What is the treatment for tertiary syphilis (stage 3 syphilis)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

The recommended treatment for stage 3 (tertiary) syphilis is penicillin G, specifically benzathine penicillin G administered as 2.4 million units intramuscularly once weekly for three consecutive weeks (total of 7.2 million units). For patients with neurosyphilis or ocular involvement, the preferred regimen is aqueous crystalline penicillin G 3-4 million units intravenously every 4 hours for 10-14 days. For penicillin-allergic patients, doxycycline 100 mg orally twice daily for 28 days can be used, though desensitization to penicillin is preferred when possible. Treatment should be initiated promptly as tertiary syphilis can cause serious complications including damage to the heart, blood vessels, brain, and other organs. Following treatment, patients need clinical and serological follow-up at 6,12, and 24 months to ensure adequate response. The effectiveness of penicillin in treating syphilis is due to its ability to disrupt the cell wall synthesis of Treponema pallidum, the bacterium causing syphilis, as supported by studies such as 1 and 1. Patients should abstain from sexual contact until treatment is complete and should notify all sexual partners who may need testing and treatment.

Some key points to consider in the treatment of stage 3 syphilis include:

  • The importance of prompt treatment to prevent long-term complications, as emphasized in 1 and 1.
  • The need for careful consideration of treatment options in patients with penicillin allergy, as discussed in 1.
  • The role of clinical and serological follow-up in ensuring adequate response to treatment, as highlighted in 1 and 1.

Overall, the treatment of stage 3 syphilis requires careful consideration of the patient's individual needs and circumstances, as well as adherence to established treatment guidelines, such as those outlined in 1 and 1.

From the Research

Treatment for Stage 3 Syphilis

There are no specific studies provided that directly address the treatment for stage 3 syphilis. However, the following information can be gathered from the available studies:

  • The studies primarily focus on the treatment of early syphilis, with benzathine penicillin G being the recommended treatment 2, 3, 4.
  • Alternative treatments such as doxycycline and ceftriaxone have been shown to be effective in treating early syphilis 3, 4, 5.
  • Enhanced antibiotic therapy, including the addition of doxycycline and ceftriaxone to benzathine penicillin G, has been shown to be more effective than standard treatment in achieving serological cure 6.
  • The following key points can be noted:
    • Benzathine penicillin G is the recommended treatment for early syphilis 2.
    • Doxycycline and ceftriaxone can be used as alternative treatments for early syphilis 3, 4, 5.
    • Enhanced antibiotic therapy may be more effective in achieving serological cure 6.
    • Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of adult syphilis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2011

Research

Doxycycline compared with benzathine penicillin for the treatment of early syphilis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2006

Research

A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017

Research

A new enhanced antibiotic treatment for early and late syphilis.

Journal of global antimicrobial resistance, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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