Ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis in France: a retrospective multicentre study

Summary Background Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative treatment, the effectiveness of which remains unclear. We aimed to assess the effectiveness of ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis. Methods We did a retrospective multicentre study including patients with neurosyphilis who were treated at one of eight tertiary care centres in France, from Jan 1, 1997, to Dec 31, 2017. We defined neurosyphilis as positive treponemal and non-treponemal tests and at least one of otic syphilis, ocular syphilis, either neurological symptom with a positive result on cerebrospinal fluid (CSF)-VDRL or CSF-PCR tests, or more than five leukocytes in a CSF cell count. Patients with neurosyphilis were identified from the medical information department database of each centre and assigned to one of two groups on the basis of the initial treatment received (ie, benzylpenicillin group or ceftriaxone group). The primary outcome was the overall clinical response (ie, proportion of patients with a complete or partial response) 1 month after treatment initiation. The secondary endpoints were proportions of patients with a complete response at 1 month and serological response at 6 months, and length of hospital stay. Findings Of 365 patients with a coded diagnosis of neurosyphilis in one of the eight care centres during 1997-2017, 208 were included in this study (42 in the ceftriaxone group and 166 in the benzylpenicillin group). The mean age of patients was 44 center dot 4 years (SD 13 center dot 4), and 193 (93%) were men. We observed 41 instances of overall clinical response (98%) in the ceftriaxone group versus 125 (76%) in the benzylpenicillin group (crude odds ratio [OR] 13 center dot 02 [95% CI 1 center dot 73-97 center dot 66], p=0 center dot 017). After propensity score weighting, overall clinical response rates remained different between the groups (OR 1 center dot 22 [95% CI 1 center dot 12-1 center dot 33], p<0 center dot 0001). 22 (52%) patients in the ceftriaxone group and 55 (33%) in the benzylpenicillin group had a complete response (crude OR 2 center dot 26 [95% CI 1 center dot 12-4 center dot 41], p=0 center dot 031), with no significant difference after propensity score weighting (OR 1 center dot 08 [95% CI 0 center dot 94-1 center dot 24], p=0 center dot 269). Serological response at 6 months did not differ between the groups (21 [88%] of 24 in the ceftriaxone group vs 76 [82%] of 93 in the benzylpenicillin group; crude OR 1 center dot 56 [95% CI 0 center dot 42-5 center dot 86], p=0 center dot 50), whereas hospital stay was shorter for patients in the ceftriaxone group than for those in the benzylpenicillin group (mean 13 center dot 8 days [95% CI 12 center dot 8-14 center dot 8] vs 8 center dot 9 days [5 center dot 7-12 center dot 0], p<0 center dot 0001). No major adverse effects were reported in either group. Interpretation Our results suggest that ceftriaxone is similarly effective to benzylpenicillin for the treatment of neurosyphilis, potentially decreasing the length of hospital stay. Randomised, controlled trials should be done to confirm these results. Funding None. Copyright (c) 2021 Elsevier Ltd. All rights reserved.