The key treatment for syphilis is Penicillin, specifically intramuscular benzathine penicillin G. Penicillin is highly effective because it eradicates the causative organism, Treponema pallidum, by inhibiting bacterial cell wall synthesis. It is the preferred treatment due to its excellent efficacy, safety profile, and ability to prevent progression to late-stage disease. Alternative antibiotics are considered only in cases of penicillin allergy. Prompt administration can prevent serious complications and transmission.

Reference: Harrison's Principles of Internal Medicine, J. Larry Jameson, 20th Edition.