Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin

Am J Med. 2008 Oct;121(10):903-8. doi: 10.1016/j.amjmed.2008.04.042.


Background: Benzathine penicillin G is the treatment of choice for infectious syphilis, but tetracycline and doxycycline are believed to be effective second-line treatments. The objective of this study was to assess the serological response from treatment of primary syphilis with benzathine penicillin compared with doxycycline or tetracycline.

Methods: We examined rapid plasma reagin serological test results of all first-time primary syphilis patients in Alberta, Canada from 1980 to 2001 and compared treatment with single dose of penicillin with 14-day course of oral doxycycline (100 mg twice a day) or oral tetracycline (500 mg 4 times a day). Serological treatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titer within 6 months, or > or =8-fold decrease within 12 months, or > or =16-fold decrease by 24 months. The median time to successful response was estimated, and factors associated with treatment success were identified by unadjusted logistic regression.

Results: Of the 445 primary syphilis cases with available treatment outcome data, 420 (94.4%) received penicillin and 25 (5.6%) received doxycycline/tetracycline. The serological treatment success rate was 97.4% in the penicillin group (409/420) and 100% in the doxycycline/tetracycline group (25/25), and not significantly different. The estimated median time to serological treatment success was 72.0 days (mean=101.7, range 10-603) in penicillin and 43.0 days (mean=78.6, range 15-334) in doxycycline/tetracycline-treated patients; however, this difference was not statistically significant (P=0.16).

Conclusion: Doxycycline/tetracycline had a similarly high serological treatment success rate when compared with penicillin in the treatment of primary syphilis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Cohort Studies
  • Doxycycline / therapeutic use*
  • Female
  • Humans
  • Male
  • Penicillin G Benzathine / therapeutic use*
  • Retrospective Studies
  • Serologic Tests
  • Syphilis / blood
  • Syphilis / drug therapy*


  • Anti-Bacterial Agents
  • Doxycycline
  • Penicillin G Benzathine