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.
Treatment Regimens
For primary, secondary, or early latent syphilis (less than one year duration), a single dose of 2.4 million units of benzathine penicillin G is the standard treatment.
- This regimen is based on the latest evidence from the 2022 study published in Clinical Infectious Diseases 1.
- The study suggests that one dose of benzathine penicillin G is sufficient for early syphilis, even in HIV-infected patients. 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.
Alternative Treatments
For patients with penicillin allergy, alternatives include doxycycline (100 mg orally twice daily for 14 days) or tetracycline (500 mg orally four times daily for 14 days), though these are less effective, as noted in the 2022 study 1.
- Doxycycline or other tetracyclines can be used as acceptable alternate agents when penicillin therapy is not feasible.
- Azithromycin is not recommended due to concerns regarding macrolide resistance, as stated in the 2022 study 1.
Special Considerations
Pregnant women with penicillin allergy should undergo desensitization and receive penicillin treatment, as alternative antibiotics may not adequately treat the fetus.
- This approach is supported by the 2009 guidelines from the CDC, NIH, and HIV Medicine Association of the Infectious Diseases Society of America 1. Following treatment, patients should be monitored with blood tests to confirm the infection is resolving.
- The 2009 guidelines also recommend retreating persons with early-stage syphilis who do not experience at least a fourfold decrease in serum nontreponemal titers 6--12 months after therapy 1.
From the Research
Treatment Options for Syphilis
The recommended treatment for syphilis is primarily based on the stage of the disease. According to various studies, the following are key points to consider:
- Benzathine penicillin G is the first-line treatment for early syphilis in non-penicillin-allergic patients 2, 3, 4, 5.
- Doxycycline is considered a second-line treatment for syphilis, especially when penicillin is not feasible due to allergy or availability issues 3, 5, 6.
- Azithromycin has been studied as an alternative treatment for early syphilis, showing promising results in some trials 2, 4.
Efficacy of Treatment Options
Studies have compared the efficacy of these treatment options:
- A randomized, comparative pilot study found that azithromycin had a cumulative response rate of 94% for a single 2.0-g dose, compared to 86% for benzathine penicillin G 2.
- A study comparing doxycycline with benzathine penicillin G found that doxycycline appeared to be an effective agent for the treatment of early syphilis, with no serological failures in the doxycycline group 3.
- A phase III equivalence trial found that azithromycin at a dosage of 2.0 g administered orally was equivalent to benzathine penicillin G for the treatment of early syphilis in persons without HIV infection 4.
Challenges and Considerations
There are challenges and considerations in treating syphilis, including:
- A shortage of benzathine penicillin G, which can impact treatment availability 5.
- The need for alternative treatments, such as doxycycline, in cases where penicillin is not feasible 5, 6.
- Variations in treatment response, including the potential for serofast results in patients with latent or indeterminate syphilis treated with doxycycline 6.