Antibiotic-resistant gonorrhea is a growing problem worldwide. The first signs of resistance to the current standard drug ceftriaxone have now been demonstrated. Is there an alternative that can be found if resistance really does take hold and gonorrhea becomes untreatable as a result? Maarten Schim van der Loeff and his team found a solution - just in case.

'STI clinics recorded about 6,700 cases of gonorrhea in 2020. The treatment of this disease has always been a story of resistance. A long time ago, penicillin was used, until it stopped working. Now we are a few antibiotics further along and there are signs that the rapidly mutating gonorrhea bacteria are threatening to become resistant to ceftriaxone, the current drug. According to the WHO, if more than 5% of the circulating strains of bacteria become resistant, you can no longer use an antibiotic as a first-line drug in the STI clinic. We haven't reached that point yet, but we wanted to look for an alternative now.'

How did you approach the study?

'We compared the standard drug - which has a perfect track record - with three other antibiotics. We did this double-blind among 310 gonorrhoea patients from the STI outpatient clinic of the GGD Amsterdam. Gentamicin is an old drug that has shown good results in Africa. But it lacked trial data to substantiate its effectiveness. Ertapenem emerged as promising in lab research. And phosphomycin, which is used for urinary tract infections, also looked good in small studies. Our trial had to show whether the expectations could be substantiated in clinical practice.'

What were the results?

'Phosphomycin quickly proved ineffective. Gentamicin cured the majority of patients of their gonorrhea, but not as well as ceftriaxone. Ertapenem did turn out to be a full-fledged alternative, in case resistance to ceftriaxone did indeed continue. History shows that this is a matter of time. And that also implies that the problem has not been definitively solved. We will probably have to keep looking for alternatives, because the bacteria - while mutating - keep escaping from drugs. Ertapenem will remain on the shelf for the time being. But in the meantime we have to arrange admission and reimbursement because the drug is not yet registered for the European market for intramuscular administration. We have had an initial discussion with the manufacturer, who should initiate the authorisation procedure.'

How do the results affect the guideline?

The existing multidisciplinary STI guideline is due for revision. Our results will certainly be on the agenda for that. So the motto should probably be not to change anything now and not to implement the other tool yet. I've noticed that it's very difficult to explain this to people. Research funders - including ZonMw - want studies to improve care. And in this case, 'better' means doing nothing new for a while.

What can you say about collaboration?

'This trial is an initiative of the Amsterdam Municipal Health Service, but the three principal investigators also work for Amsterdam UMC. My suggestion: this kind of research only succeeds if clinicians, microbiologists and epidemiologists do it together.'

The NABOGO-trial was conducted by a research team led by Prof. Dr. Maarten Schim van der Loeff, physician and epidemiologist at GGD Amsterdam and special professor of Epidemiology of sexually transmitted infections at the University of Amsterdam (UvA), and dermatologist-venerologist Henry de Vries (professor at Amsterdam UMC). They did the study together with medical microbiologist Alje van Dam (also Amsterdam UMC). They were statistically supported by epidemiologist Mirjam Knol of RIVM and Anders Boyd and Vita Jongen of GGD Amsterdam.

Text: Marc van Bijsterveldt (November 2021), you can find the original (Dutch) text here.