Prolonged Benzathine Penicillin G Improves Long-term Serological Outcomes in HIV-negative Neurosyphilis.

BACKGROUND: Neurosyphilis is a serious complication of Treponema pallidum infection. Some patients experience relapse or serofast response despite standard intravenous penicillin G. While adjunctive benzathine penicillin is recommended in some guidelines, its optimal duration and effectiveness remain unclear. This study aimed to identify predictors of serological response and evaluate the effect of prolonged therapy in HIV-negative neurosyphilis. METHODS: We retrospectively analyzed 246 HIV-negative neurosyphilis patients treated at three hospitals from 2011 to 2024. Patients received either standard therapy (14-day intravenous penicillin G plus 3 weekly benzathine penicillin injections) or prolonged therapy (benzathine penicillin ≥ 4 weeks). Serological cure was defined as a ≥ 4-fold decline or reversion to negative in TRUST/RPR titers. RESULT: At 6 and 12 months, cure rates were higher in the prolonged group (35.9% and 62.0%) than in the standard group (17.5% and 20.1%) (both P < 0.001). Multivariable analysis showed that headache predicted better response, while alcohol use and cerebral infarction were associated with poor outcomes. Prolonged therapy independently predicted 12-month cure (OR = 8.707, P < 0.001). CONCLUSIONS: Prolonged benzathine penicillin improves long-term serological outcomes and supports a staged treatment approach in HIV-negative neurosyphilis.