What is the recommended treatment and counseling approach for syphilis in patients?

Syphilis Treatment and Management for Pharmacists: A Comprehensive Guide

Penicillin G remains the gold standard treatment for all stages of syphilis, with specific regimens tailored to disease stage, and doxycycline as the preferred alternative for penicillin-allergic patients. 1

Disease Overview and Staging

Syphilis is a sexually transmitted infection caused by Treponema pallidum that progresses through distinct stages if left untreated:

• Primary syphilis: Characterized by a painless ulcer (chancre) at infection site
• Secondary syphilis: Manifests with widespread rash, mucocutaneous lesions, and lymphadenopathy
• Latent syphilis: Asymptomatic period with positive serology
  • Early latent: Acquired within preceding year
  • Late latent: Acquired >1 year ago or unknown duration
• Tertiary syphilis: Includes gummatous disease, cardiovascular syphilis
• Neurosyphilis: CNS involvement possible during any stage

Treatment Recommendations by Stage

Primary, Secondary, and Early Latent Syphilis

First-line treatment:

• Benzathine penicillin G 2.4 million units IM in a single dose 2, 1

Alternative regimens (for penicillin-allergic, non-pregnant patients):

• Doxycycline 100 mg orally twice daily for 14 days 2, 3
• Tetracycline 500 mg orally four times daily for 14 days 2

Late Latent Syphilis or Latent Syphilis of Unknown Duration

First-line treatment:

• Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 2, 1

Alternative regimens (for penicillin-allergic, non-pregnant patients):

• Doxycycline 100 mg orally twice daily for 28 days 2
• Tetracycline 500 mg orally four times daily for 28 days 2

Tertiary Syphilis

Recommended treatment:

• Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 2, 1
• CSF examination should be performed before initiating therapy 2

Neurosyphilis

First-line treatment:

• Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days 2, 1

Alternative regimen:

• Procaine penicillin 2.4 million units IM once daily PLUS
• Probenecid 500 mg orally four times a day, both for 10–14 days 2

Special Populations

HIV-Infected Patients

• Management is similar to HIV-negative patients, but closer follow-up is recommended 2
• For early syphilis: Benzathine penicillin G 2.4 million units IM in a single dose 2
• For late latent syphilis: Three weekly IM injections of 2.4 million units benzathine penicillin G 2
• CSF examination is recommended if neurological symptoms are present 2

Pregnant Women

• Penicillin is the only proven effective treatment during pregnancy 2
• For penicillin-allergic pregnant women, desensitization is required 2
• Some experts recommend an additional dose of benzathine penicillin 2.4 million units IM one week after the initial dose for pregnant women in the third trimester 1

Patient Counseling Points for Pharmacists

1. Jarisch-Herxheimer reaction: Advise patients about this potential reaction within 24 hours of treatment, characterized by fever, headache, and myalgia 2

2. Sexual partners: Counsel patients that:

   • Partners exposed within 90 days of diagnosis should be treated presumptively 2
   • Partners exposed >90 days before diagnosis should be treated if serologic test results are not immediately available 2

3. Follow-up testing:

   • Quantitative nontreponemal tests should be repeated at 3,6,9,12, and 24 months after treatment 1
   • Treatment success is indicated by a fourfold decrease in titers within 6 months (primary/secondary) or 12-24 months (latent) 1

4. HIV testing: All patients with syphilis should be tested for HIV due to high co-infection rates 2, 1

5. Medication adherence:

   • For doxycycline: Take with food if GI irritation occurs; absorption not markedly influenced by food 3
   • For penicillin injections: Complete the full course of treatment, especially for late syphilis 4

6. Prevention: Discuss safer sex practices, including consistent and correct condom use 1

Treatment Failure Considerations

Treatment failure or reinfection should be suspected if:

• Clinical signs or symptoms persist or recur
• Sustained fourfold increase in nontreponemal test titer occurs
• Initial high titer (≥1:32) fails to decline fourfold within 12-24 months 2, 1

Re-treatment consists of three weekly injections of benzathine penicillin G 2.4 million units IM, unless neurosyphilis is suspected 1

Common Pitfalls to Avoid

1. Inadequate follow-up: Ensure patients understand the importance of completing all follow-up serologic testing

2. Improper treatment of pregnant women: Never use alternatives to penicillin; desensitization is required for penicillin-allergic pregnant women 2

3. Missing neurosyphilis: Consider CSF examination in patients with neurologic, ophthalmic, or auditory symptoms 2

4. Incomplete partner notification: Emphasize the importance of partner treatment to prevent reinfection 2

5. Inadequate treatment of late syphilis: Do not confuse treatment regimens for early versus late syphilis; late syphilis requires 3 weekly doses of benzathine penicillin G 2, 1

6. Overlooking drug interactions: Bacteriostatic antibiotics may antagonize the bactericidal effect of penicillin 4