Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis

Ann Intern Med. 1999 Sep 21;131(6):434-7. doi: 10.7326/0003-4819-131-6-199909210-00007.


Background: Preventive therapy is an important element of syphilis control efforts. No currently recommended, single-dose alternatives to penicillin G benzathine are available for treatment of incubating syphilis.

Objective: To evaluate the use of a single 1.0-g dose of azithromycin for treatment of persons recently exposed to sexual partners with infectious syphilis.

Design: Single-center, open-label, randomized pilot study to compare azithromycin with penicillin G benzathine therapy. Participants were evaluated serologically for 3 months.

Setting: Sexually transmitted disease clinic in Birmingham, Alabama.

Participants: 96 participants who in the preceding 30 days had been exposed to partners with infectious syphilis through sexual intercourse.

Measurements: Syphilis prevention, as indicated by nonreactive serologic tests (rapid plasma reagin and fluorescent treponemal antibody-absorbed), throughout the 3-month follow-up.

Results: Among 96 participants enrolled, none of 40 evaluable persons in the azithromycin group and none of 23 evaluable persons in the penicillin group developed evidence of syphilis. Significantly more penicillin-treated participants (21 of 44 [48%]) than azithromycin-treated participants (12 of 52 [23%]) became nonevaluable during follow-up (P = 0.01).

Conclusion: A single 1.0-g dose of azithromycin seems to be efficacious for prevention of syphilis in persons exposed to infected sexual partners.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Azithromycin / administration & dosage*
  • Disease Transmission, Infectious / prevention & control*
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Penicillin G Benzathine / administration & dosage*
  • Penicillins / administration & dosage*
  • Pilot Projects
  • Syphilis / prevention & control*
  • Syphilis / transmission*
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Penicillins
  • Azithromycin
  • Penicillin G Benzathine