A randomized clinical trial found that a single intramuscular dose of benzathine penicillin G was noninferior to three weekly doses in patients with early syphilis at 6 months. Serologic response occurred in 76% of patients who received one dose and 70% of those who received three doses. No clinical relapses were observed during follow-up, and responses were similar across HIV status and across stages of disease. Among patients reassessed within 6 to 24 days following enrollment, 72% had complete symptom resolution after the initial injection.
The trial enrolled 249 patients with early syphilis at 10 US sites between October 2018 and March 2022. Patients were randomized in a 1:1 ratio to receive one or three weekly doses of benzathine penicillin G (2.4 million units each). Follow-up visits were scheduled at 1 and 2 weeks and at months 1, 3, 6, and 12, with repeat rapid plasma reagin testing at each visit. Of the patients, 97% were men, 62% were Black, and 61% were living with HIV. At enrollment, 19% had primary syphilis, 47% had secondary syphilis, and 33% had early latent syphilis.
Adverse events were frequent with injection-site pain was the most frequently reported event, affecting 76% of patients in the one-dose group and 85% in the three-dose group. Local tenderness, redness, or swelling occurred in 81% overall. Three serious adverse events were reported, none attributed to treatment. One patient developed facial paralysis from neurosyphilis, which resolved after treatment.
The trial faced limitations. Enrollment ended early due to the COVID-19 pandemic, and only 199 patients were evaluable for the primary outcome at 6 months. Exclusions were due to missed visits, incomplete regimens, receipt of other antibiotics active against Treponema pallidum, or new HIV infections. The authors also noted inconsistency between the overall results, which reported no treatment failures, and stage-specific analyses, which listed treatment failures.
The findings support one dose of benzathine penicillin G as effective as three doses for early syphilis, with similar outcomes across HIV status and disease stage."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." concluded Edward W. Hook III, MD, of the University of Alabama at Birmingham, and colleagues
Full disclosures can be found in the study.
