Antibiotics for syphilis


Penicillin is the antibiotic most commonly used to treat syphilis. Penicillin is usually given as a shot (injection).

If you are allergic to penicillin, your doctor may prescribe another antibiotic, such as doxycycline, tetracycline, ceftriaxone, or azithromycin, for the earlier stages of syphilis. Later stages of syphilis may require treatment with penicillin.

Penicillin is the only antibiotic that should be used during pregnancy. If you are pregnant and think you may be allergic to penicillin, discuss your allergy with your doctor.

How It Works

Antibiotics destroy the bacteria that cause syphilis.

Why It Is Used

Antibiotics are indicated if you have a positive blood test for syphilis during routine screening or have symptoms suggestive of syphilis. Exposed sex partners of a person with syphilis and babies born to women who have syphilis also need treatment.

The amount of antibiotics used and how often the medicine is taken are based on the stage of the illness. For example, if neurosyphilis is present, you will need to receive antibiotics for 10 days to 2 weeks.

How Well It Works

Treatment with penicillin cures most cases of syphilis in any stage. Antibiotics prevent further complications of syphilis but may not reverse damage that has already occurred.

A follow-up exam and a blood test for cure should be done at 6 and 12 months after the antibiotics are given (and may be done at 24 months after latent syphilis) to be sure the infection is cured.

If human immunodeficiency virus (HIV) infection was also present at the time of treatment, follow-up exams and blood tests should be done at 3, 6, 9, 12, and 24 months.1

Syphilis passed to a baby from the mother (congenital syphilis) may be prevented if pregnant women are treated before the 16th to 18th weeks of pregnancy. Treatment after 16 to 18 weeks will cure the infection and stop the damage to the baby. But it may not reverse damage already caused by the infection.

Side Effects

A Jarisch-Herxheimer reaction is a fairly common reaction to antibiotic treatment of syphilis that involves fever and headache. It may occur up to 8 hours after the first treatment of early syphilis. Oral steroids, such as prednisone, or nonsteroidal anti-inflammatory drugs (NSAIDs) taken before the antibiotic is given may prevent the Jarisch-Herxheimer reaction.2 But most experts do not recommend routine use of this approach, because the reaction is usually mild and of limited duration.

The reason the Jarisch-Herxheimer reaction occurs is not clear. But it may be caused by the toxins released from the syphilis bacteria as they are destroyed by antibiotics. A Jarisch-Herxheimer reaction is not the same as an allergic reaction to penicillin.

Pregnant women in the second half of pregnancy have an increased risk for premature labor and fetal distress if they have a Jarisch-Herxheimer reaction. But pregnant women who have syphilis should still be treated, because congenital syphilis is more likely to cause fetal death. If you are pregnant and have symptoms of this reaction, tell your doctor right away.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Guidelines for the treatment of syphilis and other sexually transmitted diseases are updated by the U.S. Centers for Disease Control and Prevention (CDC) on an ongoing basis.

Antibiotic treatment can cure syphilis. And it can prevent complications. The complications of tertiary-stage or congenital syphilis may not be reversed with treatment. But the progression of the disease will be stopped.

Penicillin is the preferred drug for treating syphilis. And penicillin is the standard therapy for the treatment of neurosyphilis, congenital syphilis, or syphilis acquired or detected during pregnancy. But other antibiotics (such as ceftriaxone) may be used.

Penicillin is the only proven therapy that has been widely used for neurosyphilis, congenital syphilis, or syphilis during pregnancy. When syphilis is treated with a drug other than penicillin, closer follow-up is needed to monitor for cure or relapse.

Penicillin passes into breast milk in small amounts. But it is not usually harmful to a nursing baby. Doxycycline and tetracycline both pass into breast milk and may affect the bone and tooth development of a nursing baby. If you are breast-feeding a baby, do not take any of these medicines without first talking to your doctor.

The CDC recommends that a follow-up exam and a blood test for cure be done at 6 and 12 months after antibiotics are given (a test may also be done at 24 months in latent syphilis) to be sure the infection has been cured. Follow-up exams and tests are recommended at 3, 6, 9, 12, and 24 months if HIV infection was also present at the time of treatment.1

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  1. Centers for Disease Control and Prevention (2006). Syphilis section of Sexually Transmitted Diseases Treatment Guidelines 2006. MMWR, 55(No. RR-11): 22–30. Available online:
  2. Augenbraun M (2006). Syphilis and the nonvenereal treponematoses. In DC Dale, DD Federman, eds., ACP Medicine, section 7, chap. 6. New York: WebMD.

Last Updated: September 30, 2009

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