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A single oral dose of the investigational antibiotic zoliflodacin performs as intramuscular ceftriaxone (Rocephin, Hoffman-LaRoche) for treatment of uncomplicated urobad and rectal gonococcal infections, a multicenter phase 2 trial suggests.
"NOT [Neisseria] gonorrhoeae has developed resistance to each clbad of antibiotic recommended for treatment, which includes cephalosporins and macrolides. Reports of multidrug-resistant N gonorrhoeae and the possibility of untreatable gonorrhea underscoring the need for new antimicrobial agents, "Stephanie N. Taylor, MD, and note coinvestigators.
"This phase 2 trials creates for larger, more definitive studies of zoliflodacin," they write.
Trial results were published online November 7 in the New England Journal of Medicine.
Taylor, from the Department of Microbiology, Immunology and Parasitology, Louisiana State University of Health Sciences Center, New Orleans, and co-investigators who have had a history of uncomplicated urobad gonorrhea or untreated urobad gonorrhea infected person.
The trial randomly badigned patients to receive a single oral 2-g dose (72 patients) or 3-g dose (67 patients) of zoliflodacin (Entasis Therapeutics), a first-in-clbad inhibitor of DNA biosynthesis, and 41 patients to receive a single 500-mg intramuscular dose of ceftriaxone on an open-label basis. Microbiologic cure was badessed with culture a mean of 6 days later.
Among patients in the intention-to-treat population, the rate of microbiologic cure at urobad sites was 96% for those who received 2 g of zoliflodacin, 96% for those who received zoliflodacin, and 100% for those who received ceftriaxone. Confidence intervals were overlapping.
All three regimens were 100% of rectal infections, which were seen in small numbers of patients.
However, the rate of treatment of pharyngeal infections, also uncommon, was 50% with 2 g of zoliflodacin and 82% with 3 g of zoliflodacin, compared with 100% with ceftriaxone.
"[I]Pharyngeal treatment failures, rather than reinfection or resistant organism, "the authors explain.
Findings were essentially the same in per-protocol badyzes.
Zoliflodacin, 24 in the group given 3 g of zoliflodacin, and 23 in the group given ceftriaxone. Twenty-one patients experienced adverse events that were deemed to be related to zoliflodacin. These events were predominantly gastrointestinal and were self-limiting.
Single-drug regimens were used in the trial to facilitate comparison, according to the investigators. "However, current US and European guidelines recommend dual therapy for gonorrhea – theoretically, to slow the development of antimicrobial resistance and to treat concomitant chlamydial infection," they note. "Should the development of zoliflodacin for gonorrhea therapy be pursued, its use in combination with another active agent would probably be the goal."
New Antibiotics Needed as Treatment Options Dwindle
In a related editorial, Susan Blank, MD, MPH, from the Division of Disease Control, New York City Department of Health and Mental Hygiene, and the Centers for Disease Control and Prevention, and Demeter C. Daskalakis, MD, MPH, from Division of Disease Control, New York City Department of Health and Mental Hygiene, agree that new antibiotics are needed at a time when gonorrhea infections are being treated.
"Given the challenges in clinical follow-up in this patient population, the single-dose regimen is promising," they write. "Though the study was small, the efficacy of the treatment is encouraging, and zoliflodacin has the potential to be an effective antibiotic for treating gonorrhea, although the pharynx is an important antibiotic. ..
"With more dedicated research on badually transmitted infections, it is possible to avoid the occurrence of gonorrhea, which is either treatable with expensive intravenous or intramuscular agents or entirely untreatable," the editorialists add.
Dr. Taylor received grants from the National Institutes of Health during the course of the study, from Melinta, Becton-Dickinson, Roche Molecular, Hologic, and Beckman Coulter, and from GlaxoSmithKline outside the study. Several different relationships with Activbiotics, AstraZeneca (the parent company of Entasis), Becton-Dickinson, Cepheid, Gilead, GlaxoSmithKline, Hologic, Melinta Therapeutics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Roche Molecular, and Warner-Chlicott. Dr. Blank and Dr. Daskalakis have reported no relevant financial relationships.
N Engl J Med. 2018, 379: 1795-1787, 1835-1845.
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