The FC428 clone: tracking global transmission of drug-resistant gonorrhea

The emergence of Neisseria gonorrhoeae strains resistant to ceftriaxone, the last reliable treatment, poses significant public health threats. The global spread of the FC428 clone, carrying penA allele 60.001, is of particular concern due to its association with high-level ceftriaxone resistance and frequent treatment failures. The ability of these strains to transmit widely without significant biological fitness deficits underscores the urgent need for new therapeutic approaches to address this escalating challenge in sexually transmitted infection control.

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.

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

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.

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References

DOI

10.1097/IM9.0000000000000113

Original Source URL

https://doi.org/10.1097/IM9.0000000000000113

Funding information

This work was supported by the National Natural Science Foundation of China (grant numbers 82272382, 82150610507, 82072320, 81871695). The funder had no role in study design, data collection and interpretation, writing of the manuscript, or the decision to submit the manuscript for publication.

About Infectious Microbes & Diseases

Infectious Microbes & Diseases (IMD) is an international open-access peer-reviewed journal that is dedicated to accelerate the dissemination, exchange and utilization of basic, applied and clinical scientific research results related to the field of infectious microbes and infectious diseases. IMD provides rapid peer-review for articles. By utilizing the open-access model, IMD aims to contribute globally to the translation of basic research findings and the evaluation of current and novel treatments, into the promotion of optimal practices for diagnosis and treatment of infections to improve the public health. IMD strives for a rapid review process and only publishes manuscripts of outstanding quality. IMD provides a forum where all researchers, clinicians and policymakers can exchange their ideas and learn about the most accomplished and significant advances in the field.Infectious Microbes & Diseases (IMD) is jointly sponsored by Zhejiang University and the First Affiliated Hospital, school of Medicine, Zhejiang University​ and published by Wolters Kluwer and Zhejiang University Press.