From the Journals

Single-dose zoliflodacin successfully treats uncomplicated urogenital gonorrhea

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In a time of danger, a step forward

This study represents a “step forward” in identifying new antimicrobial treatment options for patients with gonorrhea, according to Susan Blank, MD, and Demetre C. Daskalakis, MD.

“Given the challenges in clinical follow-up in this patient population, the single-dose regimen is promising,” Dr. Blank and Dr. Daskalakis wrote in a editorial.

While zoliflodacin has the potential to be an effective treatment for gonorrhea, its activity needs to be better defined, particularly in key anatomical sites of infection such as the pharynx, where limited activity was observed.

Progression of resistance of Neisseria gonorrhoeae is an “ever-present concern” given the history of the organism, the authors wrote.

“We are facing the real danger of multidrug-resistant, nearly untreatable gonorrhea,” they wrote. “To avoid untreatable cases of this high-incidence infection, we need to advance diagnostic technology and develop treatments with different mechanisms of action.”

Dr. Blank and Dr. Daskalakis are with the division of disease control in the New York City Department of Health and Mental Hygiene. Their editorial appears in the New England Journal of Medicine . Both reported having no conflicts of interest.



A new antibiotic successfully treated uncomplicated urogenital and rectal gonococcal infections, but was not as effective as ceftriaxone in treating pharyngeal infections, according to the results of a randomized, phase 2 study.

This image shows a positive fluorescent antibody test for the Gram-negative bacterium Neisseria gonorrhoeae. Centers for Disease Control and Prevention

This image shows a positive fluorescent antibody test for the Gram-negative bacterium Neisseria gonorrhoeae.

About 96% of patients with infection at urogenital sites had microbiologic cure with zoliflodacin, a novel antimicrobial agent that inhibits DNA biosynthesis. The cure rate was 100% for rectal infections, but was just 50%-82% for pharyngeal infections, though few participants in this study had infection at either of those sites.

The study investigators, led by Stephanie N. Taylor, MD, professor of medicine and microbiology at Louisiana State University, New Orleans, wrote that the need for new antimicrobial agents has been underscored by reports of multidrug-resistant Neisseria gonorrhoeae and the possibility of untreatable gonorrhea.

“This phase 2 trial creates equipoise for larger, more definitive studies of zoliflodacin,” Dr. Taylor and her coauthors wrote in the New England Journal of Medicine.

At this point, N. gonorrhoeae has developed resistance to every recommended antibiotic class, including cephalosporins and macrolides, they added.

Zoliflodacin (ETX0914) is an antimicrobial that has received fast-track designation from the Food and Drug Administration specifically for development as an oral treatment for gonococcal infections, the authors noted.

“The mechanism of action of zoliflodacin differs from currently available therapies in that it inhibits microbial biosynthesis by arresting the cleaved covalent gyrase complex and the formation of fused circular DNA required for biosynthesis,” they wrote.

Dr. Taylor and her colleagues studied single 2- and 3-gram doses of zoliflodacin in comparison with 500 mg of intramuscular ceftriaxone in 181 patients with uncomplicated urogenital gonorrhea enrolled in the open-label, randomized, phase 2 study between November 2014 and December 2015.

A total of 141 patients included in the microbiologic intention-to-treat analysis had confirmed positive urethral or cervical cultures. Cures were seen in 55 of 57 infections treated with 2 grams (96%) and 54 of 56 treated with 3 grams (96%) of zoliflodacin, and in 28 of 28 infections (100%) treated with ceftriaxone.

Of 15 confirmed rectal infections, 100% were cured, including 12 treated with zoliflodacin at 2 or 3 grams and 3 treated with ceftriaxone. Of 23 confirmed pharyngeal infections, cures were seen in 4 of 8 (50%) treated with 2 grams of zoliflodacin and 9 of 11 (82%) treated with 3 grams, compared with 4 of 4 cured (100%) with ceftriaxone.

That suggests zoliflodacin was not as effective as ceftriaxone in treating pharyngeal gonorrhea, which is generally considered more difficult to treat than infections at other sites, according to Dr. Taylor and her coauthors.

“Currently, this limitation has not curtailed recommendations for the use of drugs such as spectinomycin or fluoroquinolones for the treatment of gonorrhea,” they wrote.

The study was funded by the National Institutes of Health and Entasis Therapeutics. Dr. Taylor reported grants from the NIH during the study, and other disclosures related to a variety of pharma companies. Her coauthors reported disclosures related to AstraZeneca (parent company of Entasis, which is developing zoliflodacin) and other pharmaceutical companies.

SOURCE: Taylor SN et al. N Engl J Med. 2018 Nov 7; 379:1835-45.

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