Single-Dose Zoliflodacin for the Treatment of Urogenital Gonorrhea
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.
METHODS
We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.
RESULTS
From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.
CONCLUSIONS
The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections.
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Additional Info
Disclosure statements are available on the authors' profiles:
Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea
N. Engl. J. Med 2018 Nov 08;379(19)1835-1845, SN Taylor, J Marrazzo, BE Batteiger, EW Hook, AC Seña, J Long, MR Wierzbicki, H Kwak, SM Johnson, K Lawrence, J MuellerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Oral Antibiotic for Gonorrhea?
Urogenital infections due to Neisseria gonorrhoeae (GC) have increased dramatically in the US. This is likely due to chronic underfunding of STI clinics/public health departments and issues associated with poor access to care for those at high risk for GC. Moreover, resistance to the standard macrolide and cephalosporin treatments presents an ever-increasing challenge. Consequently, the current recommendation for treatment of GC is as follows:
“CDC recommends dual therapy, or using two drugs, to treat gonorrhea – a single dose of 250 mg of intramuscular ceftriaxone AND 1g of oral azithromycin.”1
An investigational oral antibiotic, zoliflodacin, offers a promising alternative to current therapy. This antimicrobial is being fast tracked by the FDA and has a novel mechanism of action by interfering with DNA biosynthesis. A multicenter, phase II study, reported by Taylor et al., compared a single 2 g or 3 g oral dose of zoliflodacin with a 500 mg intramuscular dose of ceftriaxone for microbiologic cure of uncomplicated urogenital GC (it should be noted that the ceftriaxone dose was double the CDC recommendation). Secondary outcomes included cures for rectal and pharyngeal GC and safety. Subjects, aged 18 to 55 years, were recruited from five sexual health clinics and were predominantly male.
In the intent-to-treat population, the microbiological cure rates for urogenital GC were 96% for both 2 g and 3 g dosing of zoliflodacin, and 100% for IM ceftriaxone. All cases of rectal GC were cured. Results for pharyngeal infections were not as impressive, with 50% cure using 2 g, and 82% with 3 g of zoliflodacin, as compared with 100% for ceftriaxone. Adverse effects were primarily gastrointestinal and were at reasonable levels. Of note were the relatively high rates of penicillin, ciprofloxacin, and azithromycin antimicrobial resistance for GC isolates from the subjects.
Phase III testing is needed as well as development of protocols to assess effects of dual therapies such as zoliflodacin plus azithromycin. Nevertheless, a fully oral option for GC treatment could revolutionize and simplify care of STI patients and improve public health practice.
References
1. Centers for Disease Control and Prevention. Gonorrhea treatment and care. Accessed on 11/20/2018 Available at: https://www.cdc.gov/std/gonorrhea/treatment.htm.