New antibiotic effective in urogenital and rectal gonorrhea

Zoliflodacin, a new antibiotic, was effective in the treatment of urogenital gonorrhea, as well as in a small proportion of patients with double-sided gonorrhea infections, according to an open-label phase II trial.

Microbiological healing has been documented in 96% of patients with urogenital gonorrhea and all patients with rectal gonorrhea who received a single oral dose (2 or 3 g) of zoliflodacin, reported Stephanie N. Taylor, MD, of University of Louisiana Health Sciences Center in the State of New York. Orleans and his colleagues.

However, the microbiological cure rate in patients with pharyngeal infections following zoliflodacin treatment ranged from 50% to 82%, depending on the dose, according to the authors. New England Journal of Medicine.

The prevalence of gonorrhea has increased in the United States, by 67% since 2013, according to the latest estimates from the CDC. The authors also noted that the CDC had revised the infection treatment guidelines three times in response to treatment failures and increased minimum inhibitory concentrations for current antibiotics.

They lamented the absence of "any other highly reliable antimicrobial agent, administered orally and affordably, with minimal side effects".

In addition, an expert on HIV recently raised the need for new strategies to combat sexually transmitted infections (STIs), such as gonorrhea, including the development of new treatments.

Zoliflodacin (AZD0914 or ETX0914) has recently received the FDA's "fast track" designation. The drug is a spiropyrimidinetrone that inhibits the biosynthesis of DNA via a unique mechanism, according to Taylor and his colleagues.

The researchers recruited non-pregnant men and women into sexual health clinics around the United States. Participants were eligible if they were between 18 and 55 years old, had signs and symptoms of urogenital gonorrhea, untreated urogenital gonorrhea, or sexual contact in the last 14 days. who has had gonorrhea.

Patients were randomized in a 7: 7: 4 ratio to receive a single oral dose of zoliflodacin at 2 or 3 g or an intramuscular dose of 500 mg of ceftriaxone. The authors noted that it was "twice the dose recommended by the CDC", but that it was used to meet the regulatory requirements of the FDA and the European Medicines Agency and that 39 it "corresponded to the recommended European dose," they said.

The primary endpoint for assessing effectiveness was microbiological cure, defined as "the proportion of participants with urogenital infection and experiencing a conversion from a baseline positive value." N. gonorrhoeae culture to a negative culture during the focus visit ".

A total of 179 participants (167 men and 12 women) were randomized, including four with HIV. After excluding 38 participants from the efficacy analysis due to negative cultures, 28 received ceftriaxone, 57 received 2 g zoliflodacin and 56 received 3 g zoliflodacin.

Of this "micro-intention-to-treat" population, there were 141 with positive cervical or urethral cultures, 23 with positive pharyngeal cultures and 15 with positive rectal cultures.

In this population, 55 of 57 urogenital infections in the 2 mg zoliflodacin group, 54 of 56 in the 3 g group, and 28 of the 28 in the ceftriaxone group had documented microbiological healing. Pharyngeal gonorrhea was cured in four of the eight patients in the 2 g zoliflodacin group, nine in 11 in the 3 g group and four of the four in the ceftriaxone group. All rectal infections in all groups were cured, the authors said.

In terms of safety, 84 adverse events were reported, including 24 in the zoliflodacin 2 g group, 37 in the 3 g group, and 23 in the ceftriaxone group. There were 21 participants with adverse events assessed as being related to zoliflodacin, and most were gastrointestinal and "spontaneously resolving," said the authors.

The authors added that data was lacking at the low enrollment rate of women and participants with rectal infections.

Susan Blank, MD, and Demetre C. Daskalakis, MD, of New York City's Department of Health and Mental Health, have called this study a "step forward" in the need for new antimicrobial options for the treatment of gonorrhea.

"Given the difficulties of clinical follow-up in this patient population, the single-dose regimen is promising," they wrote. "Although the study is small in size, the demonstrated efficacy is encouraging and zoliflodacin could be an effective antibiotic for treating gonorrhea, although the limited activity seen in the sites of Key anatomical infection such as the pharynx needs to be better defined. "

Blank and Daskalakis also emphasized the need to develop better diagnostic tests, including point-of-care molecular diagnostics with "rapid diagnosis of gonorrhea with real-time evaluation of antimicrobial susceptibility".

2018-11-07T17: 00: 00-0500