From the Guidelines
For patients with a penicillin allergy, doxycycline 100 mg orally twice daily for 14 days is the recommended alternative treatment for syphilis. This recommendation is based on the limited data available for alternative treatments in penicillin-allergic patients, as outlined in the 2010 sexually transmitted diseases treatment guidelines 1. The choice of doxycycline over other alternatives such as tetracycline or ceftriaxone is due to its better compliance rate and fewer gastrointestinal side effects. Some key points to consider when treating syphilis in patients with a penicillin allergy include:
- Doxycycline is the preferred alternative treatment due to its efficacy and better patient compliance compared to tetracycline 1.
- Tetracycline 500 mg four times daily for 14 days can be used as an alternative, but it may cause more gastrointestinal side effects, leading to poorer compliance 1.
- Ceftriaxone 1 g daily either IM or IV for 10–14 days may be effective, but the optimal dose and duration have not been defined, and cross-reactivity with penicillin may occur in some patients 1.
- Azithromycin as a single 2-g oral dose should be used with caution due to the risk of resistance and treatment failures, especially in certain geographical areas and populations such as MSM or pregnant women 1. It is essential to monitor patients receiving alternative therapies closely, with follow-up serologic testing at 6 and 12 months after treatment to ensure an adequate response. In cases where compliance or follow-up cannot be ensured, penicillin desensitization followed by treatment with benzathine penicillin may be necessary 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 treatment for syphilis in patients with a penicillin allergy is doxycycline 100 mg, by mouth, twice a day for:
- 2 weeks for early syphilis
- 4 weeks for syphilis of more than one year’s duration 2
From the Research
Treatment Options for Syphilis in Patients with Penicillin Allergy
- In patients with a penicillin allergy, alternative treatments for syphilis include tetracyclines, erythromycin, and thiamphenicol 3
- Doxycycline is a preferred treatment option, with a recommended dosage of 100 mg twice daily for 12 days 3
- Ceftriaxone is also considered an effective alternative to penicillin, with similar serological response rates and treatment failure rates 4, 5
- Other treatment options include azithromycin, but its efficacy is not as well established as doxycycline or ceftriaxone 6
Comparison of Treatment Efficacy
- Studies have shown that doxycycline and ceftriaxone have similar efficacy to penicillin in treating early syphilis 4, 5
- A systematic review and network meta-analysis found that ceftriaxone was as effective as penicillin in treating early syphilis, with a higher serological response rate at 6-month follow-up 5
- Another study found that doxycycline and benzathine penicillin had similar serological response rates in HIV-infected patients with early syphilis 7
Considerations for Treatment
- Treatment with semisynthetic penicillins or cephalosporins should not be attempted in patients with a penicillin allergy due to possible cross-sensitivity 3
- Desensitization is required for patients with a penicillin allergy who are pregnant or have neurosyphilis 6
- The choice of treatment should be based on the patient's specific needs and medical history, as well as the severity and stage of the disease 6, 4, 5