Antibiotic-Resistant Gonorrhea Emerges as a Growing Men’s Health Crisis During STI Awareness Month

TAXIS Pharmaceuticals Chief Scientific Officer Ajit Parhi, PhD, offers some insights on the disease burden, and an overview of his company’s pipeline around developing a therapy for this STI.

April is sexually transmitted infection (STI) Awareness Month, and with it brings renewed attention to these infections. One issue that is rapidly escalating beyond routine public health messaging: antibiotic-resistant gonorrhea. Once considered a straightforward infection to diagnose and cure, gonorrhea is evolving into a far more serious challenge—particularly for men. Experts now caution that this shift demands a reframing of the conversation, recognizing resistant gonorrhea not just as a general public health concern, but as a growing men’s health crisis with unique risks and consequences.

At the center of this concern is the speed at which gonorrhea has adapted to evade treatment. Over decades, the bacterium has developed resistance to nearly every major class of antibiotics, leaving clinicians increasingly reliant on a single remaining first-line therapy. This narrowing window of effective treatment is compounded by biological factors including rapid replication, genetic adaptability, and sophisticated defense mechanisms, that allow the pathogen to outpace drug development. The result is a widening gap between emerging resistance and available therapies, raising concerns about how long current treatments will remain effective.

The burden of this crisis is not evenly distributed. Men, especially gay and bisexual men, are disproportionately affected by both infection rates and the spread of drug-resistant strains. At the same time, men are less likely to engage in routine screening, often leading to delayed diagnoses and untreated infections that can worsen outcomes and fuel transmission. As awareness efforts intensify this April, experts emphasize the need for targeted education, improved screening practices, and investment in next-generation treatments to prevent gonorrhea from becoming an untreatable infection.

AXIS Pharmaceuticals Chief Scientific Officer Ajit Parhi, PhD, spoke to Contagion about this STI’s disease burden, and TAXIS Pharmaceuticals’ investigational therapy for it.

Contagion: During STI Awareness Month, why should antibiotic-resistant infections—particularly gonorrhea—be considered a growing men’s health crisis rather than just a broader public health issue?

Parhi: Gonorrhea is one of the most common sexually transmitted infections, and it is becoming increasingly difficult to treat because it has developed resistance to nearly every antibiotic used in clinical settings over the past several decades. While this is a broad public health issue, it is particularly a men’s health crisis.

Men, especially gay and bisexual men, represent a large share of gonorrhea cases, and the most drug-resistant strains have spread most rapidly through this population. At the same time, men are generally less likely to seek care or undergo routine STI screening than women, who typically have more regular healthcare interactions. This often leads to delayed diagnosis and attempts at self-treatment, which can worsen resistance.

If left untreated, gonorrhea can have serious consequences beyond the reproductive system. It can spread to the urinary tract, increase the risk of HIV transmission, and, in severe cases, affect the joints and heart. Despite these risks, gonorrhea is still often perceived as a routine STI rather than a condition with potentially systemic impacts, and it does not receive the level of public attention it warrants.

Contagion: Gonorrhea was once straightforward to treat. What has changed, and how quickly is resistance outpacing current treatment strategies?

Parhi: Historically, gonorrhea was very easy to treat. In the 1940s and 1950s, a single injection of penicillin could resolve the infection within days. However, the bacterium has proven to be highly adaptable and capable of evolving under pressure.

Gonorrhea can acquire genetic material from its environment and from other bacteria, allowing it to develop resistance mechanisms. It also multiplies very rapidly, every 20 to 30 minutes, which increases the likelihood of mutations. In addition, it has developed biological defenses such as efflux pumps that expel antibiotics from the bacterial cell and structural changes that prevent drugs from entering.

As a result, gonorrhea has developed resistance to nearly all major antibiotic classes, including sulfonamides, penicillin, tetracyclines, fluoroquinolones, and even cephalosporins. Today, ceftriaxone is the primary remaining first-line treatment, administered by injection. However, even this drug is beginning to show signs of strain, with documented treatment failures in some countries.

A key challenge is timing: resistance can emerge within five to 10 years of a drug’s introduction, but developing a new antibiotic typically takes around 10 years. This creates a persistent gap, leaving patients increasingly vulnerable.

Contagion: With the US now relying on a single remaining first-line therapy, how concerned should clinicians and patients be about treatment failure?

Parhi: There is some good news. In the United States, we have not yet seen confirmed cases of complete ceftriaxone treatment failure. However, treatment failures have already been documented in other parts of the world, particularly in Europe, and global resistance to ceftriaxone has increased significantly in recent years.

Given global travel and transmission patterns, it is likely only a matter of time before similar failures appear in the U.S. The country is effectively downstream from global resistance trends, and a single imported case could shift the situation.

There are also specific clinical challenges. Ceftriaxone is effective for genital infections but less reliable for throat infections, which are often asymptomatic and can go undetected. If clinicians test only genital sites, they may miss infections in the throat, leading to incomplete treatment and ongoing transmission.

While dosing has been increased to compensate, there are limits to how far this approach can go. Two newer drugs have been approved, but they share similar limitations; they are less effective for throat infections and do not introduce fundamentally new mechanisms of action. As a result, resistance could develop to these treatments within a relatively short timeframe.

Contagion: How do co-infections such as gonorrhea and chlamydia complicate diagnosis and treatment in men today?

Parhi: Co-infection is very common. When a man tests positive for gonorrhea, there is a strong likelihood that chlamydia is also present. These infections often produce similar symptoms, such as discharge and pain during urination, or no symptoms at all, making diagnosis more difficult.

The challenge is that they require different treatments. Previously, a combination approach—ceftriaxone for gonorrhea and a single dose of azithromycin—could effectively treat both infections. However, azithromycin is no longer reliable due to resistance.

Today, treatment often involves ceftriaxone plus a seven-day course of doxycycline for chlamydia. This introduces adherence challenges, as patients are less likely to complete a multi-day regimen compared to a single-dose treatment, and incomplete treatment increases the risk of persistent infection and further resistance.

Additionally, the newly approved drugs for gonorrhea do not address chlamydia, meaning patients with co-infections still require multiple therapies. This adds complexity and highlights the need for more comprehensive treatment options.

Contagion: Looking ahead, what gaps exist in the current antibiotic pipeline, and how could next-generation therapies change the trajectory of resistant STIs?

Parhi: The recent approval of two new drugs: zoliflodacin and gepotidacin, is encouraging, but significant gaps remain. Neither drug works reliably against throat infections, which are among the hardest to treat and can serve as reservoirs for resistance. Additionally, neither drug treats chlamydia, so co-infected patients still require combination therapy.

At present, no single approved therapy can effectively treat both gonorrhea and chlamydia together. This is a major limitation, especially given how frequently these infections occur together.

One of the enzymes that TAXIS Pharmaceuticals is targeting with its investigational therapies is called dihydrofolate reductase (DHFR), which is essential for bacterial survival. No currently approved therapies that treat both gonorrhea and chlamydia together target this enzyme.. Because TAXIS’ investigational therapy represents a novel mechanism, there are no existing resistance pathways that would make bacteria immediately immune.

Our investigational compounds have shown activity in preclinical studies against both gonorrhea and chlamydia, including drug-resistant strains. We have also seen promising results in animal models where our investigational therapy outperformed ceftriaxone, the current standard of care. Based on our preclinical studies, our investigational approach also appears to preserve the vaginal microbiome, which many existing antibiotics disrupt.

Given how thin the current pipeline of treatments for STIs is, there is an urgent need for continued investment and support for novel approaches that can address these gaps—particularly therapies capable of treating co-infections with new mechanisms of action.