Gentamicin Found Inferior to Ceftriaxone for Gonorrhea Treatment

Ceftriaxone remains the superior first-line treatment for gonorrhea compared with gentamicin, according to a study published in The Lancet.

Gonorrhea accounts for approximately 78 million infections globally with a disproportionate number of these infections affecting young adults, men who have sex with men, and specific ethnic groups. Infection with gonorrhea can lead to inflammation causing genital pain, localized immune activation that facilitates that transmission and acquisition of HIV, and pelvic inflammatory disease that can result in infertility and increased risk for ectopic pregnancy. Neisseria gonorrhoeae is the causative organism for this infection and has been shown to readily develop antibiotic resistance.

Currently, ceftriaxone is the first-line treatment for gonorrhea infection, but if resistance causes ceftriaxone to be ineffective, there are limited treatment options. Previous in vitro studies shown that resistant N gonorrhoeae may be susceptible to gentamicin, however, in vivo response data are lacking. Therefore, this multicenter, parallel-group, randomized, noninferiority trial assessed the effectiveness of azithromycin combined with gentamicin as an alternative to azithromycin combined with ceftriaxone for treatment of gonorrhea (ISRCTN identifier: ISRCTN51783227).

In total, 720 patients diagnosed with uncomplicated genital, pharyngeal, or rectal gonorrhea aged 16 to 70 years were included from 14 sexual health clinics in England. Patients were randomly assigned (1:1) to receive a single 1-g dose of azithromycin with a single intramuscular dose of either ceftriaxone 500 mg (n=362) or gentamicin 240 mg (n=358). The primary outcome was clearance of N gonorrhoeae at all initially infected sites, which was defined as a negative nucleic acid amplification test 2 weeks post-treatment. Primary outcome analyses included only patients who had follow-up data, regardless of the baseline visit N gonorrhoeae test result, and was available for 85% of the ceftriaxone group and 82% of the gentamicin group.

Of patients who had genital, pharyngeal, and rectal infection, gentamicin was shown to be inferior in clearing gonorrhea: 2 weeks post-treatment results showed that infection had cleared in 98% of the ceftriaxone group and 91% of the gentamicin group. A total of 328 patients had a genital infection. Of these, 98% in the ceftriaxone group had clearance at follow-up, while 74% in the gentamicin group demonstrated clearance at follow-up. Further, of participants with pharyngeal infection, 96% of those in the ceftriaxone group and 80% of the gentamicin group had clearance of infection at the time of follow-up. Among patients with rectal infection, 98% of those in the ceftriaxone group demonstrated clearance of infection at follow-up, and 90% in the gentamicin group achieved the same. However, the side effect profiles were similar between both treatment arms, but severity of injection site pain was higher for the gentamicin group.

Overall, the study authors concluded that, “Gentamicin is not appropriate as first-line treatment for [gonorrhea] but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbor a ceftriaxone-resistant isolate.”

Reference

Ross JD, Brittain C, Cole M, et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial [published online May 2, 2019]. Lancet. doi:10.1016/S0140-6736(18)32817-4