Emergence of FC428 clone and the global spread of ceftriaxone-resistant gonorrhea

Neisseria gonorrhoeae, responsible for the sexually transmitted infection gonorrhea, is becoming increasingly difficult to treat as the pathogen has developed resistance to multiple antibiotics. Historically, ceftriaxone has been the last line of defense, effectively treating both urogenital and pharyngeal infections. However, emerging high-level ceftriaxone-resistant strains, particularly those associated with the FC428 clone, threaten to render this treatment ineffective. Based on these challenges, there is a pressing need to study and develop alternative treatment options.

Researchers from Zhejiang University and other collaborators have published a review (DOI: 10.1097/IM9.0000000000000113) on January 23, 2023, in Infectious Microbes & Diseases, detailing the global transmission and treatment challenges associated with ceftriaxone-resistant gonorrhea. The study focuses on the FC428 gonococcal clone, which was first identified in Japan in 2015 and has spread globally, causing treatment failures in multiple countries. The clone's resistance is linked to the penA allele 60.001, necessitating new strategies to combat this public health threat.

The FC428 clone of Neisseria gonorrhoeae, identified in Japan in 2015, rapidly expanded across continents, affecting countries in Asia, Europe, and North America. This clone carries penA allele 60.001, conferring resistance to ceftriaxone with minimum inhibitory concentrations (MICs) often ranging from 0.5 to 1 mg/L. Unlike other resistance-conferring alleles, penA 60.001 does not significantly impair bacterial growth, contributing to the clone's successful global dissemination. Despite high-level resistance, some gonorrhea cases were resolved using increased doses (500 mg to 2 g) of ceftriaxone, sometimes combined with azithromycin. However, treatment failures have occurred, underscoring the need for new alternatives. Ertapenem has shown promise as a potential therapy, although additional clinical studies are needed to confirm its efficacy. The ongoing spread and limited impact on biological fitness highlight the clone's potential to challenge current therapeutic protocols.

The widespread transmission of the FC428 clone is alarming, as it challenges the efficacy of ceftriaxone-based treatments, our last reliable option against gonorrhea. The strain's minimal impact on fitness suggests that it may continue to spread unchecked, demanding urgent global surveillance and development of novel therapeutic strategies to curb this public health crisis."

Dr. Stijn van der Veen, leading microbiologist at Zhejiang University

The study underscores the pressing need for comprehensive surveillance and research into new antibiotics or combination therapies to manage drug-resistant gonorrhea. The emergence of the FC428 clone highlights vulnerabilities in current treatment paradigms and reinforces the necessity for healthcare systems to prepare for a future where ceftriaxone might no longer be effective. Continued investment in research and international collaboration is essential to prevent the widespread public health impact of an untreatable sexually transmitted infection.