What is the recommended treatment for a patient diagnosed with syphilis?

What to Expect with a Diagnosis of Syphilis

If you are diagnosed with syphilis, expect to receive benzathine penicillin G as a single intramuscular injection of 2.4 million units for early-stage disease, or three weekly injections for late-stage disease, followed by mandatory HIV testing and serial blood tests to monitor treatment response. 1, 2

Immediate Steps After Diagnosis

HIV Testing is Mandatory

• All patients diagnosed with syphilis must be tested for HIV infection at the time of diagnosis 1, 2
• In high HIV prevalence areas, patients with primary syphilis should be retested for HIV after 3 months 3

Stage-Specific Treatment You Will Receive

For Primary and Secondary Syphilis (Early Stage):

• You will receive a single intramuscular injection of benzathine penicillin G 2.4 million units 3, 1
• This is the gold standard treatment backed by 50 years of clinical experience 3

For Late Latent or Unknown Duration Syphilis:

• You will receive three weekly injections of benzathine penicillin G 2.4 million units each (total 7.2 million units) 3, 1, 2

For Neurosyphilis (if CNS involvement is detected):

• You will require hospitalization for intravenous aqueous crystalline penicillin G 18-24 million units daily for 10-14 days 1, 2

What Happens If You're Allergic to Penicillin

Non-Pregnant Patients

• For early syphilis: doxycycline 100 mg orally twice daily for 14 days 1, 2
• For late latent syphilis: doxycycline 100 mg orally twice daily for 28 days 1, 2
• Critical caveat: Non-penicillin therapy for latent syphilis should only be used after a spinal tap (CSF examination) has excluded neurosyphilis 3

Pregnant Patients

• There are no exceptions—you must receive penicillin 1, 2
• If you report penicillin allergy, you will undergo desensitization followed by penicillin treatment 3, 1, 2
• Penicillin is the only therapy proven to prevent transmission to your baby and treat fetal infection 1

Expected Side Effects: The Jarisch-Herxheimer Reaction

• Within the first 24 hours after treatment, you may experience an acute febrile reaction with fever, headache, muscle aches, and other flu-like symptoms 3, 1, 2
• This reaction is especially common in early syphilis and does not indicate treatment failure 3
• Antipyretics (fever reducers) may help, but there is no proven method to prevent this reaction 3
• For pregnant women: This reaction may trigger premature labor or fetal distress, but this concern should not delay treatment 3, 1
• If pregnant and treated in the second half of pregnancy, seek immediate medical attention if you notice contractions or changes in fetal movements 1

Follow-Up Blood Tests You Will Need

For Early Syphilis (Primary, Secondary, or Early Latent)

• Quantitative nontreponemal tests (RPR or VDRL) at 6 and 12 months after treatment 1, 2
• Your blood test titers should decline fourfold (drop by two dilutions) within 6 months 1, 2

For Late Latent Syphilis

• Repeat quantitative nontreponemal tests at 6,12, and 24 months 1
• Titers should decline fourfold within 12-24 months 1

Signs of Treatment Failure

You will need re-evaluation and possible re-treatment if: 1

• Persistent or recurring signs/symptoms develop
• Titers increase fourfold (rise by two dilutions)
• Initially high titers (≥1:32) fail to decline fourfold within the expected timeframe

Important: If treatment failure is suspected, you should be re-evaluated for HIV and may need a spinal tap to check for neurosyphilis 1

Your Sexual Partners Must Be Evaluated

Partners Exposed Within 90 Days

• They should receive presumptive treatment with benzathine penicillin G 2.4 million units IM even if their blood tests are negative 3, 1, 2

Time Periods for Partner Notification

• Primary syphilis: 3 months plus duration of your symptoms 3
• Secondary syphilis: 6 months plus duration of your symptoms 3
• Early latent syphilis: 1 year 3

Special Considerations Based on Your Situation

If You Have HIV

• You will receive the same penicillin regimens as HIV-negative patients 1, 2
• You may have atypical blood test responses but generally respond well to standard treatment 1
• You will need closer follow-up to detect potential treatment failure 1

If You Are Pregnant

• You will be screened for syphilis at your first prenatal visit, during the third trimester, and at delivery 1, 2
• Some experts recommend a second dose of benzathine penicillin 2.4 million units IM one week after the initial dose for primary, secondary, or early latent syphilis during pregnancy 1
• Never accept alternatives to penicillin—they do not reliably cure fetal infection 1

If You Have Neurological or Eye Symptoms

• You will need a spinal tap (CSF examination) before treatment 3, 1
• Eye involvement (uveitis, vision changes) is frequently associated with neurosyphilis and requires neurosyphilis treatment regimens 3

Critical Pitfalls to Avoid

• Do not accept oral penicillin preparations—they are ineffective for syphilis 1
• Do not switch between different blood test methods (RPR vs VDRL) during monitoring—results cannot be directly compared 1
• Do not rely on treponemal antibody tests (like FTA-ABS) to monitor treatment response—they remain positive for life and do not correlate with disease activity 1
• If you miss a weekly penicillin dose for late syphilis, an interval of 10-14 days between doses may be acceptable before restarting, but this is NOT acceptable for pregnant women 1, 4

Current Treatment Challenges

• There is an ongoing shortage of benzathine penicillin G in some areas 5
• If BPG is unavailable, doxycycline can be used as a temporary alternative for non-pregnant patients with early syphilis, but efforts should continue to locate BPG 5
• Azithromycin should NOT be used in the United States due to widespread resistance and documented treatment failures 1