Gonorrhea may soon become untreatable.

The Centers for Disease Control and Prevention reported Thursday that the wily Neisseria gonorrhoeae bacteria may be developing resistance to the only two antibiotics left that can cure the sexually transmitted disease.

The drugs, azithromycin and ceftriaxone, are used in combination to treat gonorrhea, a strategy experts hope will prolong the period during which these critical drugs will work.

But a nationwide surveillance program showed rises in the percentage of gonorrhea samples that were resistant to one or the other drug in 2014. In the case of azithromycin, there was a four-fold rise in the portion of samples that were resistant.

The rates are still modest: the percentage of samples resistant to azithromycin rose from 0.6 percent to 2.5 percent, and for ceftriaxone it doubled, from 0.4 percent to 0.8 percent. But these are red flags for scientists tracking gonorrhea's march through the antibiotic armamentarium.

"It is low. But what we do know is that this bacteria has demonstrated the ability, repeatedly, to develop antibiotic resistance to the drugs that have been used for it," the first author of the report, Dr. Robert Kirkcaldy, told STAT.

"The potential for untreatable gonorrhea is a very real possibility in the future."

Gonorrhea is common. In 2014, more than 350,000 people in the US were diagnosed with it. People who are infected may have no symptoms, or may notice pain, burning or discharge, in the site of infection — usually the uterus, anus, throat, mouth or penis.

Left untreated, it can cause infertility or chronic pelvic pain in women, and in men, testicular pain and infertility in rare cases. The bacteria can also get into the blood, infecting joints, and on rare occasions can move into the heart — which can be fatal.

An infected pregnant woman can infect her infant during childbirth; the baby can develop an eye infection that can be vision-threatening.

Since the dawn of the antibiotic era, these bacteria have been steadily mowing down every antibiotic placed in their path, Kirkcaldy said.

Where resistance was seen to azithromycin or ceftriaxone, the infecting strain was still susceptible to the other drug and the cases were cured, he said. But the specter of pan-resistant gonorrhea looms large.

"We think ... it's a matter of when and not if with resistance," he said. "This bug is so smart and can mutate so rapidly."

Dr. Vanessa Allen agrees. The chief medical microbiologist for Public Health Ontario, Allen has been tracking the development of resistance in gonorrhea for some time. The rates Ontario is seeing for these drugs is similar to what the CDC is reporting, she told STAT.

"It doesn't seem to be a blip in the Ontario context," said Allen, who has more recent data than the CDC report analyzes. "It (resistance) seems to persist."

Kirkcaldy said one of the things that makes gonorrhea so difficult is that once it acquires resistance to a drug, it doesn't appear to lose it. The bacteria are still invulnerable to antibiotics that haven't been used to treat it for decades.

Kirkcaldy declined to speculate on how quickly the bacteria may acquire the ability to evade these azithromycin and ceftriaxone, saying it's too hard to predict.

Using the combination therapy should buy more time. Allen said the report is heartening as it suggests US doctors have rapidly adopted the combination therapy, as recommended by CDC.

Some companies are working on new antibiotics, "but these could be years away," Kirkcaldy said. In the meantime, it's critical to get people to start taking the threat seriously, he said, so that they take steps to prevent themselves from being infected with gonorrhea.

"The trend is known," said Allen. "At some point, it's just: How much can we slow it down?" "It will happen and we don't have any other options."

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