Chlamydia isolates. However, resistance has been reported in studies previously.[5,6,7] The increased efficacy of doxycycline may also be due to delayed sexual activity, compared to azithromycin, due to reluctance to resume while on the 7 day course of doxycycline therapy.

From this study, both azithromycin and doxycycline have cure rates ≥95% and both could be used as first line agents, according to WHO recommendations for empiric therapy agents (8). However, certain sub-populations may benefit from doxycycline being used as the first line agent:

  • Men
  • Symptomatic patients (particularly symptomatic men)

Further information

Pubmed abstract: http://www-ncbi-nlm-nih-gov.ezproxy.library.ubc.ca/pubmed/24729507


  1. Lau, CY and 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.
  2. Batteiger BE, Tu W, Ofner S, et al. Repeated Chlamydia trachomatis genital infections in adolescent women. J Infect Dis 2010; 201:42–51.
  3. Golden MR, Whittington WLH, Handsfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection. N. Engl. J. Med. 2005; 352:676–85.
  4. Schwebke JR, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens—a randomized clinical trial. Clin. Infect. Dis. 2011; 52:163–70.
  5. ones RB, Van Der Pol B, Martin DH, et al. Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics. J. Infect. Dis. 1990; 162:1309–15.
  6. Wang S, Papp J, Stamm W, et al. Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J. Infect. Dis. 2005; 191:917–23.
  7. Horner P. The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection. Sex. Transm. Infect. 2006; 82: 340–3.
  8. World Health Organization. Guidelines for the management of sexually transmitted infections. Geneva, Switzerland: WHO, 2003.