New Warning Signs that Gonorrhea Treatment May be Losing Effectiveness

More options urgently needed – encouraging progress toward one new treatment

For the first time in the United States, health officials have identified a cluster of gonorrhea infections that shows both decreased susceptibility to ceftriaxone and very high-level resistance to azithromycin. Ceftriaxone and azithromycin are the two drugs that make up the dual regimen that is the last available effective gonorrhea treatment option. An experimental oral antibiotic being tested in a clinical study may offer a new option for this sexually transmitted disease (STD). The findings were presented today at the 2016 STD Prevention Conference in Atlanta.

The new findings from the Hawaii investigation are even more concerning than data published by CDC earlier this year that showed evidence of emerging azithromycin resistance across the nation, but those cases were susceptible to ceftriaxone. This is the first cluster of cases to show decreased susceptibility to both of the currently recommended drugs in the United States.

“Our last line of defense against gonorrhea is weakening,” said Jonathan Mermin, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “If resistance continues to increase and spread, current treatment will ultimately fail and 800,000 Americans a year will be at risk for untreatable gonorrhea.”

CDC recommends dual therapy with a single shot of ceftriaxone and an oral dose of azithromycin to treat gonorrhea. Over the years, gonorrhea has developed resistance to nearly every class of antibiotics used to treat it. CDC has been closely monitoring early warning signs of resistance to both of the drugs used in the current treatment regimen. Reduced drug susceptibility can be an indicator of emerging resistance.

No confirmed failures of the CDC-recommended dual treatment regimen have been reported in the United States.

Gonorrhea is one of the most common STDs in the United States, but many people do not realize they are infected. Left untreated, it can cause serious health problems including infertility, pelvic inflammatory disease and life-threatening ectopic pregnancy in women.

There is a renewed interest in the development of new treatment options for gonococcal infections. At today’s STD Prevention Conference, researchers from Louisiana State University presented data showing an experimental oral antibiotic under development was generally safe and effective at treating gonorrhea in a phase II clinical trial supported by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health. These results will need to be confirmed in a large-scale clinical trial.

Concerning cluster of cases identified in Hawaii

Laboratory tests on gonorrhea isolates collected from seven individuals in Honolulu in April and May of 2016 showed resistance to azithromycin at dramatically higher levels than typically seen in the United States, according to researchers from the Hawaii State Department of Health. Additionally, isolates from five of the individuals also showed reduced susceptibility to ceftriaxone.

Although all patients were treated successfully using the recommended dual regimen, and no further cases have been identified since May, this cluster represents the first cases of decreased ceftriaxone susceptibility and very high-level azithromycin resistance occurring in the same isolate in the United States. Both the resistance pattern and the occurrence of a cluster of cases, which indicates the strain was able to spread, are cause for concern.

“Hawaii is on the front line for antibiotic-resistant gonorrhea – we’ve been one of the first states to see declining effectiveness of each drug over the years,” said Alan Katz, M.D., M.P.H., professor of public health at the University of Hawaii, member of the Hawaii State Board of Health, and staff physician and medical consultant at the Hawaii State Department of Health’s Diamond Head STD Clinic. “That’s made us extremely vigilant, so we were able to catch this cluster early and treat everyone found who was linked to the cluster. But the future risk of gonorrhea becoming resistant to both of the recommended therapy medications in the United States is troubling.”

“Using both drugs ensures patients are cured of infection and prevents further transmission, but to preserve this option, providers should treat infections right away with the combination of azithromycin and ceftriaxone,” said Gail Bolan, M.D., director of CDC’s Division of STD Prevention. “All health care providers should also promptly report any suspected treatment failure to local health officials and CDC to ensure rapid response to cases or clusters of concern.”

New gonorrhea treatment shows promise in early clinical trials

Historically, when gonorrhea developed resistance to antibiotics, CDC revised its treatment guidelines to recommend other available and effective medications. However, there are now no highly reliable, widely available, affordable, and well-tolerated backup options available, making research into new drugs particularly urgent.

ETX0914 works differently from any currently marketed antibiotic. As a single-dose oral therapy, it could be used as an alternative to ceftriaxone injection as a component of recommended therapy for gonorrhea, replacing the need for intramuscular injection. CDC researchers contributed to the preclinical evaluation of the antibiotic by showing it was active in the laboratory against strains of gonorrhea that were resistant to other existing classes of drugs.

In the randomized controlled trial reported today, researchers treated 179 participants (167 men and 12 women) for gonorrhea using ETX0914 alone (at either 2g or 3g dosage levels) or ceftriaxone alone. All patients in the 3g ETX0914 arm (47/47) and 98 percent of patients in the 2g arm (48/49) were cured. A small number of patients (21/179) reported side effects, but most were mild and primarily gastrointestinal.

“Our research team and study participants take the possibility of untreatable gonorrhea very seriously,” said Stephanie N. Taylor, M.D., professor of medicine and microbiology at Louisiana State University Health Sciences Center and the trial’s lead investigator. “We are very pleased with these results and look forward to seeing ETX0914 advance through additional clinical studies.”

Enhanced monitoring, rapid response essential to fend off untreatable gonorrhea

Additional drug candidates as well as ongoing efforts to preserve the effectiveness of the current regimen are still needed. This includes maintaining investments in routine gonorrhea testing and treatment services, enhancing systems that monitor for emerging drug resistance, and building rapid detection and response capacity to respond to potential outbreaks of isolates with reduced cephalosporin susceptibility.

“In Hawaii, the system worked,” said Dr. Mermin. “Front-line providers diagnosed and treated infections, public health officials quickly detected resistance, and we were able to use cutting-edge lab technologies to track its spread and treat people who were linked to the cluster. A strong STD prevention and control infrastructure is critical to ensure we’re ready to confront drug resistance not just in Hawaii, but nationwide.”

The combination therapy of azithromycin and ceftriaxone recommended by CDC still works. CDC encourages providers to adhere to the recommended dual therapy as outlined in CDC’s most recent STD Treatment Guidelines.

As part of the federal government’s Combating Antibiotic Resistant Bacteria (CARB) Action Plan, CDC works closely with state and local health departments to monitor and test for drug-resistant gonorrhea and enhance their capacity to quickly find and treat affected individuals.

CDC provides funds to every state for STD prevention services. New in 2016, CDC used additional resources targeted for addressing antibiotic resistance to bolster existing state and local STD programs; to introduce new laboratory tools and services; and build rapid response capacity for outbreak response.

 

For additional information, visit www.cdc.gov/nchhstp/newsroom.

###

CDC works 24/7 protecting America’s health, safety and security. Whether diseases start at home or abroad, are curable or preventable, chronic or acute, stem from human error or deliberate attack, CDC is committed to respond to America’s most pressing health challenges.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES