What is syphilis?

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Last updated: April 14, 2025View editorial policy

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From the Guidelines

Syphilis is a sexually transmitted infection that should be treated with penicillin G, with the specific regimen depending on the stage of infection, to prevent morbidity, mortality, and improve quality of life. The most recent and highest quality study 1 recommends that pregnant women be screened for syphilis infection, and if diagnosed, be treated with parenteral benzathine penicillin G. For primary, secondary, or early latent syphilis (less than one year), a single intramuscular injection of benzathine penicillin G 2.4 million units is recommended. For late latent syphilis or syphilis of unknown duration, three weekly doses of benzathine penicillin G 2.4 million units are needed. Neurosyphilis requires intravenous aqueous crystalline penicillin G 18-24 million units daily for 10-14 days. Some key points to consider when treating syphilis include:

  • The importance of screening for syphilis infection in pregnant women, as it can prevent stillbirth, neonatal death, bone deformities, and neurologic impairment 1
  • The use of nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test or the rapid plasma reagin (RPR) test, for initial screening, followed by a confirmatory fluorescent treponemal antibody absorbed test or Treponema pallidum particle agglutination (TPPA) test 1
  • The potential harms of screening and treatment, including false-positive results, unnecessary anxiety, and harms of antibiotic use, but the benefits of screening and treatment outweigh these harms 1
  • The importance of follow-up blood tests to confirm cure after treatment, as syphilis can progress through stages if left untreated, including primary (painless sore), secondary (rash, fever), latent (no symptoms), and tertiary (severe organ damage) 1.

From the Research

Syphilis Treatment

  • The primary treatment for early syphilis is a single dose of 2.4 million units of benzathine penicillin G, with reported treatment success rates of 90% to 100% 2.
  • Alternative treatments, such as azithromycin, have been studied, with a single 2-g oral dose showing promise as an effective treatment for early syphilis 3, 4.
  • However, the use of azithromycin is limited due to reported increases in resistance, making it not recommended for routine use 5.

Treatment Response

  • Treatment response is typically monitored through serologic tests, with a decline in rapid plasma reagin (RPR) titers indicating successful treatment 3, 2.
  • The "serofast state," where patients remain seropositive after treatment, is a common occurrence, but does not necessarily indicate treatment failure 2.
  • Serologic response to treatment should be evident by 6 months in early syphilis, but may be slower (12-24 months) for latent syphilis 2.

Special Populations

  • For HIV-infected individuals, a single dose of benzathine penicillin G is recommended, with some studies suggesting that multiple-dose treatment may not be necessary 6, 2.
  • Pregnant women should be treated with penicillin as first-line therapy, despite limited evidence defining treatment for this population 2.
  • Neurosyphilis treatment requires cerebrospinal fluid (CSF) examination, and treatment should be tailored to the individual patient's needs 5.

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

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

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

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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