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

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

Neisseria gonorrhoeaeresponsible for the sexually transmitted infection gonorrhea, is becoming increasingly difficult to treat as the pathogen has developed resistance to several antibiotics. Historically, ceftriaxone was the last line of defense and effectively treated both genitourinary and throat infections. However, there is a risk that this treatment may be rendered ineffective by emerging highly ceftriaxone-resistant strains, particularly those associated with the FC428 clone. Because of these challenges, there is an urgent need to investigate and develop alternative treatment options.

Zhejiang University researchers and other collaborators published a review (DOI: 10.1097/IM9.0000000000000113) on January 23, 2023Infectious microbes and diseasesdetailing the global transmission and treatment challenges associated with ceftriaxone-resistant gonorrhea. The study focuses on the gonococcal clone FC428, which was first identified in Japan in 2015 and has spread worldwide, leading to treatment failures in several countries. The resistance of the clone is related to thePenAallele 60,001, requiring new strategies to combat this public health threat.

The FC428 clone fromNeisseria gonorrhoeaeDiscovered in Japan in 2015, it quickly spread across continents, affecting countries in Asia, Europe and North America. This clone carriesPenAAllele 60,001, which confers resistance to ceftriaxone with minimum inhibitory concentrations (MICs) often between 0.5 and 1 mg/L. Unlike other alleles that confer resistancePenA60,001 does not significantly affect bacterial growth and thus contributes to the successful global spread of the clone. Despite high resistance, some cases of gonorrhea have been resolved with increased doses (500 mg to 2 g) of ceftriaxone, sometimes in combination with azithromycin. However, treatment errors have occurred, highlighting the need for new alternatives. Ertapenem has shown promise as a potential therapy, although further clinical trials are needed to confirm its effectiveness. 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 because it calls into question the effectiveness of ceftriaxone-based treatments, our last reliable option against gonorrhea. The strain's minimal impact on fitness suggests that it may continue to spread uncontrollably, requiring urgent global surveillance and development of novel therapeutic strategies to contain this public health crisis."

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

The study highlights the urgent need for comprehensive surveillance and research into new antibiotics or combination therapies to treat drug-resistant gonorrhea. The emergence of the FC428 clone highlights weaknesses in current treatment paradigms and underscores the need for healthcare systems to prepare for a future in which ceftriaxone may 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.

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