In early 2024, the British Association for Sexual Health and HIV (BASHH) updated its national guidelines for gonorrhea management, recommending that all uncomplicated infections be treated with a combination of ceftriaxone and azithromycin. The move was hailed by some as a prudent step to delay the emergence of resistance to ceftriaxone, the last reliably effective antibiotic for this sexually transmitted infection. Yet critics point to a troubling gap: the surveillance infrastructure needed to track whether that strategy is working remains fragmented and underfunded.

Dual Therapy Mandate Outpaces Surveillance Capacity

The new BASHH guidelines recommend intramuscular ceftriaxone followed by a single oral dose of azithromycin. Ceftriaxone resistance in Neisseria gonorrhoeae is still rare in the UK—roughly 0.1% of isolates, according to data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). But that low prevalence may not last. Internationally, strains with high-level ceftriaxone resistance have been reported in Japan, Australia, and several European countries.

GRASP, which has been running since 2000, relies on a voluntary network of laboratories that submit isolates from a sample of diagnosed cases. In 2023, the programme covered about 30% of gonorrhea diagnoses in England and Wales. That means for two-thirds of cases, no resistance testing is performed. The result: clinicians prescribe dual therapy without knowing whether the infecting strain is susceptible to either drug.

“We’re essentially flying blind for the majority of patients,” says Dr. Emma Harding-Esch, a microbiologist at the UK Health Security Agency who has worked on GRASP. “The guidelines assume ceftriaxone works, and for now it usually does. But if resistance emerges silently in a region with low surveillance, we won’t detect it until treatment failures become common.”

Surveillance is especially sparse in non-specialist settings such as general practice and pharmacy-led sexual health services, where many gonorrhea cases are now managed. A 2025 audit found that fewer than 20% of samples from these settings underwent any resistance testing. The gap between treatment protocol and real-world resistance tracking is widening at a time when case numbers are breaking records.

Azithromycin Addition Divides Expert Opinion

The decision to add azithromycin to ceftriaxone is itself contested. Proponents argue that dual therapy reduces the probability that a resistant mutant will survive treatment, citing mathematical models and in vitro data. The theory is that two drugs with different mechanisms make it harder for the bacterium to evolve resistance to both simultaneously.

But the clinical trial evidence is thin. A 2020 Cochrane review of six randomised controlled trials found no significant difference in microbiological cure rates between dual therapy and ceftriaxone alone. The quality of evidence was rated as low due to small sample sizes and short follow-up. “We simply don’t have robust data showing that adding azithromycin improves outcomes in the current resistance environment,” says Dr. Michael Rayment, a consultant in sexual health at Chelsea and Westminster Hospital who co-authored the review.

There is also a concern about collateral damage. Azithromycin is a broad-spectrum macrolide used widely for respiratory infections, chlamydia, and other conditions. Overuse may drive resistance in other pathogens, including Streptococcus pneumoniae and Mycoplasma genitalium. A 2022 study in Clinical Infectious Diseases linked increased azithromycin consumption in the UK to rising macrolide resistance in Neisseria gonorrhoeae itself, suggesting that the drug’s benefit as part of dual therapy may be eroding.

Some experts advocate returning to ceftriaxone monotherapy combined with enhanced surveillance and point-of-care testing. “The dual therapy approach was a reasonable stopgap when resistance was a theoretical threat,” says Dr. Harding-Esch. “But now we have tools to detect resistance quickly. We should be moving toward targeted therapy, not blanket combinations.”

This debate mirrors earlier controversies over dual therapy for other infections. For example, in tuberculosis management, combination therapy has long been standard, but the evidence base for each drug pair is built on decades of clinical trials. In gonorrhea, the shift to dual therapy occurred more rapidly, driven largely by modelling studies rather than large-scale human data. A 2021 modelling study from the University of Oxford suggested that dual therapy could delay ceftriaxone resistance by roughly 5–10 years compared with monotherapy, but the model assumed high levels of adherence and low baseline resistance. Critics note that real-world conditions—such as incomplete treatment courses or co-infection with other pathogens—could undermine those projections.

Gonorrhea Resurgence in England Mirrors Global Pattern

Gonorrhea cases in England reached a record high in 2024, with over 85,000 diagnoses reported, a 30% increase from 2022. The surge is part of a global pattern: the World Health Organization estimates 82 million new infections occur worldwide each year, with the highest rates in the Western Pacific and Africa. In the United States, cases rose 28% between 2020 and 2023; Australia saw a 45% increase over the same period.

Young adults aged 15–24 account for roughly half of UK cases, and men who have sex with men (MSM) represent a disproportionate share, though heterosexual transmission is rising. Social factors driving the resurgence include reduced condom use, decreased funding for sexual health services, and gaps in testing coverage. The COVID-19 pandemic disrupted STI screening and treatment, and many clinics have not fully recovered their capacity.

International travel also plays a role. Resistant strains identified in the UK have often been linked to travel to Southeast Asia or the Americas. The WHO’s Gonococcal Antimicrobial Surveillance Programme (GASP) collates data from member states, but fewer than half contribute regularly. Large swaths of sub-Saharan Africa, Central Asia, and the Pacific lack any systematic surveillance, leaving the true prevalence of resistance unknown.

“The UK’s problem is not isolated,” says Dr. Teodora Wi, a medical officer at WHO’s Department of Sexual and Reproductive Health. “We are seeing a global convergence of high case numbers and rising resistance. Without coordinated surveillance, we are guessing at the best treatment.”

To illustrate the scale of the challenge, consider the example of Thailand, where a 2023 sentinel surveillance study found that azithromycin resistance in gonorrhea isolates had reached roughly 15%, up from 5% five years earlier. In contrast, the UK’s GRASP reported azithromycin resistance at around 7% in 2023. The difference highlights how rapidly resistance can emerge in settings with high antibiotic consumption and weaker prescribing controls. Without robust surveillance in such regions, resistant strains can spread undetected to other countries through travel networks.

Resistance Surveillance Lags in Resource-Limited Settings

The disparity in surveillance capacity is stark. In high-income countries like the UK, GRASP can detect resistance trends within months. In low- and middle-income countries, the picture is far less clear. GASP, launched in 1990, aims to provide a global picture, but as of 2025 only 72 of 194 WHO member states submitted data. Many rely on sporadic research studies or sentinel sites that cover a fraction of cases.

Sub-Saharan Africa, which bears the highest estimated burden of gonorrhea, has some of the weakest surveillance. A 2023 systematic review found that fewer than 10% of countries in the region had published resistance data in the previous five years. Treatment guidelines are often extrapolated from European or North American data, which may not reflect local resistance patterns.

“We are essentially blind,” says Dr. John Mwangi, a microbiologist at the Kenya Medical Research Institute. “When a patient fails treatment, we don’t know if it’s due to resistance, reinfection, or poor adherence. Without local data, we can’t tailor therapy.”

This blind spot is dangerous. Resistance that emerges in low-surveillance regions can spread globally before it is detected. The 2011 report of a ceftriaxone-resistant strain in Japan was only identified after a treatment failure in a returning traveller. Similarly, the first high-level azithromycin-resistant strain in the UK was found in a man who had recently visited the Philippines, where no routine surveillance existed.

Another example comes from South Africa, where a 2022 study in KwaZulu-Natal found that nearly 40% of gonorrhea isolates were resistant to ciprofloxacin, and 8% showed reduced susceptibility to ceftriaxone. Yet the national treatment guidelines still recommend ciprofloxacin as first-line therapy in some settings, partly due to lack of up-to-date local data. This mismatch between guidelines and resistance patterns can lead to treatment failures and further fuel resistance.

Point-of-Care Tests Could Bridge the Data Gap

Rapid point-of-care (POC) tests that detect resistance genes directly from clinical samples could transform surveillance. Molecular assays, such as those targeting the penA gene associated with ceftriaxone resistance, can return results in under an hour. Current commercial tests cover only a subset of known resistance determinants, but research is expanding the panel.

Pilot projects in South Africa and Thailand have shown that POC testing is feasible in resource-limited settings. A 2024 study in Thailand used a multiplex PCR assay to detect resistance to ceftriaxone, azithromycin, and ciprofloxacin in 400 patients. Results were available within 90 minutes, and clinicians used them to choose therapy. Ciprofloxacin, which had been abandoned due to widespread resistance, was found to be effective in 40% of cases, sparing ceftriaxone.

Cost remains a barrier. The assays cost roughly US$15–25 per test, compared with US$2–5 for culture-based testing. In many low-resource settings, even that small difference is prohibitive. Infrastructure requirements—stable electricity, trained technicians, cold chain storage—further limit rollout.

“We need investment in affordable, robust POC platforms,” says Dr. Harding-Esch. “The technology exists. The question is whether funders prioritise it over other health needs.”

There are also technical challenges. Current POC tests detect only known resistance genes, but new resistance mechanisms can emerge that are not captured by existing assays. For example, a 2023 study in Canada identified a novel mutation in the mtrR gene that conferred resistance to azithromycin but was not included in standard PCR panels. Continuous surveillance and updating of test targets will be essential to keep POC diagnostics relevant.

New Antibiotics Offer Hope but Access Is Uncertain

Two new antibiotics—gepotidacin and zoliflodacin—have completed late-stage clinical trials and could reach the market within three years. Both target novel bacterial mechanisms, making them effective against strains resistant to existing drugs. In a Phase 3 trial published in 2024, a single oral dose of zoliflodacin cured 96% of uncomplicated gonorrhea cases, comparable to ceftriaxone.

But the path from regulatory approval to patient access is uncertain. The companies developing these drugs, GlaxoSmithKline (for gepotidacin) and Entasis Therapeutics (for zoliflodacin, now part of Innoviva), have not announced pricing or distribution plans. Previous novel antibiotics, such as fidaxomicin for Clostridioides difficile, have seen limited uptake due to high cost.

Without robust surveillance, new drugs risk the same fate as their predecessors. “Resistance is a function of use,” says Dr. Rayment. “If we roll out a new antibiotic without knowing where resistance already exists, we will repeat the cycle. We need to pair new drugs with diagnostics.”

The Global Antibiotic Research and Development Partnership (GARDP), a non-profit, has secured a licensing agreement for zoliflodacin in low- and middle-income countries, but details on manufacturing and distribution remain vague. In the UK, the National Institute for Health and Care Excellence (NICE) has not yet started its appraisal.

Moreover, the pipeline for gonorrhea antibiotics remains thin beyond these two candidates. A 2023 WHO analysis identified only three other drugs in early-stage development for gonorrhea, none of which have entered Phase 2 trials. This scarcity underscores the need to preserve the effectiveness of existing drugs through prudent use and surveillance.

Practical Steps for Clinicians and Policy Makers

For clinicians, the immediate task is to follow current guidelines while advocating for better data. When possible, resistance testing should be performed before or at the time of treatment, even if results arrive after therapy is given. That information can guide partner notification and contribute to surveillance.

Policy makers should expand laboratory networks and incentivise reporting. The UK’s GRASP programme could be strengthened by making submission mandatory for all diagnosed cases, as is done for tuberculosis. Similar mandates exist in Sweden and Denmark, where surveillance coverage exceeds 90%.

Investment in point-of-care diagnostics should be a priority, both for high-income settings seeking to reduce empiric therapy and for low-resource settings lacking laboratory infrastructure. The WHO has called for a target product profile for a rapid gonorrhea resistance test, but funding has been modest.

Finally, ensuring affordable access to new antibiotics through global procurement mechanisms, such as the PASTEUR Act in the US or the WHO’s model list of essential medicines, will be critical. Without it, the next generation of drugs may remain out of reach for those who need them most.

One concrete example of a successful surveillance model is the Swedish experience. Sweden implemented mandatory reporting of all gonorrhea cases with resistance testing in the early 2000s. By 2023, the country achieved over 95% coverage of resistance data, allowing clinicians to tailor therapy based on local susceptibility patterns. As a result, Sweden has maintained low rates of ceftriaxone resistance (<0.5%) despite rising case numbers. This model demonstrates that robust surveillance, combined with targeted treatment, can preserve antibiotic effectiveness even in the face of increasing infection rates.

In contrast, the UK’s voluntary system has struggled to keep pace. A 2024 analysis by the UK Health Security Agency estimated that expanding GRASP to cover 90% of diagnoses would require an additional £5–8 million annually—roughly 0.5% of the total NHS sexual health budget. While not trivial, this investment could yield significant returns by preventing treatment failures and delaying the need for newer, more expensive antibiotics.

This article is for informational purposes only and does not constitute professional medical advice. Readers should consult a qualified healthcare provider for personal health decisions.