A new drug combination - gentamicin with azithromycin - could be an effective back-up for patients not responding to current therapy for gonorrhoea, shows a paper* published in The Lancet.
The study, funded by the National Institute for Health Research (NIHR), involved 720 patients at 14 sexual health clinics in England who were randomised to receive either injections of gentamicin, or the current treatment of ceftriaxone intravenously, with both groups also given a single dose of azithromycin by mouth.
Overall 98% of participants given ceftriaxone had their gonorrhoea cured, compared to 91% given gentamicin, a difference of 7%. Therefore, it is likely that doctors will continue to use ceftriaxone (plus azithromycin) as their preferred treatment. Gentamicin did have a cure rate of 94% for genital gonorrhoea and so it might be useful when ceftriaxone is not available, or inappropriate to use.
The study also indicates that current widely used treatment of 1 gram azithromycin, used in combination with both drugs, is probably not enough to prevent resistance developing, and its use globally as part of dual combination therapy for gonorrhoea should be reviewed. In January this year the British Association for Sexual Health and HIV changed the national gonorrhoea treatment guideline to omit the azithromycin (and use a larger dose of ceftriaxone instead) to reflect the trial results.
Chief investigator Professor Jonathan Ross from University Hospitals Birmingham said: "Our current antibiotic treatment for gonorrhoea is beginning to fail and experience with previous drugs strongly suggests that this could become a widespread problem. Our trial has found that gentamicin combined with azithromycin works almost as well as ceftriaxone with azithromycin for genital gonorrhoea, but did not clear throat or rectal gonorrhoea as effectively.
"We believe ceftriaxone should remain the first-line treatment for gonorrhoea, 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 gonorrhoea."
Public Health England recently reported that it was investigating two cases of gonorrhoea in two women with similar resistance patterns to the antibiotics ceftriaxone and azithromycin. One of these cases appears to have been contracted in Europe and the other has links to Europe but was acquired in the UK. A case of resistant gonorrhoea was contracted in South East Asia by a UK national in 2018. This was a different type of resistance and unrelated.
Professor Hywel Williams, director of the NIHR's Health Technology Assessment Programme, said: "It's very worrying that cases of treatment-resistant gonorrhoea 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.”
*Ross JDC, Brittain C, Cole M, et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial. The Lancet, 2 May 2019, DOI:10.1016/S0140-6736(18)32817-4