O20.2 Ertapenem is non-inferior to ceftriaxone for the treatment of anogenital gonorrhea: the NABOGO randomized double blind non-inferiority trial

Abstract

<h3>Background</h3> Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging strains resistant to first-line ceftriaxone threaten Ng management. Hence, alternative treatments are needed. We evaluated the efficacy of ertapenem, gentamicin and fosfomycin as alternatives for Ng. <h3>Approach</h3> We included adults 18 years or older, with anorectal or urogenital gonorrhea in a randomized controlled, double-blind, non-inferiority trial (three experimental- and one control-arm). Participants were randomized (1:1:1:1) to receive: intramuscular (IM) 500mg ceftriaxone, IM 1000mg ertapenem, IM 5mg/kg gentamicin (maximum 400mg), or 6g fosfomycin orally. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the primary infected site, 7–14 days after treatment. Non-inferiority was established if the lower Hochberg-corrected 95% confidence interval for difference between experimental and control arms was greater than -10%. <h3>Outcomes</h3> Between 18 September 2017 and 5 June 2020, we assigned 346 participants to ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), and fosfomycin (n=38). The fosfomycin arm was terminated early after interim analysis revealed &lt;60% efficacy. In the primary modified intent-to-treat (mITT) analysis, all patients (93/93) in the ceftriaxone, 99% (86/87) in the ertapenem, 93% (79/85) in the gentamicin, and 12% (4/33) in the fosfomycin arm cleared Ng [risk difference, ertapenem versus ceftriaxone, -0.01(95 CI: -0.06,0.03); gentamicin versus ceftriaxone -0.07(95%CI: -0.16,-0.005)]. Both the secondary mITT analysis (clearance within 7–28 days), and the per-protocol analyses were consistent with the primary mITT analysis. <h3>Significance</h3> Single-dose 1000mg ertapenem is non-inferior to single-dose 500mg ceftriaxone in gonorrhea treatment. Given that ertapenem, an already registered antibiotic, is non-inferior to the standard of care, it may currently provide an alternative treatment option for gonorrhea if resistance against ceftriaxone becomes more widespread.