Gonorrhea is nearly impossible to treat, but a new drug offers hope

Dec. 2, 2018 / 6:23 PM GMT

By Shamard Charles, M.D.

It may soon be impossible to treat gonorrhea, according to the World Health Organization, as two-thirds of the world’s countries have reported gonorrhea cases that resist all known antibiotics.

If that happens, doctors warn, more people will be left with an incurable infection that, while not life-threatening, can cause significant health problems. What’s more, it could mark the beginning of the post-antibiotic era of medicine.

But a new drug that specifically targets antibiotic-resistant gonorrhea is giving researchers hope. Recent trials have shown that this drug is 96 percent effective at killing gonorrhea.

The infection is widespread and intractable. In 2017, the Centers for Disease Control and Prevention reported that gonorrhea was the second most common sexually transmitted disease in the U.S., with 555,608 reported cases. An estimated 78 million people are infected with the bacteria worldwide, according to the WHO, and this number may be much higher because underreporting remains a problem.

Rates of reported cases of gonorrhea by age group and sex in the United States in 2017CDC

A dependable treatment is urgently needed.

“Since there is no vaccine to prevent gonorrhea, and the possibility of untreatable gonorrhea is looming larger, it is imperative that we develop new drugs to treat it,” said Dr. Stephanie Taylor, professor of medicine and microbiology at LSU Health New Orleans School of Medicine.

With the world using the last viable batch of antibiotics to treat gonorrhea, the Global Antibiotic Research and Development Partnership, a drug resistance initiative, has partnered with Entasis Therapeutics, a U.S. biotech company, to speed up the development of the new drug, zoliflodacin.

In November, the last phase of the single-dose antibiotic trials took place, involving 650 people in Thailand, South Africa, the U.S. and Europe. Researchers hope that the drug will be available to the public by 2023 — the first new drug to treat drug-resistant gonorrhea in over two decades.

So why has it taken so long for scientists to come up with a new treatment?

“The bacterium has steadily evolved to be less susceptible to the antibiotics used for treatment,” said Dr. Edward W. Hook III, an expert on sexually transmitted diseases and a professor of infectious diseases at the University of Alabama at Birmingham medical school. “The ongoing progression of antibiotic resistance has now been combined with a lack of alternatives.”

What makes gonorrhea so hard to treat is its ability to acquire resistance genes and mutations that enable it to survive and adapt to each new threat. Gonorrhea has another nasty advantage over other infectious diseases: the genes of other types of bacteria can lose resistance once they’re not exposed to antibiotics; gonorrhea holds onto its resistance genes.

The complicated history of gonorrhea

In 1946, the first cases of gonorrhea strains resistant to large doses of penicillin were recorded. Thirty years later, researchers studied rare cases of gonorrhea resistance in California and London that led to the discovery of two methods that the bacteria developed to avoid being killed by penicillin: some produced a protein, beta-lactamase, that inactivates penicillin, and others contained damaged DNA that allowed the mutated bacteria to survive in the presence of penicillin.

Researchers found new and seemingly easier treatment regimens — one single pill that could kill the bacteria — but ever-changing regimens were a sign that they had begun to fail. Earlier penicillin-based multidrug treatments were replaced by 1966 with tetracycline, which easily killed 94 percent of gonococcal strains.

The bacteria eventually found ways to survive tetracycline, and resistance quickly developed. Over the next four decades new drugs would be introduced and work initially, only to fail just as tetracycline had.

“We have known for a long time, 20 to 25 years, that the gonorrhea bacteria may be resistant to several antibiotics including penicillin, but the rate of resistance to traditional treatment has hastened in recent years,” said Dr. Frank Palella, a professor of infectious diseases at Northwestern Memorial Hospital.

Currently, the CDC recommends a combination drug therapy of two different antibiotics in the form of an intramuscular shot and a pill — plus azithromycin or doxycycline.

Why do antibiotics stop working?

Not all of the current drugs have stopped working — yet. But the options are fewer and fewer, said Hook.

Doctors prescribing drugs that no longer work against gonorrhea are part of the problem. Astudy published in the BMJ in 2018 found that one in five general practitioners in England were still prescribing ciprofloxacin, an ineffective antibiotic, even though treatment guidelines had changed 12 years earlier.

Also, the infection is often asymptomatic, so people don’t seek treatment and unknowingly spread the disease. As transmission rates rise, so does the possibility of new mutations of the bacteria.

Gonorrhea rarely kills, so why is it so important to treat it?

If left untreated in women, the infection can cause long-term abdominal pain and pelvic inflammatory disease, which can lead to ectopic pregnancy and infertility. Pregnant women can also pass the disease along to their newborns. In men, untreated gonorrhea can cause epididymitis — an inflammation of the small, coiled tube in the rear portion of the testicles where the sperm ducts are located. The condition is treatable, but if not treated, it can lead to infertility.

In rare cases, gonorrhea can spread to other organs.

Common gonorrhea symptoms include:

• a burning sensation
• discomfort during urination
• a thick yellow-green discharge from the penis or vagina.

What can be done?

According to the CDC, a coordinated effort among providers, state and local health departments, and patients is needed for rapid detection and treatment of sexually transmitted diseases, especially in areas hardest hit by the STD epidemic.

“The communities in which there is the greatest occurrence of infection are those that traditionally have less access to care, so we have to target our interventions to those communities where the need is greatest,” Palella told NBC News.

Currently, 50 percent of STD cases occur in youth ages 15 to 24, and that number may be higher in low socioeconomic groups and among gay and bisexual populations, along with men who have sex with men. Women aged 20 to 24 are at the highest risk of contracting STDs, including gonorrhea.

Palella encourages teenagers and adults to practice safe sex and get routine STD screening to help limit the development of gonorrhea superbugs.

“If you’re sexually active, undergo routine STD screening whether you are having symptoms or not,” said Palella. “This is the surefire way to get infections treated and to prevent the spread of it.”

Shamard Charles, M.D.

Dr. Shamard Charles is a physician-journalist for NBC News and Today, reporting on health policy, public health initiatives, diversity in medicine, and new developments in health care research and medical treatments.