The bacteria responsible for gonorrhea,
Neisseria gonorrhoeaeis resistant to almost all antibiotics and has forced doctors to rely almost exclusively on an injection of ceftriaxone. Faced with this “super-gonorrhea”, some experts feared the reappearance of infections that were impossible to treat.
Friday, December 12, the American drug agency, the Food and Drug Administration (FDA), approved two
new antibiotics for gonorrheaboth orally: Nuzolvence (zoliflodacin), in a single dose to be dissolved in water, and Blujepa
(gepotidacin), tablets. These are the first treatments in a new class for gonorrhea in more than thirty years and they directly aim to combat drug resistance, with a major advantage: no need for needles.
Gonorrhea increasingly resistant to antibiotics
In 2020, the World Health Organization estimated that gonorrhea caused 82.4 million new infections per year among 15-49 year olds worldwide. In the United States, more than 600,000 cases were reported in 2023, and reports of chlamydia, gonorrhea and syphilis have jumped about 90% since 2004. In France, data published by Santé publique France for the period 2014 to 2023 show a continued increase in diagnoses of chlamydia and of gonorrheastabilization of syphilis.
Without treatment, this STI, caricatured under the name “hot piss”, can cause pelvic inflammatory disease, chronic pain, pregnancy complications and infertility, without any vaccine existing.
Injectable ceftriaxone remained the only recommended treatment for years, while N. gonorrhoeae has accumulated resistance to many families of antibiotics. “These approvals mark an important milestone for treatment options for patients with uncomplicated urogenital gonorrhea“, said Adam Sherwat, head of infectious diseases at the FDA’s Center for Drug Evaluation and Research. For Peter Kim, director of the anti-infectives division, “The availability of additional treatment options is particularly important given the global increase in gonococcal drug resistance“.
Nuzolvence and Blujepa: how these oral treatments work
Nuzolvence contains zoliflodacin, a first-in-class antibiotic that targets a specific subunit of bacterial DNA gyrase, different from that targeted by fluoroquinolones. In a phase 3 trial conducted in 930 patients in several countries, a single dose of 3 g cured approximately 91% of urogenital infections, compared to 96% with the combination of injectable ceftriaxone plus azithromycin. The most common side effects were headache, dizziness, diarrhea or transient white blood cell abnormalities.
Blujepa is based on gepotidacin, a new class antibiotic which blocks bacterial DNA replication. It is taken in two oral doses of 3,000 mg spaced 10 to 12 hours apart, in patients 12 years of age and older weighing at least 45 kg and having few or no alternatives. In the EAGLE-1 trial, approximately 93% of patients were cured, a rate similar to standard treatment, with mostly mild to moderate digestive upset.
A hope against the resistance, but a long-distance race
For field caregivers, these oral treatments also change the logistics. No more need to bring each patient into the office for an injection, which can facilitate care in overloaded clinics or remote areas. The head of the Global Antibiotic Research and Development Partnership (GARDP), Dr Manica Balasegaram, sums up the issue: “These are urgently needed medications for a disease that is spiraling out of control and much more difficult to treat.” he explained to CNN.
The abuse of antibiotics also fuels resistance, hence the choice to reserve these new drugs for gonorrhea only. In a comment published in The LancetMagnus Unemo and Teodora Wi judge that “preclinical and clinical development of additional treatments for gonorrhea remains important” because “challenges for gonorrhea to remain a treatable infection will continue“.
These new drugs are not a definitive victory, but a crucial step in keeping gonorrhea among the still treatable infections.