From the Guidelines
For patients who cannot use penicillin to treat syphilis, the recommended oral alternative is doxycycline, as it is an acceptable option if penicillin cannot be used, according to the 2022 study published in Clinical Infectious Diseases 1. The dosage and duration of doxycycline treatment may vary depending on the stage of syphilis.
- For early latent syphilis, doxycycline can be used as an alternative to penicillin, as stated in the study 1.
- The study does not specify the exact dosage and duration of doxycycline treatment, but based on general medical knowledge, doxycycline 100 mg taken twice daily for 14 days is a common regimen for primary, secondary, or early latent syphilis, and for 28 days for late latent syphilis or syphilis of unknown duration. Key points to consider when using doxycycline as an alternative to penicillin include:
- Doxycycline is generally considered less effective than penicillin, which remains the gold standard for treating syphilis.
- Patients should be monitored with follow-up serologic testing at 6 and 12 months after treatment to ensure adequate response.
- Sexual partners should also be evaluated and treated if necessary, and patients should abstain from sexual contact until treatment is complete and lesions have healed. It is essential to note that while doxycycline is an acceptable alternative, penicillin remains the preferred treatment for syphilis, and doxycycline should only be used when penicillin cannot be used, as stated in the study 1.
From the FDA Drug Label
Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.
The recommended oral regimen for treating syphilis when penicillin cannot be used is doxycycline 100 mg, twice a day.
- For early syphilis, the treatment duration is 2 weeks.
- For syphilis of more than one year’s duration, the treatment duration is 4 weeks 2.
From the Research
Oral Regimen for Syphilis
When penicillin cannot be used, the recommended oral regimen for treating syphilis includes:
- Doxycycline, which is the preferred second-line agent for the treatment of syphilis 3, 4, 5, 6
- Azithromycin, which has shown promise as an alternative to benzathine penicillin G for syphilis treatment 7
Dosage and Duration
The dosage and duration of the oral regimen may vary depending on the stage of syphilis and the patient's condition:
- Doxycycline: 100 mg orally, twice daily for 14 days for early syphilis 3, 4, 5, and a 28-day course for infections older than 1 year or undetermined 6
- Azithromycin: a single 2.0-g dose or two 2.0-g doses given 1 week apart 7
Efficacy
The efficacy of the oral regimen for syphilis has been studied in several trials:
- Doxycycline has been shown to be effective in treating early syphilis, with a serological success rate similar to that of benzathine penicillin G 3, 4, 5
- Azithromycin has been shown to be a promising alternative to benzathine penicillin G for syphilis treatment, with a cumulative response rate of 94% for a single 2.0-g dose and 83% for two 2.0-g doses given 1 week apart 7
- However, doxycycline may have a reduced success rate in attaining resolution in late and undetermined syphilis infection 6