First-line treatment for early syphilis is?

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The main idea is that early syphilis is best treated with a single, depot-forming antibiotic that gives sustained penicillin levels. The recommended first-line therapy is benzathine penicillin G 2.4 million units given by intramuscular injection as a single dose. This formulation releases penicillin slowly, maintaining effective levels to eradicate Treponema pallidum in primary, secondary, and early latent syphilis, offering high cure rates with convenient dosing.

Alternative regimens exist for specific situations, but they’re not as optimal as the single-dose penicillin approach. Doxycycline or tetracycline can be used in nonpregnant patients with penicillin allergy, but require longer courses and may have less robust evidence for efficacy. Azithromycin has shown resistance in T. pallidum and is not recommended. In pregnancy, penicillin remains the drug of choice, with desensitization advised if the patient has a true penicillin allergy.