Can we start treatment with penicillin (or alternative antibiotics if allergic) for a patient with a positive VDRL result indicating syphilis?

Piperacillin-Tazobactam is NOT Appropriate for VDRL-Positive Syphilis

No, you cannot start piperacillin-tazobactam (piptaz) for treatment of syphilis—penicillin G (benzathine or aqueous crystalline) is the only FDA-approved and guideline-recommended treatment for all stages of syphilis. 1, 2

Why Piptaz is Inappropriate

• Piperacillin-tazobactam has no established role in syphilis treatment and is not mentioned in any CDC guidelines, FDA labeling for syphilis, or clinical evidence for treating Treponema pallidum 1, 3
• Penicillin G remains the only drug with documented efficacy for treating syphilis across all stages, including preventing maternal-fetal transmission 1, 3
• The FDA specifically indicates penicillin G for syphilis (congenital and neurosyphilis) caused by Treponema pallidum, with no alternative beta-lactam antibiotics approved 2

Correct Treatment Algorithm Based on Stage

Step 1: Confirm Diagnosis and Stage

• Obtain quantitative nontreponemal test (VDRL or RPR) to establish baseline titer 1, 4
• Confirm with treponemal test (FTA-ABS or TP-PA) to rule out false-positive VDRL 4, 3
• Determine stage: primary, secondary, early latent (<1 year), late latent (>1 year), or tertiary 1
• Test for HIV in all patients with syphilis, as coinfection affects monitoring 1, 4

Step 2: Evaluate for Neurosyphilis

Perform lumbar puncture for CSF examination if any of the following are present 1, 4:

• Neurologic signs/symptoms (cranial nerve palsies, altered mental status)
• Ocular manifestations (uveitis, optic neuritis)
• Tertiary syphilis
• Treatment failure (persistent/rising titers)
• HIV infection with late latent syphilis or RPR ≥1:32

Step 3: Administer Appropriate Penicillin Regimen

For Primary, Secondary, or Early Latent Syphilis:

• Benzathine penicillin G 2.4 million units IM as a single dose 1, 3, 2
• This is the definitive treatment with decades of proven efficacy 5, 6

For Late Latent Syphilis or Latent of Unknown Duration:

• Benzathine penicillin G 7.2 million units total: three doses of 2.4 million units IM at weekly intervals 1, 3

For Neurosyphilis:

• Aqueous crystalline penicillin G 18-24 million units IV daily (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days 7, 1
• Some experts add a single dose of benzathine penicillin G 2.4 million units IM after completing IV therapy to ensure adequate total duration 7

Step 4: Manage Penicillin Allergy (If Present)

For Non-Pregnant Adults with Early Syphilis:

• Doxycycline 100 mg orally twice daily for 14 days is the preferred alternative 1, 3, 8
• Tetracycline 500 mg orally four times daily for 14 days is another option 1

For Late Latent Syphilis in Non-Pregnant Adults:

• Doxycycline 100 mg orally twice daily for 28 days 1, 8

For Pregnant Women or Neurosyphilis:

• Penicillin desensitization is MANDATORY—no exceptions 1, 3
• Penicillin is the only therapy proven to prevent maternal-fetal transmission and treat fetal infection 1, 3
• Alternatives like doxycycline, erythromycin, azithromycin, and ceftriaxone are inadequate in pregnancy 1

Ceftriaxone Considerations:

• Ceftriaxone 1 gram IM/IV daily for 10-14 days may be considered for early syphilis in penicillin-allergic non-pregnant adults, though data are limited 1
• For neurosyphilis, ceftriaxone 2 grams IV daily for 10-14 days has minimal supporting evidence 1
• Do NOT use azithromycin due to widespread macrolide resistance and documented treatment failures in the United States 1, 3

Step 5: Follow-Up Monitoring

• Perform quantitative nontreponemal tests (same method, same laboratory) at 6 and 12 months for primary/secondary syphilis 1, 4
• For latent syphilis, repeat testing at 6,12, and 24 months 1
• Treatment success = fourfold decline in titer within 6 months for early syphilis or 12-24 months for late syphilis 1, 4, 6
• HIV-positive patients require more frequent monitoring at 3-month intervals 4

Critical Pitfalls to Avoid

• Never use oral penicillin preparations—they are ineffective for syphilis 1, 3
• Do not monitor treatment response with treponemal tests—these remain positive for life regardless of cure 7, 1, 3
• Do not switch between VDRL and RPR during follow-up—results cannot be directly compared 1, 3
• Do not assume treatment failure with persistent low titers (<1:8)—15-25% of patients remain "serofast" despite adequate treatment 1
• Warn patients about Jarisch-Herxheimer reaction—acute febrile reaction within 24 hours of treatment is common in early syphilis and does not indicate treatment failure 1, 4

Partner Management

• Evaluate and treat all sexual contacts within 90 days for primary syphilis presumptively, even if seronegative 1, 4
• For secondary syphilis, extend to 6 months plus duration of symptoms 1
• For early latent syphilis, extend to 1 year 1