## Drug of Choice for Tertiary Syphilis (Cardiovascular) **Key Point:** Benzathine penicillin G 2.4 million units IM weekly for 3 weeks is the standard first-line treatment for tertiary syphilis, including cardiovascular, gummatous, and late neurosyphilis. ### Rationale for Extended Regimen in Tertiary Disease 1. **Longer duration of therapy** — tertiary syphilis involves chronic tissue inflammation and fibrosis; 3 weekly doses ensure sustained bactericidal levels 2. **Adequate CNS penetration** — prevents progression to general paresis of the insane (GPI) or tabes dorsalis 3. **Proven efficacy** — halts progression and prevents complications (aortic rupture, cardiac death) 4. **Cost-effective** — outpatient IM administration vs. prolonged IV therapy ### Treatment Regimens by Syphilis Stage | Stage | Duration | Regimen | |---|---|---| | **Primary** | Single dose | Benzathine PCN G 2.4 MU IM × 1 | | **Secondary** | 3 weeks | Benzathine PCN G 2.4 MU IM weekly × 3 | | **Tertiary (non-neuro)** | 3 weeks | Benzathine PCN G 2.4 MU IM weekly × 3 | | **Tertiary (neurosyphilis/GPI)** | 10–14 days | Aqueous crystalline PCN G 18–24 MU IV daily | | **Congenital** | 10 days | Aqueous crystalline PCN G 50,000 U/kg IV Q4–6H | **High-Yield:** The distinction is critical: **cardiovascular/gummatous tertiary syphilis** → benzathine (IM, weekly × 3); **neurosyphilis** → aqueous crystalline (IV, daily × 10–14 days). **Clinical Pearl:** Cardiovascular syphilis (aortitis, aortic regurgitation, coronary ostial stenosis) is irreversible once established; treatment prevents further deterioration but does not reverse valve damage. Surgical intervention may be needed if severe AR develops. **Mnemonic:** **3-WEEK RULE for Tertiary** — benzathine penicillin G 2.4 MU IM weekly for 3 weeks covers all tertiary non-neurological forms.
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