Novel Diagnostic Kit Enables Resistance-Guided Therapy for Gonorrhea

Updated treatment guidelines and the availability of the ResistancePlus GC test for Neisseria gonorrhoeae, from SpeeDx Inc, Sydney, Australia, are making it possible for some UK patients with gonorrhea to be treated with the cheap and easily-administered oral antibiotic ciprofloxacin. 

 
Ciprofloxacin was the first-line antibiotic of choice for uncomplicated gonorrhea in the past, but it was relegated to use as an alternative treatment due to increasing resistance. The ResistancePlus GC test is a novel molecular diagnostic and antimicrobial susceptibility test that can simultaneously diagnose gonorrhea and provide information about whether a patient will respond to ciprofloxacin.¹ 
 
The incidence of sexually transmitted infections (STIs), including gonorrhea, is increasing around the world, with correspondingly increasing rates of resistance to commonly used antibiotics. The first two cases of multidrug-resistant N. gonorrhoeae were reported in the UK at the start of 2019. These followed the first globally reported case of gonorrhea with high-level resistance to azithromycin and resistance to ceftriaxone in England in 2018.² 
 
Global management strategies for antimicrobial resistance, such as those developed by the World Health Organization, identify management of gonorrhea infection as a high priority, with more-effective use of diagnostic tools listed as a key focus for future development.³ 
 
“As a clinician, I would like to treat as many gonococcal infections with ciprofloxacin as possible,” says John White, MD, consultant in sexual health and HIV at the Altnagelvin Hospital and editor-in-chief of the International Journal of STDs & AIDS. “More than ever, we rely on accurate and patient-focused diagnostic strategies to detect and treat STIs.” 
 
Availability of the ResistancePlus GC test is timely, as the British Association of Sexual Health and HIV (BASHH) has launched its 2019 gonorrhea management guidelines, which include the use of ciprofloxacin, provided antimicrobial susceptibility results are available prior to treatment.⁴ 
 
The new test could be critical in the battle against antibiotic resistance, helping physicians to prescribe an effective antibiotic using a resistance-guided approach. Prior to the 2019 BASHH guidelines, the recommended front-line treatment for gonorrhea was ceftriaxone together with azithromycin. Ce ftriaxone is a painful intramuscular injection. It has long been considered the last readily available effective antibiotic for gonorrhea. But researchers have now isolated several strains of N. gonorrhoeae that exhibit extensive drug resistance to ceftriaxone and many other available treatments.^5,6 

“The new guideline now recommends giving double the previously recommended dose of ceftriaxone (now 1g stat),” says White. “However, they also indicate ciprofloxacin as a first-line option when antimicrobial susceptibility is known prior to treatment.”⁴ 
 
Such treatment is less painful for patients and is also preferred by doctors, as it is a cheaper treatment that does not require specialized staff to administer the injection.⁷ 
 
“If we can use less ceftriaxone this may also help to stall the further development and dissemination of ceftriaxone-resistant strains within Europe,” White adds. 
 
As the UK now has the lowest reported rate of ciprofloxacin-resistant gonorrhea (26%), more than 70% of patients could now benefit from the new guidelines and receive oral therapy if they have a test result showing ciprofloxacin susceptibility, such as is offered by the ResistancePlus GC test. 
 
ResistancePlus GC was invented by scientists in Australia and is now able to be accessed by clinicians in the UK. It is the first commercially available molecular diagnostic to provide ciprofloxacin susceptibility information, and it is well placed to support current laboratory molecular testing workflows. Currently, culture methods are the routine tests required to determine antimicrobial susceptibility, but it can take days for such tests to produce results, and many rectal (50%) and the majority of throat (70%) samples can be difficult to culture. ResistancePlus GC can overcome these limitations. 
 
“We are fortunate here in Europe that most of these infections can potentially be treated with ciprofloxacin, using the principles of resistance-guided therapy, provided we have access to accurate and timely resistance information, which is provided by the ResistancePlus GC assay,” says White. “It’s great to see novel molecular diagnostics moving beyond just binary positive/negative capability, providing results that help manage patients more effectively by enabling tailored treatment.” 
 
Treating gonorrhea as soon as possible is very important because gonorrhoea can lead to serious long-term health problems. Among women such health issues can include pelvic inflammatory disease that may result in infertility. Among men, problems can include infection of the testicles.⁸ 
 
Recent studies suggest that N. gonorrhoeae is threatening to become untreatable, as resistance continues to develop against all known antimicrobials.⁹ Gonorrhea is the second most common bacterial sexually transmitted infection (STI) in the UK, after chlamydia. In 2017, more than 44,676 people were diagnosed with gonorrhea in England, representing a 22% increase compared to the previous year.⁴ 
 
SpeeDx received the CE mark for the ResistancePlus GC assay at the end of 2018, enabling it to be adopted in all countries where the CE mark is accepted, including the UK. The test is based on the company’s proprietary PlexPCR method that detects both N. gonorrhoeae and sequences in the gyrA gene of the bacteria associated with susceptibility to ciprofloxacin. 
“SpeeDx is proud to have pioneered the development of the new ResistancePlus GC test, which should make a big difference for patients with gonorrhea,” says Colin Denver, CEO of SpeeDx. “We already successfully developed and launched a number of diagnostic tests for sexually transmitted diseases, including the ResistancePlus MG test launched last year for the detection of Mycoplasma genitalium and resistance to macrolide antibiotics.” 

For more inf on the diagnostic kits, visit SpeeDx at : https://plexpcr.com/

References 

1. Trembizki E, Guy R, Donovan B, et al. Further evidence to support the individualized treatment of gonorrhea with ciprofloxacin. Lancet Infect Dis.2016;16(9):1005–1006; doi: 10.1016/S1473-3099(16)30271-7. 
2. Multidrug Resistant Gonorrhea in England: 2018 [online]. London: Public Health England, 2018. Available at: www.gov.uk/government/publications/multi-drug-resistant-gonorrhoea-in-england-2018. Accessed January 29, 2019. 
3. Rapid Risk Assessment: Extensively Drug-Resistant (XDR) Neisseria gonorrhoeae in the United Kingdom and Australia [online]. Solna, Sweden: European Center for Disease Prevention and Control, 2018. Available at: https://ecdc.europa.eu/en/publications-data/rapid-risk-assessment-extensively-drug-resistant-xdr-neisseria-gonorrhoeae-united. Accessed January 29, 2019. 
4. Fifer H, Saunders J, Soni S, Sadiq ST, FitzGerald M. British Association for Sexual Health and HIV National Guideline for the Management of Infection with Neisseria gonorrhoeae [online]. Macclesfield, Cheshire, UK: British Association for Sexual Health and HIV, 2019. Available at: www.bashhguidelines.org/media/1208/gc-2019.pdf. Accessed January 29,2019. 
5. UK case of Neisseria gonorrhoeae with high-level resistance to azithromycin and resistance to ceftriaxone acquired abroad [online]. Public Health England Health Protection Report. 2018;12(11). Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/694655/hpr1118_mdrgc.pdf. Accessed January 29, 2019. 
6. Multidrug resistant gonorrhea [media release, online]. Canberra, ACT, Australia: Australian Government Department of Health, 2018. Available at: https://beta.health.gov.au/news-and-events/media-releases/multi-drug-resistant-gonorrhoea. Accessed January 29, 2019. 
7. Van Amerongen R, Gazendam RP, van Bergen JEAM. Trends in antimicrobial management of gonorrhea by general practitioners in Amsterdam, the Netherlands, between 2010 and 2016: a cross-sectional study. BMC Fam Pract. 2019;20:12; doi: 10.1186/s12875-018-0900-9. 
8. Gonorrhoea Complications [online]. London: National Health Service, 2018. Available at: www.nhs.uk/conditions/gonorrhoea/complications. Accessed January 29, 2019. 
9. Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. Nat Rev Urol.2017;14(3):139–152; doi: 10.1038/nrurol.2016.268.