According to WHO estimates, 82 million people contract gonorrhea annually. For this sexually transmitted infection, essentially only one antibiotic has reliably worked for roughly four decades: Ceftriaxone, administered as an injection. In December 2025, the FDA approved the first new oral antibiotics in decades, finally creating genuine therapeutic alternatives.
Resistance to the last standard treatment is rising
Gonorrhea is transmitted through the bacterium Neisseria gonorrhoeae and progresses asymptomatically in many infected individuals. Untreated infection can lead to infertility, fallopian tube inflammation, and increased HIV transmission risk. The WHO counts gonorrhea among the four most common sexually transmitted infections globally, collectively responsible for over one million new infections daily.
The acute problem is resistance development. The WHO released data in November 2025 from its global surveillance program EGASP: between 2022 and 2024, worldwide Ceftriaxone resistance rates climbed from 0.8 to 5 percent. Against Cefixime, a related drug, resistance jumped from 1.7 to 11 percent. In Cambodia, already 15.4 percent of tested gonococci are ceftriaxone-resistant; in Vietnam, 32.4 percent. Against Ciprofloxacin, a fluoroquinolone formerly used as alternative therapy, 95 percent of strains worldwide are resistant.
Gonorrhea has defeated every antibiotic medicine has deployed: penicillin failed in the 1970s, tetracyclines in the 1980s, fluoroquinolones in the 2000s. Ceftriaxone was the last remaining therapy of choice.
How the two new drugs work
On December 12, 2025, the FDA approved Zoliflodacin (trade name Nuzolvence); one day earlier, Gepotidacin (Blujepa). Both are oral and can replace the previous injection.
Zoliflodacin is the first representative of a new antibiotic class called spiropyrimidinetriones. The drug blocks bacterial DNA gyrase at a different binding site than all previous antibiotics. Because it works at an entirely different attack point than fluoroquinolones, there is no cross-resistance to drugs that have already failed as gonorrhea treatment. In the phase-3 study pivotal for approval, involving 930 patients, 91 percent of those receiving Zoliflodacin as a single dose were microbiologically cured, compared to 96 percent in the group receiving the prior standard of Ceftriaxone plus Azithromycin. Zoliflodacin was developed by Entasis Therapeutics in collaboration with the nonprofit Global Antibiotic Research and Development Partnership (GARDP), which aims for availability in low-income countries.
Gepotidacin from GlaxoSmithKline also targets bacterial DNA machinery but simultaneously inhibits DNA gyrase and topoisomerase IV. In the EAGLE-1 study involving 628 patients, Gepotidacin achieved a microbiological cure rate of 92.6 percent compared to 91.2 percent for comparative therapy. The FDA applied a restricted label to Gepotidacin: it is intended only for patients with few or no other treatment options, since clinical trial safety data are limited. Both drugs are approved for adults and adolescents age 12 and above, with market introduction planned for the second half of 2026.
In comparison: What HIV in 1996 and Hepatitis C in 2014 showed
Sexually transmitted infections were long considered therapeutically barely controllable. Two turning points show what new drugs can accomplish.
HIV: In 1996, triple antiretroviral combination therapy (HAART) transformed an almost always fatal diagnosis into a manageable chronic condition. The key was not a single medication but a combination with different attack points, preventing the virus from simultaneously evading all mechanisms. HIV-positive people on modern therapy today have nearly normal life expectancy.
Hepatitis C: Until 2014, standard interferon therapy achieved lasting cure in only roughly 50 percent of patients, took up to a year, and caused severe side effects. With direct-acting antiviral drugs (DAA) approval since 2014, cure rates climbed above 95 percent with therapy duration of eight to twelve weeks. The WHO subsequently classified Hepatitis C as curable and adopted an elimination strategy through 2030.
For gonorrhea, the concern is not yet about curing a previously incurable disease but preventing the emergence of pan-resistant strains. Treatment failure multiplies as long as undetected infections circulate in populations.
Three conditions for global impact
FDA approval initially applies to the United States. For countries with highest resistance rates, primarily Southeast Asia and parts of Africa, real-world benefit remains to be determined.
First, EMA and national authorities in high-burden countries must promptly review and approve the new drugs. Whether Nuzolvence or Blujepa receive PRIME status enabling accelerated EMA review is unknown.
Second, pricing determines accessibility. GARDP explicitly built low-income country availability into Zoliflodacin licensing agreements. Whether GlaxoSmithKline establishes similar access arrangements for Gepotidacin remains open.
Third, gonorrhea diagnostics must expand. Resistance surveillance requires laboratories and monitoring systems. The WHO's EGASP network currently spans only 12 countries across five regions. In countries without comprehensive STI diagnostics, resistant strains spread before detection.