The bacteria that causes gonorrhoea is constantly developing resistance to the drugs used to treat it.
Milos Vujinovic/SOPA Images/LightRocket via Getty Images
Two new antibiotics offer hope for people with gonorrhoea that is resistant to currently available drugs. But it might be years before the people who need these medicines can get them. Spotlight unpacks why these new antibiotics are important and what needs to happen before they can be used in South Africa.Gonorrhoea is a sexually transmitted infection known for its ability to mutate to evade the antibiotics used to treat it quickly. Its symptoms include pain when urinating and genital discharge,but many people don’t notice any symptoms at all.
If gonorrhoea is not treated,it can cause serious problems,including infertility,chronic pain and complications in babies,who risk developing infections that can cause eye damage and blindness.
Gonorrhoea treatment has been a cat-and-mouse game as the bacteria continuously developed resistance against the antibiotics used to treat it. From the 1990s to the early 2000s,the antibiotic ciprofloxacin was used to treat gonorrhoea in South Africa,sometimes combined with another one called doxycycline. However,as high levels of ciprofloxacin resistance emerged,South Africa replaced this course of therapy with a regimen of cefixime and doxycycline. Gonorrhoea treatment was changed again in 2015 due to concerns regarding the emergence of cefixime resistance.
The treatment regimen adopted in 2015 remains the standard of care in South Africa and much of the world today. It involves an intermuscular injection of ceftriaxone combined with oral azithromycin pills. However,some countries now recommend using high-dose injectable ceftriaxone on its own due to high levels of azithromycin resistance.
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While most gonorrhoea cases are still treatable with ceftriaxone,the emergence of ceftriaxone-resistant gonorrhoea has been identified as a significant global health threat.
“The last effective drug we have,ceftriaxone,already indicates increasing gonococcal resistance. Without new antibiotics,we will have no easy treatment options. This is a great concern that will have a major impact in disease control efforts,” warned the World Health Organization (WHO).
READ | There’s a ‘worrying’ resurgence of sexually transmitted infections in Gauteng
That is why two new antibiotics,zoliflodacin and gepotidacin,are considered a big deal. They are the first new medicines developed for gonorrhoea in over 30 years. Both are in new classes of antibiotics,which is to say they attack the bacterium differently than previous medicines. Because of this,they have little cross-resistance with existing treatments and,therefore,offer essential treatment options for people for whom the old medicines no longer work.
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How widespread is ceftriaxone-resistance in South Africa?
How urgently we need access to the new medicines in South Africa will depend largely on the number of people who are resistant to ceftriaxone. Unfortunately,we don’t have a clear picture of drug-resistant gonorrhoea in the country.
South Africa introduced a syndromic management approach for sexually transmitted infections (STIs) in the mid-1990s,as recommended by the WHO. It means that people reporting STI symptoms at health facilities are treated according to their symptoms rather than the results of a lab test.
This approach to STIs helps to reduce the cost burden of laboratory diagnosis. It allows for immediate treatment initiation without waiting for laboratory results since some patients are “lost” over this period as they do not return to health facilities for their test results and treatment.
A challenge with treating STIs according to symptoms rather than laboratory results is that many STIs present with similar symptoms. It can lead to misdiagnosis and incorrect treatment,as well as asymptomatic infections going undiagnosed and untreated.
Thus,without lab testing,combined with routine STI screening to identify asymptomatic cases,it is difficult to understand the actual burden of gonorrhoea in the country or to measure the extent of drug resistance.
A systematic review,however,indicates that while azithromycin resistance is a challenge in South Africa,there was no evidence of ceftriaxone resistance as of 2022.
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The National Institutes of Communicable Diseases (NICD) classified ceftriaxone-resistant gonorrhoea as a notifiable condition in 2017,meaning that any diagnosed cases must be reported to it. The NICD did not respond to a query from Spotlight as to whether there have been any confirmed cases of ceftriaxone-resistant gonorrhoea in South Africa to date.
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While South Africa is not yet facing a ceftriaxone-resistance crisis,experts believe it is only a matter of time before this public health challenge reaches our borders,as global cases are increasing and the drug-resistant strain is transmittable.
Some access to zoliflodacin
Given the risk of a ceftriaxone-resistance crisis,it is essential that the two new antibiotics,become available here as soon as possible. These new antibiotics have quite different histories.
Zoliflodacin was developed by GARDP – a non-profit organisation working to accelerate the development of new antibiotics – in collaboration with the private biopharmaceutical company Innoviva.
In November 2023,GARDP shared the results of its phase 3 trial of zoliflodacin,which took place in South Africa,Thailand,Belgium,the Netherlands and the United States. It tested the effectiveness of a single dose of oral zoliflodacin compared with the current standard of care treatment for gonorrhoea: an injection of ceftriaxone combined with oral azithromycin.
The trial showed that a single dose of zoliflodacin works just as well as the standard of care. The results have not yet been published in a peer-reviewed journal.
Zoliflodacin has also “been shown to be active against all multidrug-resistant strains of Neisseria gonorrhoeae (the gonorrhoea bacteria),including those resistant to ceftriaxone,the last remaining recommended antibiotic treatment”,GARDP’s R&D project leader for STIs,Pierre Daram,told Spotlight.
He added that Innoviva is in the process of applying to get the greenlight to use zoliflodacin in the United States. At the same time,GARDP plans to apply for approval in some of its regions,starting with Thailand and South Africa.
GARDP is also developing a programme to make the unregistered drug available to patients with no other treatment options.
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“The zoliflodacin managed access programme is about to be activated,” Daram said. “The aim is to provide early access to zoliflodacin,prior to regulatory approval in a country,in response to individual patient requests by clinicians and whereby certain regulatory and clinical criteria are met.” South Africa will be one of the countries covered under this programme,said Daram.
He explained that individual patient requests for treatment will be received from treating clinicians through an online platform.
“Based on information provided by the clinician and certain pre-determined regulatory and clinical criteria being met,GARDP will make a case-by-case decision as to whether zoliflodacin will be made available.”
Daram added: “Consideration is given to both clinical and diagnostic criteria for documentation of treatment failure.”
Access to gepotidacin remains uncertain
Shortly after results for zoliflodacin were announced,GlaxoSmithKline (GSK) also shared positive findings for its new antibiotic in treating gonorrhoea. In April 2024,the company reported that a phase 3 trial showed that taking two doses of oral gepotidacin worked as well as the standard treatment.
The results of this trial,which was conducted in Australia,Germany,Mexico,Spain,the United Kingdom,and the United States,were published in the Lancet medical journal in May.
While gepotidacin represents an important new treatment option for gonorrhoea,there is no indication that it will be available in South Africa soon.
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Gepotidacin has not yet been registered for the treatment of gonorrhoea but was approved in March in the United States for treating uncomplicated urinary tract infections (UTIs) in women and girls over 12. Thus,the medicine will have a much larger market in the US than if it was only registered for treating gonorrhoea.
The price that GSK will charge for gepotidacin has not yet been disclosed,but a spokesperson told Spotlight it is set to be launched in the US in the second half of 2025.
“[T]he price in the US will be disclosed when the product will be commercialised,” said the GSK spokesperson.
The company did not respond to Spotlight’s questions about its plans to register and market gepotidacin in South Africa.
What happens next?
With the launch of the zoliflodacin managed access programme,clinicians in South Africa will soon be able to apply for the medicine for patients that are resistant to existing drugs. Given that ceftriaxone-resistance is rare in the country,the number of patients in the country that will be eligible for zoliflodacin is likely to be small.
Securing broader access to zoliflodacin or gepotidacin,potentially for use as a first-line gonorrhoea treatment,appears to be a long way off. While GARDP is planning to file for registration of zoliflodacin in South Africa,GSK has not indicated whether it will follow suit for gepotidacin.
Professor Nigel Garrett,head of HIV pathogenesis and vaccine research at the Centre for the Aids Programme of Research in South Africa,said providing the new antibiotics for first-line gonorrhoea treatment could expand delivery and uptake. The new drugs are both oral tablets and would remove the need for an injection to treat gonorrhoea.
If zoliflodacin and gepotidacin are approved and made affordable in South Africa,they could also play a vital role in strengthening the country’s efforts to preserve the long-term effectiveness of other antibiotics.
Ceftriaxone “is a really important drug to keep,[to] make sure that there isn’t too much resistance against it”,Garrett told Spotlight. He explained that the medicine is needed to treat sepsis occurring in hospitals,as well as meningitis.
This article was first published by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.
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