Treatment of syphilis
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CDC STI Treatment Guidelines syphilis treatment benzathine penicillin G neurosyphilis pregnancy
Syphilis treatment in adults
Treatment depends on the stage and whether there is neurologic, eye, or ear involvement. Penicillin remains the preferred treatment, with no documented clinical resistance of T. pallidum to penicillin.
| Clinical stage | Recommended regimen |
|---|---|
| Primary, secondary, or early latent syphilis (acquired within the last year) | Benzathine penicillin G 2.4 million units IM once |
| Late latent syphilis, latent syphilis of unknown duration, or tertiary syphilis without neurosyphilis | Benzathine penicillin G 2.4 million units IM weekly for 3 doses. Total 7.2 million units |
| Neurosyphilis, ocular syphilis, or otosyphilis | Aqueous crystalline penicillin G 18-24 million units/day IV, as 3-4 million units every 4 hours or continuous infusion, for 10-14 days |
The current CDC regimen summary is available in its syphilis pocket guide. Benzathine penicillin is suitable for uncomplicated disease but does not achieve adequate CSF concentrations, so it must not be used alone for neurosyphilis.
Penicillin allergy
For nonpregnant adults with uncomplicated early syphilis, alternatives may include:
- Doxycycline 100 mg orally twice daily for 14 days for early syphilis
- Doxycycline 100 mg orally twice daily for 28 days for late latent or unknown-duration infection
- Ceftriaxone may be considered in selected cases, but the optimal regimen is less certain.
If reliable adherence or follow-up is doubtful, penicillin desensitization followed by penicillin treatment is preferred.
Pregnancy
In pregnancy, penicillin is the only proven treatment that treats maternal infection and adequately treats/prevents fetal infection. A patient allergic to penicillin should undergo desensitization and receive the stage-appropriate penicillin regimen, not doxycycline or another substitute. The CDC primary and secondary syphilis guidance covers this approach.
Follow-up and counseling
- Obtain quantitative RPR or VDRL at baseline, then generally repeat at 6 and 12 months for early syphilis. Late latent infection is usually followed at 6, 12, and 24 months.
- A fourfold fall in nontreponemal titre supports an appropriate response. A fourfold sustained rise suggests reinfection or possible treatment failure and needs reassessment.
- Test for HIV and other STIs.
- Sexual partners need evaluation and often presumptive treatment depending on timing of exposure.
- Avoid sex until lesions have healed and partners have been assessed/treated.
- A Jarisch-Herxheimer reaction can occur within 24 hours after treatment: fever, chills, headache, muscle aches, and temporary worsening of lesions. It is an inflammatory reaction, not penicillin allergy. Seek urgent care for breathing difficulty, facial swelling, or severe allergy symptoms.
For a suspected case, staging from history, examination, and serology should be done by a clinician or sexual-health service before selecting the regimen.
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