The results, published in The Lancet, position the drug, zoliflodacin, as a potential new treatment option amid the growing prevalence of drug-resistant strains of Neisseria gonorrhoeae, the bacterium responsible for gonorrhoea.
Gonorrhoea is one of the most common sexually transmitted infections worldwide. Over recent decades, the causative bacterium has developed resistance to many standard treatments. Zoliflodacin still needs to undergo regulatory review before it can be introduced into routine clinical practice. Until then, the current standard treatments, which are administered by intramuscular injection, remain the recommended therapy.
What is gonorrhoea and why is it a concern?
Gonorrhoea is a common sexually transmitted infection (STI) that has become an increasing public health concern because the bacterium that causes it has developed resistance to various antibiotics. The infection is primarily transmitted through unprotected sexual activity with an infected individual.
The infection can affect the genital tract, rectum and throat.
In addition, if not treated appropriately, it can spread and lead to sepsis. In some cases, it causes discomfort during urination, discharge or genital and rectal pain, but it may also go unnoticed. This facilitates transmission without the infected person being aware of it.
The main cause for concern is antimicrobial resistance: the phenomenon whereby bacteria adapt to medications that previously eliminated them, making them ineffective. In the case of gonorrhoea, therapeutic options have been progressively reduced over the years.
Multidrug-resistant gonorrhoea refers to strains of the bacterium resistant to several antibiotics. The WHO has warned that, if this trend continues, gonorrhoea could become very difficult to treat with the drugs currently available. Between 2022 and 2024, resistance to the two antibiotics most commonly used as standard treatment increased from approximately 2 in every 100 cases to 11 in every 100 cases. This increase highlights the need to develop new treatments.
What is zoliflodacin and how does it work?
Zoliflodacin is a novel single-dose oral antibiotic developed for the treatment of gonorrhoea via a mechanism different from that of currently available antibiotics. It acts by inhibiting an essential process that allows the bacteria to replicate.
The drug interferes with an enzyme required by the bacterium to replicate and organise its DNA. When this process is disrupted, the bacterium loses its ability to replicate, allowing the infection to be cleared.
This mechanism is particularly significant because zoliflodacin targets a different bacterial site to that of other antibiotics. This may help preserve its activity against strains that have already developed resistance to existing treatments.
What has the clinical trial demonstrated?
The phase III clinical trial demonstrated that a single oral dose of zoliflodacin achieves cure rates exceeding 90% in cases of uncomplicated urogenital gonorrhoea, comparable to that obtained with the current standard treatment, which is based on a combination of injectable and oral antibiotics.
The study enrolled nearly 930 participants from five countries—the United States, South Africa, Thailand, Belgium and the Netherlands—and was conducted across 17 outpatient clinics. These findings position zoliflodacin as a promising candidate for expanding the therapeutic options available for treatment of this increasingly drug-resistant infection.
Why is the fact that it is an oral treatment relevant?
The fact that zoliflodacin is a single-dose oral treatment may provide rapid, complete management of gonorrhoea. In sexually transmitted infections, early treatment is essential both to achieve a cure and reduce the risk of onward transmission.
The current recommended treatment for gonorrhoea requires intramuscular administration. An oral alternative could simplify treatment delivery, provided that its efficacy, safety and appropriate use are confirmed.
Antibiotics should be used only when clinically indicated and in accordance with the regimen prescribed by healthcare professionals. Appropriate antibiotic use helps preserve their effectiveness and reduces the risk of resistance.
What complications can gonorrhoea cause if left untreated?
Gonorrhoea can lead to significant complications if not diagnosed and treated appropriately. In people with a uterus, the infection may contribute to the development of pelvic inflammatory disease (PID), infertility and ectopic pregnancy, in which the embryo implants outside the uterus.
The infection can also affect the rectum and throat and, in some cases, can progress to more severe or disseminated forms of the disease. In addition, gonorrhoea increases the risk of both acquiring and transmitting HIV.
For these reasons, you should seek medical help when compatible symptoms are present and undergo testing if there is a potential risk of exposure. Sexual partners should also be treated when indicated. Early diagnosis and treatment help prevent complications and reduce transmission.
Why is this development important for public health?
In the context of rising antimicrobial resistance, the availability of new therapeutic agents is a public health priority. The WHO has set a target of substantially reducing gonorrhoea infections before 2030. Achieving this goal will require not only new treatment options, but also effective prevention strategies, early diagnosis, antimicrobial resistance surveillance and the prudent use of antibiotics.
Zoliflodacin could become part of this response if available evidence continues to be favourable and regulatory authorities approve its use.
How can gonorrhoea be prevented and when should medical advice be sought?
Reducing the risk of transmission during sexual activity and undergoing testing following potential exposure are the main preventive measures. The use of condoms and other barrier methods reduces the risk of STI.
Testing is recommended when symptoms occur, a sexual partner has been diagnosed with an STI or following potential exposure. In many cases, gonorrhoea may be asymptomatic, yet transmission can still occur.
When an infection is confirmed, it is important to follow the prescribed treatment regimen and assess sexual partners when appropriate to prevent reinfection.
What must be done before it can be used in clinical practice?
Zoliflodacin is still undergoing the regulatory review process. Although clinical trial results are favourable, the relevant authorities must evaluate its efficacy, safety and conditions of use before approval. The drug is not yet widely available, and current recommended treatments remain the standard of care.
The main message is that gonorrhoea is a common infection which can cause complications and so must be diagnosed and treated appropriately. New antibiotics are a necessary tool, but prevention, early diagnosis and the responsible use of treatments are essential.
INFORMATION DOCUMENTED BY:
Dr Irene Fuertes, Department of Dermatology, Hospital Clinic Barcelona.
