Comparable treatment response rates with benzathine penicillin and doxycycline in early syphilis: evidence from a large German cohort.

PURPOSE: This study aimed to identify predictors of serological nonresponse, defined as a less than fourfold decline in VDRL titers at 12 months, and factors associated with higher minimum titers during months 13-24 after treatment, and to assess whether either outcome was associated with the antibiotic regimen. METHODS: We conducted a retrospective longitudinal cohort study of individuals with early syphilis treated with benzathine penicillin G or doxycycline and followed for 24 months. Predictors of 12-month serological response were assessed using multivariable logistic regression. Factors associated with the lowest log2-transformed VDRL titer recorded during months 13-24 were evaluated using multivariable linear regression. RESULTS: Among the 633 eligible cases, 106 (16.7%) did not achieve a fourfold decline within 12 months after treatment. In addition, 127 cases (20.1%) showed incomplete seroreversion, defined as a minimum VDRL titer of ≥ 1:2 during months 13-24. The antibiotic regimen was not associated with either outcome. Higher baseline VDRL titers were associated with greater odds of achieving a fourfold decline by 12 months, but also with higher minimum VDRL titers during months 13-24. In contrast, age > 65 years and PrEP use were associated with lower odds of achieving a fourfold decline. Several clinical and immunological characteristics were associated with the magnitude of late VDRL seroreactivity during the late follow-up period. CONCLUSIONS: Serological outcomes were associated primarily with baseline and host characteristics rather than the antibiotic regimen. Doxycycline may be an effective alternative to benzathine penicillin G for early syphilis, although the observational design does not establish equivalence.