New antibiotic shows promise against gonorrhea amid news of resistant Hawaii strain

Health officials in Hawaii say a strain of gonorrhea has shown reduced susceptibility to the last known effective cure. The good news is that researchers reported that a novel antibiotic has shown promise against gonorrhea in a phase 2 trial.

The drug, a single-dose oral therapy called ETX0914 (Entasis Therapeutics), was active against strains of gonorrhea that are resistant to existing classes of drugs, according to data presented at the 2016 STD Prevention Conference in Atlanta.

“It would be a brand-new class of antibiotics. There are none on the market right now with this mechanism of action,” Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University and lead investigator for the trial, said during a news conference.

Troubling signs in Hawaii

Gonorrhea is one of the most common STDs, with about 820,000 new infections estimated to occur in the United States annually, according to the CDC. It often goes undiagnosed and can cause serious health problems if left untreated.

The promising results for ETX0914 come as gonorrhea has developed resistance to almost every class of antibiotics used to treat it. A combination of ceftriaxone and azithromycin is the last available effective cure for the STD, the CDC reports.

In a discovery that should cause concern about the disease’s growing drug resistance, researchers from the Hawaii State Department of Health (DOH) said they identified the first cluster of gonorrhea in the United States that showed both decreased susceptibility to ceftriaxone and very high resistance to azithromycin.

Hawaii is aggressive in culturing gonorrhea and testing it for susceptibility to antibiotics, according to Alan Katz, MD, MPH, professor of public health at the University of Hawaii and member of the Hawaii State Board of Health. The result is a rapid detection system that outpaces other states, he said during the news conference.

Jonathan Mermin, MD, MPH

Jonathan Mermin

“We’re on top of things,” Katz said. “People come to Hawaii to vacation. The CDC comes to Hawaii to work. They come to go to our labs and look for our isolates.”

According to the DOH, isolates from seven patients in Hawaii showed resistance to azithromycin at dramatically higher levels than are typically seen in the U.S. Isolates from five of the patients also showed reduced susceptibility to ceftriaxone, the researchers found. Katz said the cases were from April and May.

“It would seem that in the battle between humans and pathogens, gonorrhea is a formidable opponent,” Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said during the news conference.

Promising results

The CDC recommends treating gonorrhea with a 250-mg intramuscular injection of ceftriaxone and 1 g of oral azithromycin. Even with evidence of increased resistance, the CDC does not think there is enough evidence to warrant changing its recommendations or to increase the currently recommended doses, according to Gail Bolan, MD, director of the CDC’s Division of STD Prevention.

“We just really want people to be aware that we are concerned that this is not going in the right direction,” Bolan said during the news conference.

Gail Bolan, MD

Gail Bolan

ETX0914 could be used as an alternative to ceftriaxone, eliminating the need for an injection. Some 179 participants aged 18 to 53 years were enrolled in the randomized controlled phase 2 trial between November 2014 to December 2015, including 167 men and 12 women. Each participant received either 2 g or 3 g ETX0914 or a 500-mg dose of ceftriaxone.

In the per-protocol population, every patient who received either a 3 g-dose of ETX0914 (n = 47) or a dose of ceftriaxone (n = 21), and 98% (n = 48) of those receiving 2 g of ETX0914 were cured of gonorrhea. Further, just 12% of the total participants in the trial reported side effects, mostly gastrointestinal, and all were related to ETX0914, Taylor said.

No new class of antibiotics has come on the market since 1984, but Mermin tempered the promising results for ETX0914 with a warning about the seriousness of drug-resistant gonorrhea.

“Even if the new treatment we heard about today is successful,” he said, “it’s clear that we will need to develop even more options quickly.”

Disclosures: Bolan, Katz and Mermin report no relevant financial disclosures. Taylor is the lead investigator for the ETX0914 clinical trials.

Health officials in Hawaii say a strain of gonorrhea has shown reduced susceptibility to the last known effective cure. The good news is that researchers reported that a novel antibiotic has shown promise against gonorrhea in a phase 2 trial.

The drug, a single-dose oral therapy called ETX0914 (Entasis Therapeutics), was active against strains of gonorrhea that are resistant to existing classes of drugs, according to data presented at the 2016 STD Prevention Conference in Atlanta.

“It would be a brand-new class of antibiotics. There are none on the market right now with this mechanism of action,” Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University and lead investigator for the trial, said during a news conference.

Troubling signs in Hawaii

Gonorrhea is one of the most common STDs, with about 820,000 new infections estimated to occur in the United States annually, according to the CDC. It often goes undiagnosed and can cause serious health problems if left untreated.

The promising results for ETX0914 come as gonorrhea has developed resistance to almost every class of antibiotics used to treat it. A combination of ceftriaxone and azithromycin is the last available effective cure for the STD, the CDC reports.

In a discovery that should cause concern about the disease’s growing drug resistance, researchers from the Hawaii State Department of Health (DOH) said they identified the first cluster of gonorrhea in the United States that showed both decreased susceptibility to ceftriaxone and very high resistance to azithromycin.

Hawaii is aggressive in culturing gonorrhea and testing it for susceptibility to antibiotics, according to Alan Katz, MD, MPH, professor of public health at the University of Hawaii and member of the Hawaii State Board of Health. The result is a rapid detection system that outpaces other states, he said during the news conference.

Jonathan Mermin, MD, MPH

Jonathan Mermin

“We’re on top of things,” Katz said. “People come to Hawaii to vacation. The CDC comes to Hawaii to work. They come to go to our labs and look for our isolates.”

According to the DOH, isolates from seven patients in Hawaii showed resistance to azithromycin at dramatically higher levels than are typically seen in the U.S. Isolates from five of the patients also showed reduced susceptibility to ceftriaxone, the researchers found. Katz said the cases were from April and May.

“It would seem that in the battle between humans and pathogens, gonorrhea is a formidable opponent,” Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said during the news conference.

Promising results

The CDC recommends treating gonorrhea with a 250-mg intramuscular injection of ceftriaxone and 1 g of oral azithromycin. Even with evidence of increased resistance, the CDC does not think there is enough evidence to warrant changing its recommendations or to increase the currently recommended doses, according to Gail Bolan, MD, director of the CDC’s Division of STD Prevention.

“We just really want people to be aware that we are concerned that this is not going in the right direction,” Bolan said during the news conference.

Gail Bolan, MD

Gail Bolan

ETX0914 could be used as an alternative to ceftriaxone, eliminating the need for an injection. Some 179 participants aged 18 to 53 years were enrolled in the randomized controlled phase 2 trial between November 2014 to December 2015, including 167 men and 12 women. Each participant received either 2 g or 3 g ETX0914 or a 500-mg dose of ceftriaxone.

In the per-protocol population, every patient who received either a 3 g-dose of ETX0914 (n = 47) or a dose of ceftriaxone (n = 21), and 98% (n = 48) of those receiving 2 g of ETX0914 were cured of gonorrhea. Further, just 12% of the total participants in the trial reported side effects, mostly gastrointestinal, and all were related to ETX0914, Taylor said.

No new class of antibiotics has come on the market since 1984, but Mermin tempered the promising results for ETX0914 with a warning about the seriousness of drug-resistant gonorrhea.

“Even if the new treatment we heard about today is successful,” he said, “it’s clear that we will need to develop even more options quickly.”

Disclosures: Bolan, Katz and Mermin report no relevant financial disclosures. Taylor is the lead investigator for the ETX0914 clinical trials.