As resistance, and incidence, are both on the rise, new options may come not a moment too soon.
Edward W. Hook III, MD, Endowed Professor of Infectious Disease Translational Research, departments of medicine, epidemiology and microbiology, at the University of Alabama-Birmingham, believes the drug zoliflodacin “is the most promising new antimicrobial for gonorrhea treatment we have had in nearly 20 years.”
He should know. He and his colleagues recently published the results of a phase 2 study, on November 8, 2018, in the New England Journal of Medicine, that concluded the novel drug was efficacious in “the majority of uncomplicated urogenital and rectal gonococcal infections” evaluated. The findings were notable because, as a related commentary published in the same issue of the journal highlights, gonorrhea is the second most commonly reported infection in the United States, and incidence has been on the rise since 2009.
“The problem of antibiotic-resistant gonorrhea is a threat and an emerging problem,” Dr. Hook told Contagion®. “Currently recommended therapy using a combination of ceftriaxone and azithromycin is highly effective, curing over 95% of uncomplicated gonorrhea. [However, there is a] lack of alternative antibiotics for persons who cannot take the currently recommended therapy and the future problem of the threat of untreatable gonorrhea due to the inexorably continuing development of antibiotic resistance by the organism.”
Indeed, the US Centers for Disease Control and Prevention (CDC), which supports the use of the aforementioned preferred treatment, reports that, in 2017, there were a total of 555,608 cases of gonorrhea in the United States, the highest since 1991 and an 18.6% increase over 2016. According to Dr. Hook, as with other infectious diseases, “antibiotic overuse” has contributed to “the continued development of resistance” in gonorrhea—meaning, that these infectious likely will become increasingly difficult to treat.
Enter zoliflodacin. For their research, Dr. Hook and his colleagues enrolled 179 adults between November 2014 and December 2015 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. Among the 141 participants in the micro intent-to-treat 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, all 7 who received 3 g of zoliflodacin, and in all 3 participants that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants who received 2 g of zoliflodacin, 9 of 11 participants who received 3 g of zoliflodacin, and 4 of 4 who received ceftriaxone.
Of note, though, 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. Of these, 21 were thought to be linked to zoliflodacin, and most were gastrointestinal-related.
Dr. Hook emphasized that further studies of the drug are needed, and are in the planning stages. In fact, a phase 3 study, led by Global Antibiotic Research and Development Partnership is scheduled to start in the coming months.
The authors of the journal commentary, Susan Blank, MD, MPH, and Demetre C. Daskalakis, MD, MPH, of the New York City Department of Health and Mental Hygiene, wrote, “Though the study was small, the efficacy shown is encouraging, and zoliflodacin has the potential to be an effective antibiotic for treating gonorrhea. In parallel with ongoing work to develop and approve new drugs, we need to develop point-of-care molecular diagnostics that permit rapid diagnosis of gonorrhea with real-time assessment of antimicrobial susceptibility in order to allow targeted therapy rather than empirical treatment that may be inadequate in the context of increasing antibiotic resistance. With more dedicated research on sexually transmitted infections to advance biomedical innovation and develop better diagnostics, therapeutics, and even vaccines, we may be able to avoid the advent of gonorrhea that is either treatable only with expensive intravenous or intramuscular agents or entirely untreatable.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous health care-related publications. He is the former editor of Infectious Disease Special Edition.