## First-Line Treatment of Primary Syphilis **Key Point:** Benzathine penicillin G remains the gold standard for all stages of syphilis, including primary, secondary, and early latent syphilis. ### Rationale for Benzathine Penicillin G **High-Yield:** Benzathine penicillin G 2.4 million units IM as a single dose is the preferred regimen because: 1. Achieves treponemicidal levels in serum and CSF 2. Provides prolonged therapeutic levels (2–3 weeks) 3. Single-dose compliance eliminates adherence issues 4. Cost-effective and widely available 5. Penicillin is bactericidal against *Treponema pallidum* ### Alternative Regimens (for Penicillin-Allergic Patients) | Stage | Penicillin-Allergic Regimen | Duration | |-------|------------------------------|----------| | Primary/Secondary | Doxycycline 100 mg PO BD | 28 days | | Primary/Secondary | Ceftriaxone 1 g IM/IV daily | 10–14 days | | Neurosyphilis | Ceftriaxone 2 g IV 12-hourly | 10–14 days | | Neurosyphilis | Penicillin G IV (if allergy ruled out) | 10–14 days | **Clinical Pearl:** Doxycycline is a reasonable alternative in non-pregnant, penicillin-allergic patients, but requires 28 days of oral therapy — lower compliance than single-dose IM penicillin. **Warning:** Azithromycin resistance in *T. pallidum* is now widespread (>50% in many regions); it is no longer recommended as first-line or alternative therapy. ### Jarisch-Herxheimer Reaction **Key Point:** Expect fever, chills, and malaise 6–12 hours after first penicillin dose due to endotoxin release from dying spirochaetes. Pretreat with NSAIDs or acetaminophen; reaction is self-limited and not a reason to stop therapy.
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