Introduction The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin in non-pregnant, immunocompetent adults with early syphilis since there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an HIV co-infection.

Methods A randomised, open-label controlled study evaluating the efficacy of ceftriaxone and benzathine penicillin was performed in four hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, intravenously, once daily for 10 days) or benzathine penicillin (2.4 million units, intramuscularly, once per week for two weeks). Serological response was defined as at least a 4-fold decline in rapid plasma regain(RPR) titer.

Results In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The median follow-up period was 9 months. Among these 230 patients, a serological response was observed in 83.9% and 86.5% at the 6- and 12 month follow-ups, respectively. There were significant differences between the ceftriaxone- and penicillin-treated groups at both the 6- (90.2% vs 80.0%; p=0.012) and 12 month follow-ups (92.0% vs 81.4%; p=0.021), especially in patients with secondary syphilis (p<0.05). Moreover, the Jarisch–Herzheimer reaction was positively associated with treatment regimen prognosis (p<0.05).

Conclusion Our serological data demonstrate that this ceftriaxone regimen is more effective than the currently recommended benzathine penicillin regimen for early syphilis in non-pregnant, immunocompetent patients, especially for secondary syphilis.