How Syphilis Is Treated

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Syphilis, a sexually transmitted infection (STI), is fairly common—affecting more than 120,000 people each year. The mainstay treatment for this STI is penicillin, but other types of antibiotics may be appropriate as well.

Learn more about syphilis and the potential treatment options your healthcare provider may prescribe if you or your partner become infected.

syphilis symptoms
Illustration by Joshua Seong. © Verywell, 2018.


Syphilis treatment often requires a single injection. The course of therapy is largely directed by the stage of infection (primary, secondary, latent, tertiary) and other contributing factors. Of note, the primary and secondary stages of syphilis are the most infectious.

Penicillin G is considered the drug of choice. In most cases, the drug will be delivered with an intramuscular (IM) injection, usually in the gluteal muscle (buttocks). In severe cases, the drug may be given intravenously (via IV).

Penicillin Allergy

For people allergic to penicillin, alternative drugs such as doxycycline, tetracycline, azithromycin, and ceftriaxone may be used. However, treatment options are more limited for certain types of syphilis infection.

Neurosyphilis (a late-stage complication affecting the brain and central nervous system) can be treated with penicillin or ceftriaxone, if there is a penicillin allergy. Penicillin is the only option for congenital syphilis (where the infection is passed from mother to child during pregnancy).

Follow-Up Testing After Treatment

Unlike some bacterial infections in which people are presumed cured after completing therapy, people with syphilis need to undergo follow-up tests to confirm that the infection has cleared. While a person is generally not considered contagious 24 hours after completing treatment, some healthcare providers will recommend abstinence until follow-up tests have been completed.

Additionally, serious neurological and eye complications can occur and persist even after the infection has been treated.

Treatment Recommendations

In 2021, the Centers for Disease Control and Prevention (CDC) issued updated recommendations on the treatment of syphilis:

  • Primary, secondary, or early latent syphilis: A one-time intramuscular injection of penicillin G is the treatment of choice. The preparation of penicillin G used (i.e., benzathine, aqueous procaine, or aqueous crystalline), dose, and duration of treatment are based on the stage and clinical manifestations of the disease.
  • Late latent syphilis, latent syphilis of unknown duration, or tertiary syphilis: Three intramuscular injections of penicillin G delivered a week apart is the standard treatment. In this phase, selection of the appropriate penicillin preparation is important because T. pallidum can reside in parts of the body (e.g., the central nervous system or the fluid around the eye) that certain forms of penicillin can't reach. 
  • Neurosyphilis or ocular syphilis: IV penicillin G is delivered over 10 to 14 days in a hospital setting OR intramuscular penicillin G plus oral probenecid (both for 10 to 14 days) is given as an alternative option.

The recommendations for treatment of primary and secondary syphilis apply to infants and children, as well as adults. Infants and children age one month and older who are diagnosed with latent syphilis should be managed by a pediatric infectious disease specialist and undergo a cerebrospinal fluid (CSF) examination. Because the time between primary infection and tertiary syphilis is very long (often more than 10 to 20 years), advanced syphilis is exceedingly rare in children.

While penicillin G is considered effective in clearing a syphilis infection, some people may require additional treatments if follow-up tests suggest that the infection hasn't cleared.

Pregnant Women

The best treatment for syphilis diagnosed during pregnancy is also penicillin G.

If a mother is allergic to penicillin, her healthcare provider can take steps to desensitize her with a series of allergy shots. This would involve exposing the mother to smaller amounts of penicillin and increasing the dosage gradually to build tolerance so that she can eventually be treated with the antibiotic.


In recent years, there have been growing concerns about the threat of antibiotic drug resistance in treating sexually transmitted diseases.

Many of the concerns stemmed from the use of oral antibiotics in treating gonorrhea, the practice of which led to widespread resistance and the subsequent ineffectiveness of the previously used combination of injectable and oral antibiotics. As a result, gonorrhea is now treated with a single intramuscular dose of ceftriaxone.

Thus far, there have been no indications of this happening with syphilis and penicillin. There have, however, been signs of a developing resistance to azithromycin, mostly related to resistant strains of syphilis that first emerged in the 1950s with the introduction of antibiotics.

So, while epidemiologists continue to monitor for signs of antibiotic resistance, penicillin should be considered the safest and most reliable means of treating syphilis.

Sexual Partners

According to the CDC, anyone exposed through sexual contact with a person who has primary, secondary, or early latent syphilis should be treated according to the following recommendations:

  • If you had sexual contact with a person within <90 days before their diagnosis, you should be treated presumptively for early syphilis, even your test results are negative.
  • If you had sexual contact with a person >90 days before their diagnosis and testing is not available and follow-up is a concern, you should be treated. If your testing is negative, then you don't need treatment.

The following sex partners of people who have syphilis are considered at risk for infection and should be confidentially notified of the exposure and need for evaluation:

  • Partners who have had sexual contact within three months plus the duration of symptoms with someone who received a diagnosis of primary syphilis
  • Partners who have had sexual contact within six months plus duration of symptoms with someone who has secondary syphilis
  • Partners who have had sexual contact within one year with someone who has early latent syphilis

Frequently Asked Questions

  • How is syphilis treated?

    An intramuscular injection of penicillin G is the preferred treatment for all stages of syphilis. Generally, a single shot of long-acting benzathine penicillin G will cure a person of primary, secondary, or early latent syphilis. Late latent and tertiary syphilis are treated with three doses given at one-week intervals.

  • How is syphilis treated if you're allergic to penicillin?

    Even when there is an allergy, penicillin G is still the treatment of choice. Your healthcare provider may do allergy testing or other tests to verify if there is a true high-risk allergy to penicillin. Most patients are able to safely get the standard treatment of penicillin. In rare cases, there are other options to treat with oral and IV antibiotics, which can be tailored to the stage of syphilis.

  • How is syphilis treated during pregnancy?

    Penicillin G is the only recommended treatment. Pregnant persons who are allergic to penicillin would need to undergo penicillin desensitization in a hospital.

  • Do sex partners exposed to syphilis always need treatment?

    Yes, always. If you have had sex with someone within 90 days of their syphilis diagnosis, you would be presumptively treated even if your own syphilis test is negative.

  • How long is syphilis contagious after treatment?

    You would need to abstain from sex until the syphilis sores (chancres) are completely healed. Persons with vaginas or those who were exposed through anal sex may need a medical examination, as the sores may be internal and not readily seen.

  • Why is follow-up testing needed after syphilis treatment?

    Follow-up testing is used to ensure that the treatment worked. Syphilis antibody levels will be elevated after treatment, and they will gradually subside over time. A four-fold decrease in antibodies after one year is considered a treatment success. Most people are advised to undergo retesting six to 12 months after the completion of treatment.

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6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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