Diarrhoea as a frequent adverse event after intramuscular ertapenem treatment for uncomplicated Neisseria gonorrhoeae : a secondary analysis from the NABOGO trial

Objectives The New AntiBiotic treatment Options for uncomplicated GOnorrhoea trial compared the efficacy of gentamicin, ertapenem and fosfomycin with ceftriaxone. Ertapenem was non-inferior to ceftriaxone for treating Neisseria gonorrhoeae , but participants receiving ertapenem commonly reported having diarrhoea. We assessed diarrhoea trajectories, estimated the probability of remaining with diarrhoea over time and identified determinants of diarrhoea. Methods Participants were randomly assigned (1:1:1:1) to receive intramuscular 5 mg/kg gentamicin (maximum 400 mg), intramuscular 1000 mg ertapenem, oral 6 g fosfomycin or intramuscular 500 mg ceftriaxone (control group). Following antibiotic treatment, participants self-reported adverse events, including diarrhoea, in a paper diary until 30 days after treatment. In this secondary analysis, we assessed the frequency of diarrhoea in each study arm. Kaplan-Meier methods were used to estimate the probability of remaining with diarrhoea over time in each study arm. Determinants of diarrhoea in the ertapenem arm were assessed using relative risk regression. Results Among 343 participants randomised, 2/102 (2.0%) in the gentamicin arm, 49/97 (50.5%) in the ertapenem arm, 32/37 (86.5%) in the fosfomycin arm and 11/103 (10.7%) in the ceftriaxone arm reported diarrhoea. Median duration of diarrhoea varied between 1 and 2 days across arms. In the ertapenem arm, only having an anal N. gonorrhoeae and/or anal Chlamydia trachomatis infection (prevalence ratio=2.29, 95% CI 1.04 to 5.02) was associated with increased diarrhoea risk. Conclusions Ertapenem was associated with high frequency of diarrhoea, which was mostly short-lived. Continued evaluation of the tolerability of ertapenem could help increase acceptability of this potential second-line treatment against N. gonorrhoeae . Trial registration number NCT03294395 .