In 2025, the UK Health Security Agency (UKHSA) reported nearly 85,000 gonorrhea diagnoses, the highest annual total since records began. Rates are highest among young adults aged 15–24, and resistance to ceftriaxone—the last-line antibiotic—is emerging, with treatment failures documented in England since 2023. This article explains the biology behind resistance, the surveillance gaps that allow it to spread, and the vaccine that could have prevented much of this surge.

A record that signals failure

The 2025 figure of roughly 85,000 cases represents a 15% increase from 2024 and a doubling over the past decade. Gonorrhea is now the second most common bacterial sexually transmitted infection in the UK, after chlamydia. The UKHSA estimates that if current trends continue, annual cases could reach 200,000 by 2030 without additional interventions.

Rates are highest among young adults aged 15–24, particularly in London and other urban areas. Men who have sex with men account for a disproportionate share, but heterosexual transmission is also rising. The infection is often asymptomatic, especially in women, which means many cases go undiagnosed and untreated, fueling further spread.

Resistance to ceftriaxone, the current first-line treatment, is the most worrying development. In 2023, UKHSA confirmed the first ceftriaxone-resistant gonorrhea cases in England that were not acquired abroad. Since then, sporadic treatment failures have been reported, and surveillance data show a creeping increase in the minimum inhibitory concentration (MIC) of ceftriaxone among isolates from London clinics.

The WHO lists gonorrhea as a high-priority pathogen for which new antibiotics are urgently needed. The bacterium Neisseria gonorrhoeae has a remarkable ability to develop resistance, having already defeated sulfonamides, penicillins, tetracyclines, and fluoroquinolones. Ceftriaxone is the last remaining monotherapy that reliably cures uncomplicated infections.

How Neisseria gonorrhoeae outwits our drugs

Neisseria gonorrhoeae is a master of genetic adaptation. It acquires resistance genes through horizontal transfer from other bacteria, including commensal Neisseria species that live harmlessly in the throat. Mosaic penA alleles, which encode a modified penicillin-binding protein, reduce ceftriaxone binding and are the primary mechanism of resistance to extended-spectrum cephalosporins.

Efflux pumps, such as the MtrCDE system, actively expel multiple antibiotic classes from the bacterial cell, reducing intracellular drug concentrations. Mutations in the promoter region of the mtrR gene upregulate these pumps, conferring resistance to macrolides like azithromycin and, to a lesser extent, cephalosporins. Porin mutations also reduce drug permeability.

No new class of antibiotics for gonorrhea has been introduced in decades. The last novel class, the fluoroquinolones, entered clinical use in the 1980s and are now largely ineffective due to widespread resistance. The pipeline for new drugs is thin, with only two candidates—zoliflodacin and gepotidacin—in late-stage clinical trials as of mid-2026.

The WHO has classified gonorrhea as a high-priority pathogen for antibiotic research, but drug development is slow and expensive. The bacterium's ability to rapidly evolve resistance means that even new drugs may have a limited shelf life. Without careful stewardship, the same cycle of resistance will repeat.

The surveillance gap in sexual health clinics

Diagnosing gonorrhea typically involves nucleic acid amplification tests (NAATs), which are rapid and sensitive but do not provide information about antibiotic susceptibility. Culture testing, which grows the bacterium in the lab, is needed to perform antimicrobial susceptibility testing (AST) and detect emerging resistance. However, culture requires specialised media, trained staff, and viable organisms, making it more expensive and slower.

As of late 2024, only about half of sexual health clinics in England routinely perform extended AST on gonorrhea isolates. Many rely on NAATs alone, which means resistance can go undetected until treatment failures occur. The UKHSA recommends that all positive cultures be tested for ceftriaxone and azithromycin susceptibility, but compliance is uneven.

Contact tracing is another weak link. Patients diagnosed with gonorrhea are advised to notify recent partners, but many do not, and clinic resources for partner notification are stretched. Underfunded sexual health services in some regions have long waiting times, which can delay treatment and increase the risk of onward transmission.

The surveillance gap means that resistance trends are often identified only after they have become established. For example, azithromycin resistance was already above 10% nationally by the time routine surveillance detected the rise. Earlier recognition might have allowed for targeted interventions, such as switching to alternative regimens in high-prevalence areas.

When dual therapy becomes no therapy

The current UK guideline for uncomplicated gonorrhea is ceftriaxone 1 g intramuscularly plus azithromycin 1 g orally as a single dose. This dual therapy was introduced in 2011 to delay the emergence of resistance to either drug. However, azithromycin resistance now exceeds 10% nationally, and in some regions, it approaches 20%. When the bacterium is resistant to azithromycin, dual therapy effectively becomes ceftriaxone alone.

Ceftriaxone MIC creep has been detected in isolates from London, with a growing proportion showing MICs at the upper end of the susceptible range. While these isolates are still classified as susceptible, the margin for error is shrinking. If MICs continue to rise, treatment failures will become more common, and the dose of ceftriaxone may need to be increased—but there is no evidence that higher doses are safe or effective.

For patients who fail ceftriaxone, there are no validated oral alternatives. Retreating requires intravenous antibiotics such as ertapenem or gentamicin, which are less convenient, more expensive, and carry greater side effects. Gentamicin, for example, has nephrotoxicity and ototoxicity risks, and its efficacy for pharyngeal gonorrhea is limited.

Pharyngeal gonorrhea is particularly difficult to treat because drug concentrations at that site are lower, and the bacterium can persist asymptomatically. Test of cure is recommended for pharyngeal infections, but many clinics do not routinely perform it. Missed pharyngeal infections can serve as a reservoir for resistance.

The vaccine that could have been

Observational studies in New Zealand, Canada, and the United States have shown that the meningococcal B vaccine (4CMenB, marketed as Bexsero) offers around 40% protection against gonorrhea. The effect is thought to be due to cross-reactive antibodies against surface proteins shared between Neisseria meningitidis and Neisseria gonorrhoeae.

In 2024, the UK Joint Committee on Vaccination and Immunisation (JCVI) declined to recommend routine adolescent vaccination with 4CMenB for gonorrhea prevention, citing uncertainties about the duration of protection and cost-effectiveness. However, subsequent modeling by UKHSA suggested that vaccinating adolescents would be cost-effective if protection lasted at least five years, and could prevent tens of thousands of cases over a decade.

Critics argue that the JCVI's decision was overly cautious. Australia has already implemented targeted 4CMenB vaccination for men who have sex with men in some states, and early data suggest a reduction in gonorrhea incidence. The delay in the UK means that while cases climb, an effective intervention remains unused.

A dedicated gonorrhea vaccine is still years away, but 4CMenB is available and licensed. The JCVI has said it will reconsider the evidence in 2027, but each year of delay allows the epidemic to grow and resistance to spread. The vaccine is not perfect—40% efficacy means many infections would still occur—but it could substantially reduce the burden.

What primary care can do now

General practitioners and sexual health clinicians are on the front line. When a patient presents with symptoms of urethritis or cervicitis, the recommended approach is to test with NAAT plus a culture swab for resistance profiling. Empiric treatment with ceftriaxone and azithromycin should be given immediately, but the culture result can guide follow-up if resistance is detected.

Test of cure is essential for pharyngeal gonorrhea and for any case where there is a concern about resistance. The UKHSA recommends a test of cure 2 weeks after treatment, using culture or NAAT depending on the site. If the test is positive, the isolate should be sent for susceptibility testing, and the case should be reported to UKHSA within 24 hours.

Partner notification should be offered to all patients, either through patient referral (the patient informs partners) or provider referral (the clinic contacts partners directly). In many clinics, this is done by health advisers. However, resources are limited, and some patients are lost to follow-up. Using text message reminders or online partner notification tools can improve completion rates.

Prescribing should follow local resistance data where available. Some regions have published antibiograms showing the proportion of isolates resistant to azithromycin or with elevated ceftriaxone MICs. In areas with high azithromycin resistance, some experts suggest using ceftriaxone alone or adding a different second agent, though this is not yet guideline-endorsed.

The cost of waiting for new drugs

Two new oral antibiotics are in late-stage clinical trials for uncomplicated gonorrhea: zoliflodacin (a spiropyrimidinetrione) and gepotidacin (a triazaacenaphthylene). Both have novel mechanisms of action and have shown good efficacy in Phase II trials. If approved, they would be the first new oral antibiotics for gonorrhea in 30 years.

However, history suggests that resistance will eventually emerge. The bacterium has already shown it can develop resistance to both drugs in laboratory settings. Stewardship will be critical: these drugs should be reserved for cases where standard therapy fails or resistance is documented, not used as first-line agents. Without strict stewardship, their lifespan could be short.

Vaccination offers a longer-term solution. Even a modestly effective vaccine, like 4CMenB, could slow the epidemic and reduce the selective pressure for resistance. The cost of waiting is measured in rising cases, more treatment failures, and the eventual possibility of untreatable gonorrhea—a scenario that the WHO has warned could lead to increases in pelvic inflammatory disease, ectopic pregnancy, and infertility.

UKHSA estimates that without new interventions, annual cases could reach 200,000 by 2030. The current trajectory is unsustainable. The tools to change it exist—a vaccine, new drugs, better surveillance—but they need to be deployed now, not when the crisis is undeniable.

Trade-offs in surveillance and treatment

Decisions about where to invest resources involve trade-offs. For example, expanding routine culture testing in sexual health clinics would improve resistance surveillance, but it would also require additional funding for laboratory capacity and staff training. Some clinics have argued that the cost of universal AST is not justified given the current low prevalence of ceftriaxone resistance. However, this argument overlooks the fact that resistance can spread silently before it becomes clinically apparent. In the Netherlands, a similar debate occurred in the early 2010s regarding azithromycin resistance; by the time routine surveillance was expanded, resistance had already reached 7% nationally. The UK risks repeating this pattern with ceftriaxone.

Another trade-off involves the choice between dual therapy and monotherapy. Dual therapy with ceftriaxone plus azithromycin was intended to reduce the risk of resistance emerging to either drug. However, as azithromycin resistance rises, the benefit of the combination diminishes. Some experts have proposed switching to ceftriaxone monotherapy, arguing that it would reduce antibiotic exposure and potentially slow the development of macrolide resistance in other pathogens. Others counter that monotherapy would accelerate ceftriaxone resistance, since the bacterium would be exposed to only one drug. The UKHSA has not yet revised its guidelines, but the debate highlights the difficulty of balancing short-term efficacy against long-term resistance prevention.

Similarly, the decision to vaccinate adolescents with 4CMenB involves trade-offs between immediate costs and future benefits. The JCVI's cautious approach reflects the uncertainty about the duration of protection and the possibility that the vaccine might not be cost-effective if protection wanes quickly. However, modeling from UKHSA indicates that even moderate protection lasting five years would prevent a substantial number of cases. The cost of the vaccine program would be offset by savings from reduced treatment costs, fewer complications, and less transmission. Australia's early experience suggests that targeted vaccination can be implemented without disrupting existing immunization schedules. The UK's delay may reflect a preference for waiting for more data, but each year of delay incurs a public health cost.

Finally, there is a trade-off between investing in new drug development and strengthening existing public health measures. New drugs like zoliflodacin and gepotidacin are promising, but they are unlikely to be available for routine use before 2028 or later. In the meantime, improving surveillance, contact tracing, and test-of-cure rates could have an immediate impact. For example, a study in London found that enhanced partner notification using text message reminders increased the proportion of partners treated from 50% to 70%. Such interventions are relatively inexpensive and could reduce the reproductive number of the infection. The challenge is that sexual health services are already underfunded, and many clinics are struggling to maintain basic services. Without additional investment, even the best evidence-based strategies will remain underutilized.

This article is for informational purposes only and does not constitute medical advice. Patients with symptoms should consult a healthcare professional.