Gentamicin–azithromycin combination could be effective for drug-resistant gonorrhea

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New research has suggested that a treatment of gentamicin with azithromycin was almost as effective as the currently used ceftriaxone for treating genital gonorrhea.

Among growing concerns of ceftriaxone resistance, the study, which was funded by the National Institute for Health Research (NIHR) and published in The Lancet, is the first randomized controlled trial to compare these two treatments for gonorrhea.

Chief investigator, Jonathan Ross (University Hospitals Birmingham, UK) commented: “”Our current antibiotic treatment for gonorrhea is beginning to fail and experience with previous drugs strongly suggests that this could become a widespread problem.”

The trial was performed in 14 sexual health clinics across England, with 720 participants randomized to either receive gentamycin injections or intravenous ceftriaxone, alongside oral azithromycin in both groups.

The researchers discovered that 98% of patients given ceftriaxone were cured of their gonorrhea, compared with 91% in the gentamycin group. The findings make it likely that ceftriaxone will continue as the preferred treatment, however, gentamycin had a cure rate of 94% in genital gonorrhea, suggesting it could be an alternative. Ross explained: “Our trial has found that gentamicin combined with azithromycin works almost as well as ceftriaxone with azithromycin for genital gonorrhea but did not clear throat or rectal gonorrhea as effectively.”

“We believe ceftriaxone should remain the first-line treatment for gonorrhea, with gentamicin as an alternative particularly for patients with genital infection, and those who are allergic or intolerant to ceftriaxone. But further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhea.”

The study also indicated that the current 1g dose of azithromycin is probably not enough to prevent resistance developing, and it’s use globally as part of combination therapy should be reviewed. In January this year the British Association for Sexual Health and HIV changed the national gonorrhea treatment guideline to omit the azithromycin (and use a larger dose of ceftriaxone instead) to reflect the trial results.

The team state that further research into developing a preventative or therapeutic vaccine is crucial due to combat increasing resistance and limited treatment options.

Hywel Williams, Director of the NIHR’s Health Technology Assessment Program, concluded: “It’s very worrying that cases of treatment resistant gonorrhea are now appearing across the globe. This research provides important new evidence that suggests that gentamicin with azithromycin could become a second-line treatment for patients who are resistant to ceftriaxone with this infectious disease.”

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Source: Ross JDC, Brittain C, Cole M et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial. Lancet 393(10190, 2511–2520 (2019); www.nihr.ac.uk/news/drug-combination-could-be-effective-for-treatment-resistant-gonorrhoea/20343

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