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Syphilis diagnosis, staging and treatment

CDC stage-specific serology, penicillin treatment, pregnancy, neurologic and ocular escalation, partner services and response monitoring.

JurisdictionUnited States
Source check2026-08-20
Clinical reviewiatroX editorial team · Clinical editorial review · reviewed 2026-08-20 · due 2027-08-20
AudienceUnited States healthcare professionals
This is an iatroX educational summary of named United States sources, not an official guideline. It does not replace the complete source documents, local policy, specialist advice or clinical judgement. Use the named authority, current FDA labeling, applicable state law, payer rules and local protocol where relevant.

Scope of this summary

Adolescents and adults evaluated for acquired syphilis, including pregnancy and people with HIV. Congenital syphilis and detailed infant management require their dedicated CDC pathway. Treatment must be selected from stage, symptoms and neurologic, ocular or otic involvement.
sources for this section:CDC STI Guidelines 2021

The Bottom Line

  • Diagnose with both a nontreponemal and a treponemal test and interpret the sequence, titer and prior treatment together; one reactive assay alone does not establish stage or treatment need.
  • Stage from examination, symptom and exposure history and prior serology: primary, secondary and early latent disease differ from late latent or unknown-duration infection in treatment duration and partner look-back.
  • Treat primary, secondary and early latent syphilis in adults with benzathine penicillin G 2.4 million units intramuscularly once; late latent or unknown-duration disease requires 7.2 million units total as three weekly 2.4-million-unit doses.
  • Evaluate neurologic, ocular and otic symptoms at every stage. Neurosyphilis, ocular syphilis and otosyphilis use an aqueous penicillin pathway and specialist coordination, not benzathine penicillin alone.
  • Penicillin is the only proven treatment during pregnancy; desensitize and treat a pregnant patient with allergy, manage missed-dose timing strictly and coordinate fetal and congenital-syphilis evaluation.
sources for this section:CDC STI Guidelines 2021

Practical clinical workflow

1
Take a complete sexual, pregnancy, neurologic, visual, hearing and prior-treatment history; examine skin, mouth, lymph nodes and genital or perianal sites and perform a neurologic assessment when indicated.
2
Obtain a quantitative nontreponemal titer and treponemal assay using the laboratory’s traditional or reverse algorithm; test for HIV and other STIs and consider PrEP when HIV is excluded.
3
Assign stage conservatively from reliable evidence, select the exact CDC regimen and document product as Bicillin L-A rather than a non-equivalent penicillin preparation.
4
Warn about the Jarisch–Herxheimer reaction, counsel abstinence until the source-defined period after patient and partner treatment, and engage confidential health-department partner services.
5
Repeat quantitative nontreponemal testing at the stage- and HIV-specific intervals, compare with the same test where possible and evaluate reinfection, failure or neurologic disease when the titer response is inadequate.
sources for this section:CDC STI Guidelines 2021

Safety boundaries and escalation

  • Visual change, eye pain, hearing loss, tinnitus, cranial neuropathy, meningitic symptoms, stroke syndrome, altered cognition or sensory or gait abnormality requires prompt neurologic, ophthalmic or otologic evaluation and the neurosyphilis pathway.
  • Never substitute Bicillin C-R or another long-acting mixture for benzathine penicillin G in syphilis treatment; verify the formulation during shortages or temporary importation programs.
  • A pregnant patient with syphilis needs immediate treatment and obstetric or public-health coordination; do not delay for a specialist appointment or use an unproven nonpenicillin alternative.
  • A fourfold titer rise after treatment suggests reinfection or failure and requires reassessment, HIV testing and consideration of cerebrospinal-fluid evaluation according to symptoms and exposure.
sources for this section:CDC STI Guidelines 2021

Localization

CDC STI Treatment Guidelines and state or local health departments define the US pathway. Syphilis reporting, prenatal screening statutes and partner services vary by jurisdiction, and the 2026 benzathine-penicillin supply notice must be checked.
sources for this section:CDC STI Guidelines 2021

Source documents

Use the linked source documents for complete recommendations, evidence grading, exclusions and implementation detail.

  1. Centers for Disease Control and PreventionSexually Transmitted Infections Treatment Guidelines, 2021MMWR Recomm Rep 2021;70(No. RR-4):1–187 · Current CDC STI treatment guideline portal, including published erratum and 2026 supply notices · published 2021-07-23 · accessed 2026-08-20
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