Lancet Infect Dis

Oral linezolid vs. benzathine penicillin G for early syphilis

January 17, 2024

Linezolid (600 mg PO daily for 5 days) didn’t meet non-inferiority criteria compared with benzathine penicillin G (BPG).

• Trep-AB was a multicenter, open-label, non-inferiority RCT in which researchers recruited participants with serological or molecular confirmation of syphilis (primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia, Spain. Participants were randomly allocated in a 1:1 ratio to receive either oral linezolid (600 mg once daily for 5 days) or IM BPG (single dose of 2.4 million IU) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). Primary endpoint was treatment response, assessed using a composite endpoint including clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a 4-fold decline in RPR titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. Absence of relapse was defined as the presence of different molecular sequence types of T. pallidum in recurrent syphilis.
• Between Oct 2021 and Sept 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' of follow-up, the rate of treatment response was 70% in the linezolid group vs. 100% in the BPG group, which did not meet the non-inferiority criterion. The rate of drug-related adverse events (all mild or moderate) was similar (17%) in both treatment groups. No serious adverse events were reported during follow-up.
• Given the findings, authors conclude that the use of linezolid 600 mg per day for 5 days is not recommended to treat patients with early syphilis. They do concede, however, that linezolid has intrinsic advantages relative to penicillin and believe that investigating the efficacy of a higher-dose and longer-duration regimens is worthwhile.

Source:

Ubals M, et al. (2024, January 8). Lancet Infect Dis. Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial. https://pubmed.ncbi.nlm.nih.gov/38211601/