New Insights into Ceftriaxone-Resistant Gonorrhea

More than 100 million people worldwide have been diagnosed with gonorrhea, a sexually transmitted infection (STI) that can cause infertility and increase the risk for HIV in those who suffer from the infection. In addition, it can be passed on to babies born to infected mothers.

Recently, there has been some sobering news regarding its treatment.

For years, the older-line antibiotic ceftriaxone has been among the few remaining viable treatments against Neisseria gonorrhoeae (N. gonorrhoeae), particularly when used in combination with azithromycin. Although resistant strains have been reported sporadically, in recent years, there have been no reports of what an international team of researchers has described as “sustained transmission”—until now.

Following up on landmark articles published out of Denmark and Canada, the authors of a new study published in the April 2018 issue of Emerging Infectious Diseases (EID) have described the spread of a ceftriaxone-resistant FC428 N. gonorrhea clone in Japan among heterosexual men traveling from Asia to Australia. They write that their findings “provide further evidence of international transmission of a ceftriaxone-resistant” strain.

“To date, there have only been a handful of reported cases involving ceftriaxone-resistant gonorrhea strains,” study co-author David Whiley, PhD, principal research fellow, Microbial Diagnostics and Characterization Group, UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia, told Contagion^®. “Therefore, ceftriaxone-resistant strains remain rare, and currently there is no reason to start rethinking the use ceftriaxone. However, physicians should be mindful that such strains exist, and that it is theoretically possible that a patient could fail ceftriaxone therapy. If a doctor suspects that a patient has failed ceftriaxone therapy, then appropriate samples should be taken so that a laboratory can test the strain for resistance. On a global scale, I think more could be done to ensure sufficient numbers of gonorrhea strains are being tested for resistance, as I am sure there is a lot more resistance out there that simply isn’t being detected because surveillance is quite limited in many regions.”

Increased understanding of treatment-resistant N. gonorrhea has become even more vital in light of news out of the United Kingdom, reported by Contagion^® on April 5, that a male patient there has been diagnosed by an isolate of the STI that is resistant to all first-line treatment. According to a comment on the patient published on March 29 in Volume 12, Issue 11 of Health Protection Report, an official publication of Public Health England, the patient was infected with the isolate, which is resistant to both ceftriaxone and azithromycin, while traveling abroad.

For the EID study, Dr. Whiley and his colleagues, including epidemiologists and other specialists affiliated with the World Health Organization (WHO), performed “bioinformatic analyses” that included core single-nucleotide variation phylogeny and in silico molecular typing. Their phylogenetic analysis of 5 isolates ceftriaxone-resistant FC428 N. gonorrhoeae revealed that they shared “close genetic relatedness,” including multilocus sequence type 1903; sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), which have been associated with ceftriaxone resistance.

“There was nothing clinically that made us suspect these patients had a gonorrhea strain that was different any other,” Dr. Whiley explained. “The surprise came when we assessed the strains in the laboratory and determined, based on a laboratory measure of resistance, that these strains exhibited resistance to ceftriaxone. This highlights the importance of laboratory surveillance, so we know what resistant strains are circulating in the community and so we can ensure treatments remain suitable. If ceftriaxone-resistant gonorrhea strains become widespread then it will become very difficult to manage [the disease].”

The troubling findings out of Australia and Asia follow on the heels of new research, also out of Australia, that describes a “gonorrhea superbug” that can evade the human immune response by creating microscopic bacterial membrane bubbles or “blebs” that cause macrophages to die in an “orchestrated suicide.” Study co-author Thomas Naderer, PhD, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia, said in a statement released with the findings that he and his team hope that their new understanding of the mechanism of gonorrhea “may lead to strategies to combat [the disease] and its symptoms.”

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.