NIH-funded clinical trial shows potential to simplify treatment for early syphilis.
Photo by Raghavendra V Konkathi on Unsplash
Researchers funded by the National Institutes of Health (NIH) have found that a single injection of the antibiotic benzathine penicillin G (BPG) successfully treated early syphilis just as well as the three-injection regimen used by many clinicians in the United States and elsewhere. These findings from a late-stage clinical trial suggest the second and third doses of conventional BPG therapy do not provide a health benefit. The results were published in The New England Journal of Medicine.
“Benzathine penicillin G is highly effective against syphilis, but the three-dose regimen can be burdensome and deter people from attending follow-up visits with their healthcare providers,” said Carolyn Deal, PhD, chief of the enteric and sexually transmitted infections branch of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “The new findings offer welcome evidence for potentially simplifying treatment with an equally effective one-dose regimen, particularly while syphilis rates remain alarmingly high.”
Syphilis is a common sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. The United States reported 209 253 total syphilis cases and 3882 congenital syphilis cases in 2023, representing 61% and 108% increases over 2019 numbers, respectively. Without treatment, syphilis can result in neurological and organ damage as well as severe pregnancy complications and congenital abnormalities. Syphilis can also increase a person’s likelihood of acquiring or transmitting HIV.
BPG is one of the few antibiotics known to effectively treat syphilis, and stockouts are common worldwide. The antibiotic is currently being imported to the United States to resolve a nationwide shortage.
The study was conducted at ten U.S. sites and enrolled 249 participants with early syphilis, which encompasses the primary, secondary, and early latent stages of disease. Sixty-four percent of participants were living with HIV and 97% were men. The participants were randomly assigned to receive either a single intramuscular (IM) injection of BPG 2.4 million units (MU) or a series of three IM injections of BPG 2.4 MU at weekly intervals. All participants were monitored for safety. Biological markers of successful treatment in the blood – known as the serologic response to therapy – were examined at six months following treatment.
Seventy-six percent of participants in the single-dose group had a serologic response to treatment compared to 70% of participants in the three-dose group. The difference between groups was not statistically significant, even when participants were stratified by HIV status. One participant developed signs of neurosyphilis three days after starting BPG therapy and was excluded from the analysis. Three serious adverse events were reported but were not related to BPG.
“Syphilis has been studied and treated for more than a century, and BPG has been in use for more than 50 years, yet we are still acquiring knowledge to help us optimise treatment,” said Principal Investigator Edward W. Hook III, MD, emeritus professor of medicine and epidemiology at the University of Alabama at Birmingham. “We hope these promising results will be complemented by scientific advances in syphilis prevention and diagnosis.”
According to the study authors, the results from this trial provide substantial evidence that single-dose BPG 2.4 MU is as effective as three doses in treating early syphilis. More research is needed to understand the full potential of this abbreviated treatment strategy and to evaluate therapeutic approaches for all stages of syphilis, including late syphilis, latent syphilis of unknown duration, and clinical neurosyphilis.
The study was conducted through the NIAID-funded Sexually Transmitted Infections Clinical Trials Group.
For more information about this trial, please visit ClinicalTrials.gov using the study identifier NCT03637660.
New research from the University of South Australia shows that the trusted staples of paracetamol and ibuprofen are quietly fuelling one of the world’s biggest health threats: antibiotic resistance.
In the first study of its kind, researchers found that ibuprofen and paracetamol are not only driving antibiotic resistance when used individually but amplifying it when used together.
Assessing the interaction of non-antibiotic medications, the broad-spectrum antibiotic ciprofloxacin, and Escherichia coli, researchers found that ibuprofen and paracetamol significantly increased bacterial mutations, making E. coli highly resistant to the antibiotic.
It’s an important finding that has serious health implications, particularly for people in aged care homes, where multiple medications are regularly administered.
Lead researcher UniSA’s Associate Professor Rietie Venter says the findings raise important questions about the risks of polypharmacy in aged care.
“Antibiotics have long been vital in treating infectious diseases, but their widespread overuse and misuse have driven a global rise in antibiotic-resistant bacteria,” Assoc Prof Venter says.
“This is especially prevalent in residential aged care facilities, where older people are more likely to be prescribed multiple medications – not just antibiotics, but also drugs for pain, sleep, or blood pressure – making it an ideal breeding ground for gut bacteria to become resistant to antibiotics.
“In this study we looked at the effect of non-antibiotic medicines and ciprofloxacin, an antibiotic which is used to treat common skin, gut or urinary tract infections.
“When bacteria were exposed to ciprofloxacin alongside ibuprofen and paracetamol, they developed more genetic mutations than with the antibiotic alone, helping them grow faster and become highly resistant. Worryingly, the bacteria were not only resistant to the antibiotic ciprofloxacin, but increased resistance was also observed to multiple other antibiotics from different classes.
“We also uncovered the genetic mechanisms behind this resistance, with ibuprofen and paracetamol both activating the bacteria’s defences to expel antibiotics and render them less effective.”
Assoc Prof Venter says the study shows how antibiotic resistance is a more complex challenge than previously understood, with common non-antibiotic medications also playing a role.
“Antibiotic resistance isn’t just about antibiotics anymore,” Assoc Prof Venter says.
“This study is a clear reminder that we need to carefully consider the risks of using multiple medications – particularly in aged care where residents are often prescribed a mix of long-term treatments.
“This doesn’t mean we should stop using these medications, but we do need to be more mindful about how they interact with antibiotics – and that includes looking beyond just two-drug combinations.”
The researchers are calling for further studies into drug interactions among anyone on long-term medication treatment regimes so we can gain a greater awareness of how common medications may impact antibiotic effectiveness.
Korean children with early life exposure to antibiotics were not diagnosed with autoimmune diseases at higher rates
Photo by Chayene Rafaela on Unsplash
The global incidence of autoimmune diseases among children has increased over the past few decades. A study published August 21st in the open-access journal PLOS Medicine by Ju-Young Shin at Sungkyunkwan University, Republic of Korea, and colleagues suggests that early life antibiotic exposure is not associated with an increased risk of autoimmune diseases in children.
Previous research has suggested that exposure to antibiotics as a foetus or infant may contribute to the development of autoimmune diseases among children. However, confounding variables limit the validity of prior studies and the association of antibiotics to autoimmune disease remains poorly understood.
In order to investigate whether antibiotics may increase risk of autoimmune diseases, researchers conducted a retrospective cohort study comprised of over 4 million children born in the Republic of Korea between April 1, 2009, and December 31, 2020. They accessed a mother-child linked insurance claims database from the South Korea National Health Insurance Service-National Health Insurance Database (NHIS-NHID) to identify children whose mothers had received antibiotic prescriptions during pregnancy or while breastfeeding their infant. The researchers then retrospectively analysed the health outcomes of each cohort for a period of over 7 years, tracking all diagnoses of Type 1 diabetes, Juvenile idiopathic arthritis, Inflammatory bowel disease (ulcerative colitis, Crohn’s disease), Systemic lupus erythematosus, and Hashimoto’s thyroiditis.
The researchers found no relationship between antibiotic exposure during pregnancy or early infancy and the overall incidence of autoimmune diseases in children. Future research is needed, however, to replicate the outcomes in other populations and to further investigate potential effects on subgroups.
According to the authors, “Our findings suggest no association between antibiotic exposure during the prenatal period or early infancy and the development of autoimmune diseases in children. This observation contrasts with several previous studies reporting increased risks and underscores the importance of carefully considering the underlying indications for antibiotic use and genetic susceptibility when interpreting such associations. While the potential benefits of antibiotic treatment in managing infections during pregnancy or early infancy likely outweigh the minimal risk of autoimmune outcomes, our findings also highlight the need for cautious and clinically appropriate use of antibiotics during these critical developmental periods in specific subgroups.”
The authors note, “Exposure to antibiotics during pregnancy or early infancy was not associated with an increased risk of autoimmune diseases in children. Nevertheless, the importance of follow-up studies to confirm and extend these findings cannot be overstated.”
Preterm babies with very low birth weight who received a probiotic alongside antibiotics had fewer multidrug resistant bacteria and a more typical gut microbiome, a new study shows.
The paper published in Nature Communications is the result of a trial testing probiotics among a group of 34 pre-term babies born with a very low birth weight, under 1500g representing around 1-1.5% of babies born around the world. The study sequenced gut bacteria from the babies during the first three weeks after birth.
The collaborative study led by Professor Lindsay Hall and Dr Raymond Kiu from the University of Birmingham found that among babies who received a probiotic treatment of a certain strain including Bifidobacterium alongside antibiotics, levels of typical bacterial strains associated with early-life gut microbiota were at levels typical among full-term babies, reducing both the abundance of antibiotic resistance genes and the number of multi-drug resistant bacteria in the gut.
In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies. Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.Professor Lindsay Hall – University of Birmingham
There were lower levels of drug-resistant pathogens including Enterococcus associated with risks of infections and longer hospital stays. Babies who received probiotics also saw higher levels of certain positive bacteria found naturally in the gut.
Among babies who didn’t receive probiotics, analysis of the gut bacteria found that while some differences occurred between those receiving antibiotics or not, both groups saw a dominant microbiome develop that included key bacteria (pathobionts) that can cause health problems including life-threatening infections during the crucial period after birth, as well as in later life.
Professor Lindsay Hall from the University of Birmingham and a group leader at Quadram Institute Bioscience, and senior corresponding author of the study said: “We have already shown that probiotics are highly effective in protecting vulnerable preterm babies from serious infections, and this study now reveals that these probiotics also significantly reduce the presence of antibiotic resistance genes and multidrug-resistant bacteria in the infant gut. Crucially, they seem to do so selectively – targeting resistant strains without disrupting non-resistant strains that might be beneficial.
“In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies.
“Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.”
Dr Raymond Kiu from the University of Birmingham, first and co-corresponding author of the paper said: “Sequencing technology has now confirmed that probiotic Bifidobacterium rapidly replicates in the preterm gut during the first three weeks of life. Importantly, this successful colonisation drives the maturation of the gut microbiota and is linked to a noticeable reduction in multi-drug-resistant pathogens – pointing to its pivotal role in improving neonatal health. Our findings also shed light on the complex interactions between antibiotics, probiotics, and horizontal gene transfer (HGT) in shaping the early-life microbiome.
“We believe this research lays the groundwork for future studies exploring the role of probiotics in antimicrobial stewardship and infection control among preterm populations.”
Antibiotics are supposed to wipe out bacteria, yet the drugs can sometimes hand microbes an unexpected advantage.
A new Nature Communications study from Rutgers Health shows that ciprofloxacin, a staple treatment for urinary tract infections, throws Escherichiacoli into an energy crisis that saves many cells from death and speeds the evolution of full‑blown resistance.
“Antibiotics can actually change bacterial metabolism,” said first author Barry Li, a student at Rutgers pursuing a dual doctoral degree for physician–scientists. “We wanted to see what those changes do to the bugs’ chances of survival.”
Li and senior author Jason Yang focused on adenosine triphosphate (ATP), the molecular fuel of cells. When ATP levels crash, cells experience “bioenergetic stress.” To mimic that stress, the team engineered E. coli with genetic drains that constantly burned ATP or its cousin nicotinamide adenine dinucleotide (NADH). Then, they pitted both the engineered strains and normal bacteria against ciprofloxacin.
The results surprised the researchers. The drug and the genetic drains each slashed ATP, but rather than slowing down, the bacteria revved up. Respiration soared, and the cells spewed extra reactive‑oxygen molecules that can damage DNA. That frenzy produced two troubling outcomes.
First, more of the bacteria cells survived.
In time‑kill tests, ten times as many stressed cells survived a lethal ciprofloxacin dose compared with unstressed controls. These hardy stragglers, called persister cells, lie low until the drug is gone and then rebound to launch a new infection.
People have long blamed sluggish metabolism for persister cell formation.
“People expected a slower metabolism to cause less killing,” Li said. “We saw the opposite. The cells ramp up metabolism to refill their energy tanks, and that turns on stress responses that slow the killing.”
Follow‑up experiments traced the protection to the stringent response, a bacterial alarm system that reprograms the cell under stress.
Second, stressed cells mutated faster to evolve antibiotic resistance.
While persisters keep infections smoldering, genetic resistance can render a drug useless outright. The Rutgers group cycled E. coli through escalating ciprofloxacin doses and found that stressed cells reached the resistance threshold four rounds sooner than normal cells. DNA sequencing and classic mutation tests pointed to oxidative damage and error‑prone repair as the culprits.
“The changes in metabolism are making antibiotics work less well and helping bacteria evolve resistance,” said Yang, an assistant professor at the medical school and Chancellor Scholar of microbiology, biochemistry & molecular genetics.
Preliminary measurements show that gentamicin and ampicillin also drain ATP in addition to ciprofloxacin. The stress effect may span very different pathogens, including the pathogen Mycobacterium tuberculosis, which is highly sensitive to ATP shocks.
If so, the discovery casts new light on a global threat. Antibiotic resistance already contributes to 1.27 million deaths a year. Strategies that ignore the metabolic fallout of treatment may be missing a key lever.
The findings suggest several changes for antibiotic development and use.
First, screen candidate antibiotics for unintended energy‑drain side effects. Second, pair existing drugs with anti‑evolution boosters that block the stress pathways or mop up the extra oxygen radicals. Third, reconsider the instinct to blast infections with the highest possible dose. Earlier studies and the new data both hint that extreme concentrations can trigger the very stress that protects bacteria.
“Bacteria turn our attack into a training camp,” Yang said. “If we can cut the power to that camp, we can keep our antibiotics working longer.”
Li and Yang are planning on testing compounds that soothe bioenergetic stress in the hope of turning the microbial energy crisis back into an Achilles’ heel rather than a shield.
A group of infectious disease and public health experts are calling on the Department of Health and Minister Aaron Motsoaledi to reintroduce a national action plan addressing antimicrobial resistance (AMR).
An open letter from over 70 doctors, scientists and public health advisors states that antibiotic resistance is becoming a “growing threat” in the country and poses a threat to universal health coverage through the National Health Insurance.
Latest figures show that over one-million deaths a year worldwide are directly caused by AMR. This number is projected to increase. Nearly five-million people die with an antibiotic-resistant infection. Over the next 25 years, nearly 40-million people are projected to die from AMR.
The open letter also called on the department to reinstate a ministerial advisory committee on AMR or to establish a similar scientific body.
“The lack of a robust scientific advisory body limits the government’s capacity to develop evidence-based policies,” the letter reads. The establishment of a scientific body would “empower the government to make strategic, data-driven decisions to combat this pressing health threat effectively”.
The former Ministerial Advisory Committee was disbanded in November 2023.
Marc Mendelson, an infectious disease specialist at Groote Schuur Hospital who has been outspoken about the threat of AMR for many years, said: “AMR is a current pandemic which is wreaking havoc, is not being attended to properly and not being taken seriously enough in South Africa.”
Mendelson said that there are “more and more people having to be treated for highly resistant bacterial infections in our healthcare system”. AMR leads to an increase in morbidity, mortality, hospital costs, and also has socio-economic consequences, he said. Common medical interventions such as surgery “becomes much riskier” with AMR.
Department of Health spokesperson Foster Mohale said that the department would only comment once the letter was formally presented, which is expected to happen at 5pm on Thursday.
A study of almost 1000 pregnant women in Zimbabwe found that a daily dose of a commonly used, safe and inexpensive antibiotic may have led to fewer babies being born early. Among women living with HIV, those who received the antibiotic had larger babies who were less likely to be preterm.
One in four live-born infants worldwide is preterm (born at 37 weeks’ gestation or before), is small for gestational age, or has a low birth weight. The mortality rate for these small and vulnerable newborns is high, with prematurity now the leading cause of death among children younger than 5 years of age. Maternal infections and inflammation during pregnancy are linked to adverse birth outcomes, particularly for babies born to mothers living with HIV, who have a greater risk of being born too small or too soon.
An international group of researchers, led by Professor Andrew Prendergast from Queen Mary University of London, and Bernard Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, conducted the Cotrimoxazole for Mothers to Improve Birthweight in Infants (COMBI) randomised controlled trial, to examine whether prescribing pregnant women a daily dose of trimethoprim–sulfamethoxazole (a broad-spectrum antimicrobial agent with anti-inflammatory properties, widely used in sub-Saharan Africa) would result in heavier birth weights, decreased premature births, and better health outcomes for their babies.
993 pregnant women were recruited from three antenatal clinics in Shurugwi, a district in central Zimbabwe, and received either 960 mg of the drug or a placebo daily. The participants received regular antenatal care during their pregnancies and data regarding their birth outcomes were recorded.
The study, published in the New England Journal of Medicine, found that although birthweight did not differ significantly between the two groups, the trimethoprim–sulfamethoxazole group showed a 40% reduction in the proportion of preterm births, compared to the placebo group. Overall, 6.9% of mothers receiving the drug had babies born preterm, compared to 11.5% of mothers receiving the placebo, and no women receiving antibiotics had babies born prior to 28 weeks. For babies born to a small group of 131 women with HIV, the reduction in premature births was especially marked, with only 2% of births in the trimethoprim–sulfamethoxazole group preterm, as compared with 14% in the placebo group. Babies exposed to antibiotics during pregnancy also showed a 177 gram increase in their birth weight.
Bernard Chasekwa, first author, said: “Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome. However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”
Neisseria gonorrhoeae Bacteria Scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea. Captured by the Research Technologies Branch (RTB) at the NIAID Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID. Photo by National Institute of Allergy and Infectious Diseases on Unsplash
By Catherine Tomlinson
Two new antibiotics offer hope for people with gonorrhoea that is resistant to currently available drugs. Yet, 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 quickly mutate to evade the antibiotics used to treat it. 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 something of 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. But 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. Although, some countries now recommend using high dose injectable ceftriaxone on its own, due to high levels of azithromycin resistance.
While most gonorrhoea cases are still treatable with ceftriaxone, the emergence of ceftriaxone-resistant gonorrhoea has been identified as a major 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).
This is why two new antibiotics, zoliflodacin and gepotidacin, are considered such 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 in a different way than previous medicines. Because of this, they have little cross resistance with existing treatments and therefore offer important treatment options for people for whom the old medicines no longer work.
How widespread is ceftriaxone-resistance in South Africa?
How urgently we need access to the new medicines in South Africa will depend largely on how many people here 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. This means that people reporting STI symptoms at health facilities are treated according to their symptoms, rather than results of a lab test.
This approach to STIs helps to reduce the cost burden of laboratory diagnosis and 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. This 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 true 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 not yet evidence of ceftriaxone resistance as of 2022.
The National Institutes of Communicable Diseases (NICD) classified ceftriaxone-resistant gonorrhoea 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.
While South Africa is not yet facing a ceftriaxone-resistance crisis, experts are of the view that 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 important that the two new antibiotics, zoliflodacin and gepotidacin, 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 – together 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, which is 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 is planning to apply for approval in some of its own regions, starting with Thailand and South Africa.
GARDP is also working on a programme to make the unregistered drug available for patients who have no other treatment options.
“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 as well as 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 their 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 just 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 any time soon.
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. The medicine will thus 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 commercialized,” said the GSK spokesperson.
The company did not respond to Spotlight’s questions regarding the company’s 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 they will follow suit for gepotidacin.
Providing the new antibiotics for first line gonorrhoea treatment could expand delivery and uptake, as the new drugs are both oral tablets and would remove the need for an injection to treat gonorrhoea, said Professor Nigel Garrett, who is the Chief Scientific Officer at the Desmond Tutu Health Foundation.
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,” Garret told Spotlight. He explained that the medicine is needed to treat sepsis occurring in hospitals, as well as meningitis.
Jorunn Pauline Cavanagh holds up a petri dish with the newly discovered bacterium.
In 2020, a research group at UiT The Arctic University of Norway in Tromsø discovered a previously unknown bacterium. Named Staphylococcus borealis (S. borealis) after the Northern Lights, the researchers investigated whether this newly discovered bacterium was a potential threat. Their findings were published in the journal Microbiology Spectrum.
33% Antibiotic Resistance
To investigate, researchers collected bacterial samples stored in freezers at several Norwegian hospitals.
The samples went as far back as 2014, and the researchers conducted new tests to see if they could identify the new bacterium in the old samples. Meanwhile, new samples arriving at the UiT lab from 2020 to 2024 were tested continuously. In total, the researchers collected and analysed 129 samples from seven Norwegian hospitals.
It turns out that S. borealis is resistant to more than three different classes of antibiotics in one-third of the cases where it was tested.
Moreover, the bacterium also appears to be highly adept at acquiring protective mechanisms from other bacterial species. This means it could potentially develop antibiotic resistance quickly, when attacked with the medicines currently available.
“We see the most resistance against the antibiotic classes fusidic acid, cephalosporins, penicillins, macrolides, and fluoroquinolones,” explains Jorunn Pauline Cavanagh, who led the work on bacterial analyses.
A Problem for the Elderly
S. borealis is a bacterium that lives on our skin, and researchers have found that it can become problematic when your immune system is weakened. This makes it particularly concerning for the elderly and for those who have had knee or hip replacements.
“This bacterium is an opportunist that can cause illness when your immune system is compromised. For example, we see that it can form what’s called biofilm around knee prostheses and cause infections that can be difficult to treat,” explains Jorunn Pauline Cavanagh.
Researchers are now working to determine which diseases this bacterium can cause. Preliminary findings suggest it may lead to urinary tract infections, as well as inflammation in areas where implants are present.
“We do know that it causes mastitis in dromedary camels. This is because we’ve published the bacterium’s genetic profile in international databases, which other researchers use to compare their own bacterial findings. So, more possibilities may emerge,” says Cavanagh.
Both high and low-middle income countries have stepped up their efforts to reduce antibiotic resistance
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash
National-level policies can reduce the impact of antibiotic resistance across diverse countries, according to a study published April 30, 2025 in the open-access journal PLOS Global Public Health by Peter Søgaard Jørgensen from Stockholm University and the Royal Swedish Academy of Sciences, Sweden, and colleagues.
Antibiotic resistance is a major public health concern, contributing to 1.27 million deaths per year. In 2016, countries around the world committed to developing and implementing national action plans to combat antibiotic resistance. These plans have been criticised for not being fully operationalised. Assessing their impact is challenging – change doesn’t happen overnight, not all countries report their data systematically, and the COVID-19 pandemic disrupted monitoring.
In this study, researchers used the Global Database for Tracking Antimicrobial Resistance Country Self- Assessment Survey (TrACSS) and data on antibiotic use and antibiotic resistance to evaluate the impact of national action over time in 73 countries, representing six continents across high and low-middle income countries. They looked at national trends in indicators related to antibiotic resistance, including antibiotic use, rates of antibiotic resistance, and impact of resistant infections.
By assigning each country an action index, they found that national action was consistently associated with improved indicators of antibiotic resistance. These associations persisted after controlling for factors like socioeconomic conditions, population density, and climate.
Since 2016, both high and low-middle income countries have become more ambitious with their national action plans; only one-third have decreased their efforts to reduce antibiotic resistance.
The authors noted some bias in their sample size in that high-income countries are more likely to have established monitoring systems but stressed the importance of studies like this to establishing the impact of national policies on tackling antibiotic resistance.
The authors add: “Our research shows the importance of all countries taking additional action to address antibiotic resistance. Very ambitious action will be needed to achieve reductions in resistance, but even incremental improvements will help reduce the projected increases…We were not sure that it would be possible to reduce levels of antibiotic resistance while also keeping using antibiotics to the extent that is required by modern health systems, but our research indicates that it is indeed possible.”
