The most highly drug-resistant cases of gonorrhea detected in the US to date appeared in two unrelated people in Massachusetts, state health officials announced Thursday.

The cases mark the first time that US isolates of the gonorrhea-causing bacterium, Neisseria gonorrhoeae, have shown complete resistance or reduced susceptibility to all drugs that are recommended for treatment.

Fortunately, both cases were successfully cured with potent injections of the antibiotic ceftriaxone, despite the bacterial isolates demonstrating reduced susceptibility to the drug. Ceftriaxone is currently the frontline recommended treatment for the sexually transmitted infection.

But health officials said the cases are a warning. "N. gonorrhoeae is becoming less responsive to a limited arsenal of antibiotics," they said.

Brewing resistance

For years, global surveillance data collected by the World Health Organization has shown that gonorrhea is becoming more and more resistant to our entire lineup of drugs, including frontline drugs like ceftriaxone. Though surveillance is spotty globally, a study of WHO's 2017–2018 data published in 2021 found N. gonorrhoeae isolates with decreased susceptibility or resistance to ceftriaxone have turned up in 21 of the 68 reporting countries, or 31 percent.

Resistance against alternative antibiotics was even higher. Among the 61 countries reporting data on an alternative antibiotic, azithromycin, 51 countries (84 percent) reported resistance. And of 51 countries reporting data on the alternative antibiotic treatment, cefixime, 24 countries (47 percent) reported resistance. For ciprofloxacin, an antibiotic largely abandoned as a gonorrhea treatment due to resistance, all 70 reporting countries found resistance.

"In many countries, ciprofloxacin resistance is extremely high, azithromycin resistance is rapidly increasing, and resistance or decreased susceptibility to ceftriaxone and cefixime continue to emerge," the WHO said in 2021. "Without new gonorrhoea treatments, there will be people with gonorrhoea infections that will be difficult to treat and cure."

The agency wasn't exaggerating. Last year, WHO added that reports of gonorrhea treatment failure are stacking up. "In the past decade, confirmed failure to cure gonorrhoea with ceftriaxone alone or combined with azithromycin or doxycyline was reported in Australia, France, Japan, Slovenia, Sweden, and the United Kingdom of Great Britain and Northern Ireland," WHO reported.

One of the isolates reported in Massachusetts yesterday demonstrated reduced susceptibility to ceftriaxone, cefixime, and azithromycin and resistance to ciprofloxacin, penicillin, and tetracycline in lab tests. The second isolate appeared to have a similar profile based on genetic data, Massachusetts' public health department reported. This strain of N. gonorrhoeae has been seen circulating in Asia-Pacific countries and has been detected in recent cases in the UK.

High cases

Alongside the worrying trend of increased resistance is the fact that gonorrhea cases are high worldwide and are on the rise in the US. In 2020, WHO estimated that there were 82.4 million new cases of gonorrhea worldwide. In the US, there were nearly 700,000 cases in 2021, up more than 25 percent from 2017, according to preliminary estimates from the Centers for Disease Control and Prevention.

In many people, gonorrhea has no symptoms. In others, it's so mild that it may be mistaken as a minor bladder infection or yeast infection. Over time, however, it can lead to pelvic inflammatory disease, severe pain, and fertility problems. Health officials stress the need for screening and surveillance to treat infections early before they become severe and have a chance to spread.

For the two Massachusetts cases, health officials are now working on contact tracing. Without a clear link between the two cases, officials say it's likely it's more widespread than currently known.

"The discovery of this strain of gonorrhea is a serious public health concern which DPH, the CDC, and other health departments have been vigilant about detecting in the US," Massachusetts Public Health Commissioner Margret Cooke said in a statement. "We urge all sexually active people to be regularly tested for sexually transmitted infections and to consider reducing the number of their sexual partners and increasing their use of condoms when having sex. Clinicians are advised to review the clinical alert and assist with our expanded surveillance efforts."