At any given time, one in five people in the US has a sexually transmitted infection (STI), translating to more than 68 million infections.¹ These infections cost billions in healthcare expenses each year. Even more alarming, over 48% of all new STIs in this country affect those between ages 15 and 24.^{1, 2}  The eight most common STIs tracked by the US Centers for Disease Control and Prevention (CDC) are chlamydia, gonorrhea (GC), syphilis, trichomoniasis, human papilloma virus (HPV), herpes simplex virus type-2 (HSV-2), human immunodeficiency virus (HIV), and hepatitis B virus (HBV).¹ These STIs, including HIV, can be treated, and most can be cured with appropriate and timely antibiotics.³

Antibiotic-resistant Neisseria gonorrhoeae (gonorrhea) has emerged as a critical global public health threat. Gonorrhea is the second most reported bacterial STI in the United States, with an estimated 600,000 new infections in 2023.^{4, 5} Alarmingly, nearly half of these infections are resistant to at least one antibiotic, and the incidence of gonorrhea increased by more than 40% between 2017 and 2021.⁵

Current treatment options are extremely limited; ceftriaxone remains the sole therapy recommended by the CDC. Unfortunately, resistance to this last-line drug has been reported globally and in the US.  To address this, the CDC and World Health Organization (WHO) have strengthened surveillance programs to track resistance and inform treatment guidelines. ^{5, 6, 7}  Research is focused on developing new antimicrobials and a preventive vaccine – the most sustainable solution.  Immediate priorities include rapid detection, contact tracing, antimicrobial stewardship, and international collaboration to curb the spread of extensively drug-resistant strains.

Failure to act could lead to untreatable gonorrhea, resulting in severe reproductive health complications, increased HIV transmission, and significant healthcare costs.  Coordinated action among clinicians, public health authorities, and researchers is essential to contain this escalating threat.

The Threat

In 2024, the CDC reported 543,409 new cases of gonorrhea in the US, a 20% decrease from 2020 but still higher than a decade ago. N. gonorrhoeae is the second most reported bacterial STI in the US, according to the CDC. Around half of these infections are resistant to at least one antibiotic.⁴ From 2015 to 2024, the total incidence of N. gonorrhoeae increased by over 29%; the incidence for men increased by 45.3%, and for women by 8.9% (Figure 1).⁵

Figure 1. Reported gonorrhea rates per 100,000 population in the United States by sex from 2015–2024. Reported cases increased through 2021 before declining in subsequent years, although rates remain above 2015 levels. Throughout the period, men experienced higher reported infection rates than women. 2024 data are provisional as of August 14, 2025. Source: CDC STI Surveillance.

Figure 2. Reported gonorrhea rates per 100,000 population by age group and sex in the United States in 2023. The highest reported rates occurred among adults aged 20–24 years for both men and women, with rates remaining elevated through ages 25–34. Overall, men experienced higher reported rates than women across most age groups. Source: 2023 CDC STI Surveillance Report.

As shown in Figure 2, the reported rate of gonorrhea was higher among men (228.3 per 100,000) than among women (130.7 per 100,000); this was true in all age categories.  Men aged 20 to 24 years had the highest reported rate of cases of gonorrhea at 691.1 per 100,000, followed by men aged 25 to 29 years, and men aged 30 to 34 years (with 671.2 per 100,000 and 585.8 per 100,000, respectively). Among women, those aged 20 to 24 also had the highest rate of reported cases of gonorrhea at 610.5 per 100,000, followed by women aged 15 to 19, and women aged 25 to 29 years (with 476.7 per 100,000 and 353.8 per 100,000, respectively).⁶

Worldwide, the numbers are even more troubling. According to estimates from the WHO, 2020 saw an estimated 82.4M new cases among people ages 15 to 49 around the world. Western Pacific and African regions had the most infections observed.⁷ There are mainly five reasons for the increase observed in gonococcal infections and resistance:

• Unrestricted antimicrobial access
• Inappropriate antibiotic use
• Suboptimal drug quality
• Genetic mutations
• Extra-genital infections due to N. gonorrhoeae interacting with and exchanging genetic material with other organisms present in these parts of the body⁸

The Disease

Gonorrhea is a common sexually transmitted disease that can cause infections of the genitals, rectum, and throat. It can be treated and cured, but this organism readily becomes resistant to antibiotics.⁴ It is one of the more troubling STIs, because many people that are infected do not have symptoms and thus can spread it unknowingly.⁷ Gonorrhea can pose greater risks for women. If untreated, gonorrhea can cause serious and permanent reproductive problems such as ectopic pregnancy, maternal death, first trimester miscarriage, a five-fold increase of HIV transmission, infertility, and severe neonatal eye infections that may lead to blindness.  Untreated infections in both men and women can also result in cardiovascular and neurological issues.^{9, 10}

The Problem

In 2013, the CDC classified antibiotic-resistant N. gonorrhoeae as an Urgent Threat;¹⁰ this organism was added to the next list in 2019 as well.  This escalation of threat status was due to the continued increase in antibiotic resistance observed with N. gonorrhoeae, as total infections and antibiotic-resistant cases rose dramatically over the preceding decade.  Over time the options available to clinicians to treat gonorrheal infections have become more limited because of the worldwide spread of resistance to all available antimicrobial agents, namely penicillins, narrow spectrum cephalosporins, tetracyclines, macrolides, and fluoroquinolones.⁹ Currently, ceftriaxone is the only treatment option that is recommended by the CDC. Resistance to this agent has been reported as well but has yet to become widespread (Figure 3).¹⁰ Ceftriaxone and another extended-spectrum cephalosporin (ESC), cefixime, are powerful antibiotics used clinically to treat a variety of infections.  As with other bacteria, N. gonorrhoeae has developed several ways to become resistant to ESCs: by altering the bacterial target of these drugs, by overexpressing a membrane pump that keeps these drugs out of the cells, or by making changes in a membrane protein that blocks the drugs from entering the cells.  The first ceftriaxone-resistant isolate was identified in Japan in 2011, where there was only limited monitoring of gonococcal antimicrobial resistance, underscoring the urgent need for global surveillance standards.¹¹

Figure 3. Trends in antimicrobial resistance among Neisseria gonorrhoeae isolates in the United States from 2000–2016. Resistance to several previously recommended antibiotics increased over time, leading to successive changes in treatment guidelines. Ceftriaxone remained the only recommended first-line treatment during this period because resistance remained rare. Source: CDC Antibiotic Resistance Threats.

In 2023, a novel strain of antibiotic-resistant gonorrhea was identified in two patients in Massachusetts that was resistant to five classes of antibiotics, the first time such a strain was identified in the US.¹² The two apparently unrelated cases were both cured with ceftriaxone, the sole treatment left for gonorrhea.  Although resistant N. gonorrhoeae isolates have been identified in the UK and Asia-Pacific countries, these are the first reported in the US.¹² In another worrisome case, a 50-year-old male patient in Europe returning from a trip to Cambodia had an infection with a strain of N. gonorrhoeae that was identified as extensively drug-resistant (XDR), meaning it was only susceptible to one or two antibiotic classes.  Despite courses of ceftriaxone and azithromycin for two weeks, the patient remained infected; finally, after a course of amoxicillin-clavulanic acid treatment the patient tested negative for N. gonorrhoeae.¹³ These cases underscore the urgent need for new agents to treat this contagious disease.  There is some recent good news, as the US Food and Drug Administration (FDA) has approved two new oral antibiotics to treat gonorrhea: zoliflodacin (Nuzolvence) and gepotidacin (Blujepa).  Both treatments were found to be as effective as the standard of care treatment (ceftriaxone injection plus an azithromycin pill).¹⁴

The Response

To help combat the troubling increase in STIs in the last few years, the CDC has put together a network of selected state, county and city health department sentinel sites to follow rates of several STIs and determine the percent compliance within each jurisdiction.  The data gathered by this Sexually Transmitted Disease Surveillance Network (SSuN) can also help clinicians and researchers detect emerging antibiotic resistance, and how well communities are adhering to CDC treatment guidelines.¹⁵

The WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) was started in 1990 as a global collaborative network to monitor gonococcal antimicrobial resistance across the globe.  This enormous effort continues today, with the WHO issuing reports on the data collected in what is now called the Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).¹⁶ The first EGASP report was issued in 2023, and covered surveillance from 2015 to 2022 in Cambodia, the Philippines, Thailand, and Uganda. This was followed up in 2024 with an expansion of their surveillance efforts, which added Indonesia, Malawi, South Africa, Viet Nam, and Zimbabwe to the initial four countries.  Isolates of N. gonorrhoeae resistant to the last options for first-line empirical treatment (ceftriaxone alone or ceftriaxone plus azithromycin) were reported in both documents, especially in Viet Nam and Cambodia. EGASP protocols continue to be implemented in sentinel sites, helping to fortify STI surveillance, epidemiology, antimicrobial resistance reporting, and standardization of sample collection.¹⁶ These data are also useful in informing updates to treatment guidelines.

As of December 2024, the program had been adopted in 13 countries across the globe; including the ones noted above, Cote d’Ivoire, India, Qatar, and Brazil have been added, resulting in 46 sentinel clinics and 2,429 positive N. gonorrhoeae isolates.¹⁶

The Future

New antimicrobials are of course needed, and the urgent hope is for a vaccine; both are subjects of research at several institutions.  Other actions, including early detection and treatment, contact tracing, antimicrobial stewardship, surveillance of infection, monitoring of antimicrobial resistance and gonorrhea treatment failures and diagnostics.¹⁷

Partner with Microbiologics to Advance Anti-Infective Discovery

The growing threat of antibiotic-resistant Neisseria gonorrhoeae underscores the urgent need for innovative antimicrobial therapies. Microbiologics is a trusted CRO partner supporting antibacterial and antifungal drug development with customized in vitro microbiology assays, clinically relevant pathogen collections, and scientific expertise spanning discovery through regulatory submission. Whether you’re screening novel compounds, evaluating resistance mechanisms, or generating data for an IND, our team can help accelerate your program with confidence.

Resources:

1. Forbes. 20% of Americans Have an STI, But It’s Not Necessarily Who You Think. January 25, 2024. https://www.forbes.com/
2. The Global Statistics. Sexually Transmitted Diseases Statistics in the U.S. 2025. https://www.theglobalstatistics.com/std-statistics/
3. Centers for Disease Control and Prevention (CDC). Know the Facts About STIs. https://www.cdc.gov/sti-awareness/gyt/know-the-facts.html
4. Centers for Disease Control and Prevention (CDC). Drug-Resistant Gonorrhea. https://www.cdc.gov/gonorrhea/hcp/drug-resistant/index.html
5. Centers for Disease Control and Prevention (CDC). Sexually Transmitted Infections Surveillance. https://www.cdc.gov/sti-statistics/annual/index.html
6. Centers for Disease Control and Prevention (CDC). Sexually Transmitted Infections Surveillance Report 2023. https://www.cdc.gov/sti-statistics/media/pdfs/2025/09/2023_STI_Surveillance_Report_FINAL_508.pdf
7. World Health Organization (WHO). Gonorrhoea (Neisseria gonorrhoeae Infection). https://www.who.int/news-room/fact-sheets/detail/gonorrhoea-(neisseria-gonorrhoeae-infection)
8. World Health Organization (WHO). Multi-Drug Resistant Gonorrhoea. https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea
9. Centers for Disease Control and Prevention (CDC). About Gonorrhea. https://www.cdc.gov/gonorrhea/about/index.html
10. Centers for Disease Control and Prevention (CDC). Antibiotic Resistance Threats in the United States: Drug-Resistant Gonorrhea. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/gonorrhea-508.pdf
11. Ohnishi M, Golparian D, Shimuta K, et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? Detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrobial Agents and Chemotherapy. 2011;55(7):3538-3545.
12. Massachusetts Department of Public Health. Department of Public Health Announces First Cases of Concerning Gonorrhea Strain. https://www.mass.gov/news/department-of-public-health-announces-first-cases-of-concerning-gonorrhea-strain
13. WWLP. What Is “Super Gonorrhea”? Researchers Identify New Case in Male Patient. https://www.wwlp.com/
14. U.S. Food and Drug Administration (FDA). FDA Approves Two Oral Therapies to Treat Gonorrhea. https://www.fda.gov/news-events/press-announcements/fda-approves-two-oral-therapies-treat-gonorrhea
15. Centers for Disease Control and Prevention (CDC). Sexually Transmitted Disease Surveillance Network (SSuN): Success Story. https://www.cdc.gov/std/dstdp/sti-funding-at-work/success-stories/SSuN-Success-Story_FINAL.pdf
16. World Health Organization (WHO). Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP): Surveillance Report. https://iris.who.int/server/api/core/bitstreams/ed59e063-8034-4886-8fd5-41785ee836d6/content
17. Wi T, Lahra MM, Ndowa F, et al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action. PLOS Medicine. 2017;14(7):e1002344. https://doi.org/10.1371/journal.pmed.1002344