## First-Line Treatment of Primary Syphilis **Key Point:** Benzathine penicillin G (BPG) is the gold-standard, first-line treatment for all stages of syphilis, including primary, secondary, and early latent syphilis. ### Dosing Regimen for Primary Syphilis - **Benzathine penicillin G:** 2.4 million units IM as a single dose (1.2 million units in each buttock) - Achieves adequate serum and CSF levels for T. pallidum eradication - Single-dose convenience ensures compliance ### Why Penicillin Remains First-Line 1. **Bactericidal activity:** Inhibits cell wall synthesis via transpeptidase inhibition 2. **Excellent tissue penetration:** Including CNS (critical for neurosyphilis) 3. **No resistance:** T. pallidum has never developed penicillin resistance in >70 years of use 4. **Cost-effective and safe:** Minimal toxicity when used appropriately ### Alternative Regimens (Penicillin-Allergic Patients) | Allergy Status | First-Line Alternative | Dosing | |---|---|---| | Non-pregnant, non-penicillin allergy | Benzathine penicillin G | 2.4 MU IM × 1 | | Pregnant (any allergy) | Penicillin desensitization + BPG | Desensitize, then BPG | | Non-pregnant, IgE-mediated allergy | Doxycycline | 100 mg PO BD × 28 days | | Non-pregnant, non-IgE allergy | Ceftriaxone | 1 g IM daily × 10 days | **High-Yield:** Doxycycline and ceftriaxone are acceptable alternatives in penicillin-allergic non-pregnant patients, but penicillin remains the standard of care when allergy history permits. **Clinical Pearl:** In pregnant women with syphilis, penicillin desensitization should be performed even in allergic patients, because doxycycline is teratogenic and ceftriaxone crosses the placenta unpredictably. **Warning:** Azithromycin is NOT recommended as first-line due to emerging resistance and treatment failures reported in several regions, including parts of Asia. [cite:Harrison 21e Ch 195]
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