What is the recommended treatment for primary syphilis?

Primary Syphilis Management

Recommended Treatment

Benzathine penicillin G 2.4 million units intramuscularly as a single dose is the definitive treatment for primary syphilis. 1, 2

This regimen has demonstrated 90-100% treatment success rates and represents over 50 years of clinical experience as the gold standard therapy. 3, 4

Essential Concurrent Actions

All patients diagnosed with primary syphilis must be tested for HIV infection immediately. 1, 2

• HIV coinfection affects follow-up monitoring frequency and may increase risk for neurologic complications 1, 2
• The same single-dose penicillin regimen is used regardless of HIV status 1

Alternative Treatment for Penicillin Allergy

For documented penicillin allergy in non-pregnant adults, doxycycline 100 mg orally twice daily for 14 days is the preferred alternative. 1, 2, 5

• Tetracycline 500 mg orally four times daily for 14 days is an option, but compliance is typically worse due to gastrointestinal side effects 2
• Research demonstrates that doxycycline/tetracycline achieves 100% serological treatment success rates comparable to penicillin 6
• Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment—no alternatives are acceptable 1

Follow-Up Protocol

HIV-negative patients require clinical and serologic evaluation at 6 and 12 months using quantitative nontreponemal tests (RPR or VDRL). 3, 2

• HIV-positive patients require more frequent monitoring at 3,6,9, and 12 months 2
• Treatment success is defined as a fourfold decline in nontreponemal titer within 6 months 1, 2

Treatment Failure Criteria

Treatment failure should be suspected if any of the following occur: 3, 2

• Nontreponemal titers fail to decline fourfold within 6 months after therapy
• Clinical signs or symptoms persist or recur
• Sustained fourfold increase in titer compared to baseline

When treatment failure is suspected: 7

• Re-evaluate for HIV infection 7
• Perform CSF examination to exclude neurosyphilis 3, 7
• Re-treat with benzathine penicillin G 2.4 million units IM weekly for 3 weeks if CSF is normal 7
• If CSF shows neurosyphilis, treat with aqueous crystalline penicillin G 18-24 million units daily IV for 10-14 days 7

Partner Management

All sexual contacts from the past 3 months plus duration of symptoms should be evaluated and treated presumptively, even if seronegative. 3, 1

• Partners should receive the same treatment regimen (benzathine penicillin G 2.4 million units IM single dose) 2

Critical Pitfalls to Avoid

Do not use treponemal tests (FTA-ABS, TP-PA) to monitor treatment response—they remain positive for life and do not correlate with disease activity. 1, 2

Do not switch between different nontreponemal test types (VDRL vs RPR) when monitoring—results cannot be directly compared. 1, 2

Do not assume treatment failure in patients with persistent low-titer reactivity ("serofast" state)—approximately 15-25% of patients remain serofast with low unchanging titers despite cure. 2

Do not use oral penicillin preparations—they are ineffective for syphilis treatment. 1

Jarisch-Herxheimer Reaction

Patients should be informed about the Jarisch-Herxheimer reaction, an acute febrile reaction that may occur within 24 hours after treatment. 1

• This reaction may include fever, headache, myalgia, and other flu-like symptoms 1
• It is more common in early syphilis but does not indicate treatment failure 1