Background Cephalosporins are the mainstay of recommended gonorrhoea treatment, and there is an urgent need for treatment options for cephalosporin-allergic patients or infections with suspected cephalosporin resistance. We evaluated the efficacy and tolerability of two novel combinations of existing antimicrobials for treatment of uncomplicated urogenital gonorrhoea.

Methods We conducted a non-comparative trial, randomising patients with urogenital gonorrhoea to one of two regimens: gentamicin 240 mg intramuscularly plus azithromycin 2 g orally (GENT/AZI), or gemifloxacin 320 mg orally plus azithromycin 2 g orally (GEMI/AZI). The primary outcome was microbiologic cure of urogenital infections (negative follow-up culture) at 10–17 days post-treatment. All participants who returned for follow-up and had evaluable follow-up cultures were included in this per protocol analysis.

Results For 401 evaluable participants (GENT/AZI-202; GEMI/AZI-199), the mean age of both groups was 30 years. Most participants were heterosexual men (GENT/AZI, 57%; GEMI/AZI, 51%), followed by men who have sex with men (GENT/AZI, 33%; GEMI/AZI, 39%), and women (GENT/AZI, 9%; GEMI/AZI, 11%). Microbiological cure was achieved by 100% (lower one-sided 95% confidence interval, 98.5%) of GENT/AZI participants, and 99.5% (lower one-sided 95% confidence interval, 97.6%) of GEMI/AZI participants. GENT/AZI cured 10/10 pharyngeal and 1/1 rectal infections; GEMI/AZI cured 15/15 pharyngeal and 5/5 rectal infections. In the GENT/AZI arm, the most common adverse events (AEs) were mild-moderate nausea (27% of participants), diarrhoea (19%), abdominal discomfort/pain and vomiting (both 7%). In the GEMI/AZI arm, the most common AEs were nausea (37% [8% moderate-severe]), diarrhoea (23%), and abdominal discomfort/pain (11%).

Conclusions Both study regimens were highly effective. Gastrointestinal AEs, especially nausea and diarrhoea, were common. These results provide alternative gonorrhoea treatment options for patients who cannot be treated with cephalosporins.