Ceftriaxone compared with penicillin G for the treatment of neurosyphilis: study protocol for a multicenter randomized controlled trial

Abstract

Background Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. Methods/design In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. Discussion This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. Trial registration Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.

Case report—Depression with psychotic features as an atypical presentation of neurosyphilis

“… 9 Because of the patient's delusion of poisoning and suspicion toward the medical staff, we treated him with a single dose of ceftriaxone instead of five doses of penicillin daily, as a recent study has shown no difference between both regimens in the treatment of neurosyphilis in psychiatric patients. 10 In this case, it is difficult to classify the syphilis stage as the history is not specific enough. As symptoms began approximately 9 years ago, we assumed a late‐stage neurosyphilis.…”

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis

“… 70 , 71 Several trials are currently underway to document efficacy of cephalosporins for different stages of syphilis. 72 , 73 In case of neurosyphilis, based on observational studies, ceftriaxone or the combination of procaine penicillin G with probenecid are the main alternative therapeutic options. 74 , 75 Recent observational data suggest similar efficacy in neurosyphilis between ceftriaxone and intravenous penicillin G, although there is much less experience with the former.…”

Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention

“…In treatment of neurosyphilis, it is crucial to consider the BBB penetration and effective drug concentrations in CSF ( 120 ). The recommended treatment for neurosyphilis is intravenous aqueous crystalline penicillin G (18–24 million units per day, continuous infusion for 10–14 days) ( 14 ).…”