A 28-year-old man presents with a painless ulcer on the glans penis for 3 weeks, with regional lymphadenopathy. Dark-field microscopy confirms Treponema pallidum. What is the drug of choice for treatment of primary syphilis?

Explanation

## Drug of Choice for Primary Syphilis **Key Point:** Benzathine penicillin G is the gold standard first-line treatment for all stages of syphilis, including primary syphilis. ### Mechanism & Rationale 1. **Beta-lactam antibiotic** — bactericidal; inhibits cell wall synthesis of T. pallidum 2. **Long-acting formulation** — achieves sustained treponemicidal levels for ≥3 weeks 3. **Excellent CNS penetration** — prevents neurosyphilis relapse 4. **Proven efficacy** — >95% cure rate in primary syphilis when given early ### Dosing Regimen for Primary Syphilis - **Benzathine penicillin G 2.4 million units IM as a single dose** - Administered as a single intramuscular injection - Provides adequate serum and CSF levels for ≥3 weeks ### Alternative Regimens (for penicillin allergy) | Allergy Status | First-line Alternative | Dosing | |---|---|---| | Non-pregnant, non-CNS | Doxycycline | 100 mg PO BID × 28 days | | Non-pregnant, non-CNS | Ceftriaxone | 1 g IM/IV daily × 10–14 days | | Pregnant | Penicillin (desensitization required) | — | | Penicillin allergy + pregnancy | Ceftriaxone | 1 g IM/IV daily × 10–14 days | **High-Yield:** Benzathine penicillin G is the ONLY agent recommended in pregnancy for any stage of syphilis. Desensitization is mandatory if patient has true IgE-mediated allergy. **Clinical Pearl:** Jarisch-Herxheimer reaction (fever, myalgia, rash) may occur within 24 hours of first dose due to release of treponemal antigens; pretreat with acetaminophen and counsel patient. **Mnemonic:** **PENICILLIN = Primary, Early, Neurosyphilis, Congenital** — the drug covers all stages.