What is the appropriate treatment for syphilis in a patient with rising titers from 1:16 to 1:64 after initial treatment with Doxycycline (doxycycline) in November 2024, who is allergic to Penicillin (penicillin)?

From the Guidelines

For a patient with syphilis showing rising titers from 1:16 to 1:64 after doxycycline treatment and who has a penicillin allergy, I recommend treatment with ceftriaxone 1-2 g intravenously or intramuscularly daily for 10-14 days, as this regimen has been shown to be effective in treating early syphilis, especially in patients who cannot tolerate penicillin 1. This recommendation is based on the most recent and highest quality study available, which suggests that ceftriaxone is a reasonable treatment for early syphilis, with comparable efficacy to benzathine penicillin G 1.

Key Considerations

• The rising titers indicate treatment failure with the previous doxycycline regimen, requiring prompt retreatment.
• Before starting ceftriaxone, it is essential to confirm that there is no cross-reactivity with the penicillin allergy.
• For patients with severe penicillin allergy who cannot tolerate cephalosporins, consider penicillin desensitization followed by appropriate penicillin therapy, especially if the infection is neurosyphilis or late-stage syphilis.
• Follow-up serologic testing should be performed at 3,6, and 12 months after treatment to ensure an appropriate response, indicated by a fourfold decrease in titers.

Alternative Treatment Options

• Doxycycline 100 mg orally twice daily for 28 days could be considered as an alternative treatment option, especially if the patient has previously responded to doxycycline treatment 1.
• However, the rising titers in this patient suggest treatment failure with the previous doxycycline regimen, making ceftriaxone a more suitable option.

Important Notes

• Azithromycin should not be used as a treatment option due to concerns regarding macrolide resistance 1.
• Penicillin desensitization followed by appropriate penicillin therapy may be considered in patients with severe penicillin allergy who cannot tolerate cephalosporins 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 patient has rising titers after initial treatment with doxycycline, indicating treatment failure. Since the patient is allergic to penicillin, the appropriate treatment would be to extend the course of doxycycline.

• The patient should be treated with doxycycline 100 mg, by mouth, twice a day for an extended period, likely 4 weeks, as the initial 2-week course was not sufficient 2.

From the Research

Treatment Options for Syphilis

• The patient has rising titers from 1:16 to 1:64 after initial treatment with Doxycycline, indicating a potential treatment failure 3, 4.
• Given the patient's allergy to Penicillin, alternative treatment options need to be considered.
• Azithromycin has been shown to be a promising alternative to Penicillin for the treatment of syphilis, with a cumulative response rate of 94% in one study 5.
• Doxycycline is also an effective second-line treatment for early syphilis, with similar serological treatment success rates compared to Penicillin 3, 4.

Considerations for Treatment

• The patient's rising titers indicate a need for re-treatment or alternative treatment options.
• Azithromycin or an alternative regimen such as Ceftriaxone could be considered as treatment options 6.
• It is essential to monitor the patient's serological response to treatment and adjust the treatment plan as needed 6, 7.
• The use of Doxycycline in combination with other antibiotics, such as Benzathine Penicillin G, may also be considered to improve treatment outcomes 7.