Management of Adult Syphilis: Key Questions to Inform the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines

Clin Infect Dis. 2015 Dec 15;61 Suppl 8:S818-36. doi: 10.1093/cid/civ714.


A panel of experts generated 8 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. Penicillin is the drug of choice to treat syphilis. Doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There is no added benefit to enhanced antimicrobial therapy when treating human immunodeficiency virus-infected persons with syphilis. If a patient misses a dose of penicillin in a course of weekly therapy for late syphilis, clinical experience suggests that an interval of 10-14 days between doses might be acceptable before restarting the sequence of injections. Pharmacologic considerations suggest that an interval of 7-9 days between doses, if feasible, may be more optimal. Missed doses are not acceptable for pregnant women. A cerebrospinal fluid examination to diagnose neurosyphilis is recommended in persons diagnosed with tertiary syphilis (eg, cardiovascular syphilis or late benign syphilis), persons with neurological signs or symptoms consistent with neurosyphilis, and asymptomatic persons whose serological titers do not decline appropriately following recommended therapy and in whom reinfection is ruled out. Infection and reinfection rates, particularly among men who have sex with men, are high. Frequent serological screening of this population appears to be the most cost-efficient intervention. The Centers for Disease Control and Prevention continues to recommend the use of the traditional rapid plasma reagin-based screening algorithm. The positive predictive value for syphilis associated with an isolated unconfirmed reactive treponemal chemiluminescence assay or enzyme immunoassay is low if the epidemiological risk and clinical probability for syphilis are low. Among pregnant women with serodiscordant serologies (positive treponemal tests and a negative nontreponemal test), the risk of vertical transmission from mother to infant is low. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.

Keywords: CDC; Centers for Disease Control and Prevention; neurosyphilis; syphilis; treatment guidelines.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Centers for Disease Control and Prevention, U.S.
  • Disease Management
  • Doxycycline / therapeutic use
  • Drug Administration Schedule
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Humans
  • Infectious Disease Transmission, Vertical
  • Male
  • Neurosyphilis / diagnosis
  • Neurosyphilis / microbiology
  • Penicillins / administration & dosage
  • Penicillins / therapeutic use
  • Practice Guidelines as Topic
  • Pregnancy
  • Syphilis / complications
  • Syphilis / diagnosis*
  • Syphilis / drug therapy*
  • Syphilis / prevention & control
  • Syphilis Serodiagnosis
  • United States


  • Anti-Bacterial Agents
  • Penicillins
  • Doxycycline