How new diagnostics and surveillance could shape the fight against drug-resistant gonorrhea

Antimicrobial resistance is widely recognized as one of the most urgent and fast-moving threats in global public health. The World Health Organization has identified bacterial antimicrobial resistance (AMR) as a major global health challenge, with drug-resistant infections already contributing to more than 1 million deaths worldwide each year. While resistance affects many pathogens, gonorrhea has become one of the clearest examples of how quickly bacteria can adapt to repeated antibiotic exposure and outpace available treatments.

Neisseria gonorrhoeae, the bacterium that causes gonorrhea, remains one of the most common bacterial sexually transmitted infections globally, with an estimated 80 million new infections annually. Over the past several decades, it has developed resistance to nearly every major class of antibiotics used against it, including penicillin, tetracyclines, macrolides, and fluoroquinolones. In some regions, reduced susceptibility to ceftriaxone, the current backbone of recommended treatment, has also been reported, raising concern about the long-term durability of remaining therapies.

Below, Yonatan Grad, physician-scientist and infectious disease epidemiologist and Harvard T.H. Chan School of Public Health, professor of immunology and infectious diseases, and director of the Center for Communicable Disease Dynamics, discusses how drug-resistant gonorrhea reflects broader challenges in antimicrobial resistance. In the recent Research & Innovation talk, “Addressing the Global Challenges of Drug-Resistant Gonorrhea”, moderated by Louise Ivers, faculty director of the Harvard Global Health Institute, Grad examined how increasing resistance in Neisseria gonorrhoeae is reshaping approaches to treatment, prevention, and surveillance, and emphasized that the challenge is not only developing new tools, but ensuring they are deployed in ways that preserve long-term effectiveness.

HGHI: What are the major barriers to implementing diagnostics that can both identify gonorrhea and guide antibiotic selection in real-world clinical settings?

Grad: We may have to wait a bit to see diagnostics that can both identify a pathogen and report drug susceptibility quickly enough to be useful clinically.

There is data that allows us to predict susceptibility to ciprofloxacin from pathogen DNA sequence. For example, if the gyrA codon 91 position is serine, the pathogen is susceptible, and if it’s phenylalanine, it is resistant.

Technologies to test for this variant through PCR and related methods exist, but so far they’re too slow for point-of-care testing.

In much of the world, management of sexually transmitted infections is syndromic. We don’t have access to point-of-care diagnostics that we would like to have access to diagnostics that can give us rapid information both on what pathogen is causing the symptoms and ideally information on what drugs it might be susceptible to.

This is the kind of information we often get in treating people with urinary tract infections, for example, easy diagnostics and rapid information on drug susceptibility. But it is very hard to get. We don’t have the tools for it yet for STIs.

So in most of the world, treatment really is syndromic. As diagnostics are developed, and there is a huge interest in this field and a lot of investment, with many startups and established companies trying to make these tools, those diagnostics will eventually allow point-of-care diagnosis and treatment.

As those tools become available, they will help inform both better surveillance and better treatment of individual patients with tailored therapy, but I think that is still a ways off right now.

If such diagnostics do become available, I think cost will also be central. What will be the cost-effectiveness argument for paying for and using such diagnostics instead of maintaining current syndromic management?