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One Dose of Benzathine Penicillin G Noninferior to Three Doses for Syphilis

Medically reviewed by Carmen Pope, BPharm. Last updated on Sep 4, 2025.

via HealthDay

THURSDAY, Sept. 4, 2025 -- For patients with early syphilis, treatment with one dose of 2.4 million units of benzathine penicillin G is noninferior to treatment with three doses, according to a study published in the Sept. 4 issue of the New England Journal of Medicine.

Edward W. Hook III, M.D., from the University of Alabama at Birmingham, and colleagues conducted a noninferiority trial involving 249 persons with early syphilis, with or without HIV infection, who were randomly assigned to receive intramuscular injections of benzathine penicillin G in a one-time dose of 2.4 million units or three doses of 2.4 million units administered at weekly intervals. Seroreversion to nonreactive status or a decrease in the rapid plasma reagin titer by two or more dilutions at six months (serologic response) was the primary end point.

The researchers found that in the single-dose group and three-dose group, 76 and 70 percent of patients, respectively, had a serologic response at six months (difference, −9 percentage points; 90 percent confidence interval, −15 to 3, indicating noninferiority). Neither group had clinical relapse or treatment failure. A serologic response at six months was seen in 76 and 76 percent of those with and without HIV infection, respectively, in the one-dose group, and in 71 and 70 percent, respectively, in the three-dose group.

"The elimination of unnecessary doses of benzathine penicillin G reduces the cost of treatment, aligns with the principles of antimicrobial stewardship, and is more convenient for patients in that the numbers of clinic visits and painful intramuscular injections are decreased," the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

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