What is the recommended treatment for syphilis?

From the Guidelines

The recommended treatment for syphilis is penicillin G, specifically benzathine penicillin G administered as an intramuscular injection, as supported by the most recent and highest quality study 1. For primary, secondary, or early latent syphilis (less than one year duration), a single dose of 2.4 million units is typically sufficient. For late latent syphilis (more than one year duration) or syphilis of unknown duration, the recommended regimen is 2.4 million units of benzathine penicillin G administered intramuscularly once weekly for three consecutive weeks. For neurosyphilis or ocular syphilis, aqueous crystalline penicillin G is preferred, given as 3-4 million units intravenously every 4 hours for 10-14 days. For patients with penicillin allergy, doxycycline (100 mg orally twice daily for 14-28 days) or tetracycline (500 mg orally four times daily for 14-28 days) may be used as alternative treatments, though these are considered less effective, as noted in 1. Penicillin remains the treatment of choice because Treponema pallidum, the bacterium causing syphilis, is highly sensitive to it, and penicillin effectively crosses the blood-brain barrier to treat potential central nervous system involvement, as discussed in 1. Follow-up blood tests are essential to confirm treatment success, typically at 3,6, and 12 months after treatment. Some key points to consider in the treatment of syphilis include:

• The efficacy of penicillin for the treatment of syphilis was well established through clinical experience before the value of randomized controlled clinical trials was recognized, as mentioned in 1.
• Long-acting preparations of penicillin remain the treatment of choice for all stages of syphilis, as supported by more than 40 years of clinical experience and a few recent clinical trials, as discussed in 1.
• Data on 1 versus 3 doses of intramuscular benzathine penicillin G for treatment of early syphilis in human immunodeficiency virus (HIV)–infected patients remain limited, though a phase 4 comparative trial of 1 versus 3 doses of BPG for treatment of early syphilis in subjects with or without HIV infection was initiated in September 2018, as noted in 1.
• Several retrospective studies provide additional reassurance about the efficacy of doxycycline or other tetracyclines for the treatment of early and late latent syphilis, suggesting that they are acceptable alternate agents when penicillin therapy is not feasible, as discussed in 1.
• One randomized trial suggests comparable efficacy for treatment of early syphilis with 1 g/d of intravenous ceftriaxone for 10 days compared with 2 intramuscular doses of 2.4-million units (MU) BPG, as mentioned in 1.
• Azithromycin should not be a recommended treatment for syphilis in the United States due to concerns regarding macrolide resistance, as noted in 1.
• Oral amoxicillin 3 g plus oral probenecid may be a viable option for treatment of syphilis in HIV-infected patients, but there were many limitations to the study, and as such it was felt that there is insufficient data to recommend this regimen, as discussed in 1.
• Treatment of latent syphilis is intended to prevent occurrence or progression of late complications, and although clinical experience supports the effectiveness of penicillin in achieving these goals, limited evidence is available for guidance in choosing specific regimens, as mentioned in 1.
• There is minimal evidence to support the use of nonpenicillin regimens, as noted in 1. It is essential to follow the most recent and highest quality study 1 for the treatment of syphilis to ensure the best possible outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

All cases of penicillin treated syphilis should receive adequate follow-up including clinical and serological examinations. The recommended follow-up varies with the stage of syphilis being treated.

• The recommended treatment for syphilis is penicillin G.
• Penicillin G should be administered with caution and patients should receive adequate follow-up, including clinical and serological examinations.
• The follow-up care may vary depending on the stage of syphilis being treated 2.
• It is essential to note that penicillin G is the recommended treatment, but the specific details of the treatment, such as dosage and administration, are not provided in the given text 3.

From the Research

Treatment Options for Syphilis

The recommended treatment for syphilis typically involves the use of antibiotics. The following are some of the treatment options:

• Benzathine penicillin G: This is the most commonly recommended treatment for syphilis, especially for patients who are not allergic to penicillin 4, 5, 6, 7.
• Azithromycin: This antibiotic has been shown to be effective in treating syphilis, particularly in patients who are allergic to penicillin or have difficulty accessing benzathine penicillin G 4, 6, 7.
• Doxycycline: This antibiotic is often used as an alternative to penicillin, especially in patients who are allergic to penicillin or have other contraindications 5, 8.
• Ceftriaxone: This antibiotic has been shown to be effective in treating syphilis, particularly in patients with HIV infection 8.

Efficacy of Treatment Options

Studies have compared the efficacy of these treatment options:

• A study published in 2002 found that azithromycin was effective in treating syphilis, with a cumulative response rate of 94% 4.
• A study published in 2006 found that doxycycline was effective in treating syphilis, with a serological cure rate of 100% 5.
• A study published in 2010 found that azithromycin was equivalent to benzathine penicillin G in treating syphilis, with a serological cure rate of 77.6% 6.
• A study published in 2005 found that single-dose azithromycin was effective in treating syphilis, with a cure rate of 97.7% 7.
• A study published in 2012 found that ceftriaxone and doxycycline were effective in treating syphilis, particularly in patients with HIV infection 8.

Considerations for Treatment

When choosing a treatment option, considerations should include:

• Patient allergy history: Patients who are allergic to penicillin may require alternative treatments such as azithromycin or doxycycline.
• HIV status: Patients with HIV infection may require alternative treatments such as ceftriaxone or doxycycline.
• Pregnancy status: Pregnant patients should be treated with benzathine penicillin G, as it is the recommended treatment for syphilis in pregnancy.
• Resistance patterns: The emergence of antibiotic-resistant strains of Treponema pallidum should be considered when choosing a treatment option 7.