Developing the Gepotidacin 10µg Disc: Advancing Antimicrobial Susceptibility Testing
Gepotidacin is the first agent in a new class of type IIA topoisomerase inhibitors. There are two types of bacterial IIA topoisomerases, DNA gyrase and topoisomerase IV. Gepotidacin is a novel triazaacenaphthylene bactericidal antibiotic, which works by blocking topoisomerase IV and the B subunit of DNA gyrase, which inhibits DNA replication.
As a broad-spectrum oral antibiotic with a unique mechanism of action, gepotidacin has demonstrated activity against many clinically significant pathogens, including Staphylococcus saprophyticus, Enterococcus faecalis, Neisseria gonorrhoeae and multidrug-resistant Escherichia coli.
Being the first new type of oral antibiotic to treat uncomplicated urinary tract infections (uUTIs) to be approved in nearly three decades, gepotidacin provides a new treatment option for women facing uUTIs and is also indicated in the USA as therapy for adults with uncomplicated urogenital gonorrhoea.
Gepotidacin differs from current antibiotics which also target gyrase and topoisomerase IV in the way it binds to an independent structural protein pocket and by promoting stable single-stranded DNA breaks. This allows gepotidacin to retain efficacy against DNA gyrase and topoisomerase IV that contain the most common fluoroquinolone-resistance mutations.
The addition of Gepotidacin 10µg antimicrobial susceptibility test (AST) discs to the MASTDISCS® range of represents another milestone in Mast's commitment to supporting advances in antimicrobial susceptibility testing.
Introducing AST discs for newly licensed antimicrobials is a critical step in enabling laboratories to rapidly implement testing following regulatory approval of the compound. By expanding the MASTDISCS® portfolio to include Gepotidacin 10µg, Mast ensures laboratories have access to reliable susceptibility testing solutions that support timely clinical decision-making.
Every new antimicrobial presents unique IVD development challenges, the development process of an IVD device is complex, expensive and time-consuming. Adapting an automated AST device to accommodate a new drug is a lengthier process than the development of manual tests, making manual devices such as discs the first option for susceptibility testing of new compounds.
Mast’s involvement with gepotidacin began in 2012, when as part of the mastpharma® service we collaborated alongside a pharmaceutical sponsor and developed an antimicrobial susceptibility testing disc containing gepotidacin.
Disc potency, antimicrobial stability, diffusion characteristics and performance all require careful optimisation before a product reaches the end user laboratory for routine use. The Gepotidacin MASTDISC® has been developed using Mast's almost 70 years of expertise in AST disc manufacture, ensuring laboratories receive a product that delivers the consistency and reliability they expect.
Initial development of the disc proved especially challenging given the wide panel of possible target organisms. Performance of the disc was initially optimised to Clinical & Laboratory Standards Institute (CLSI) methodology and focused on non-fastidious Gram positive and Gram-negative organisms involved in uUTIs, this was then expanded to include European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and fastidious organisms such as Neisseria gonorrhoea.
The inclusion of uncomplicated urogenital gonorrhoea indication and Neisseria gonorrhoea as a target brought about a different set of challenges, primarily due to the scarcity of commercially available test media and supplements detailed in the CLSI methodology. This limitation had the potential to hinder the ability to evaluate the disc performance against Neisseria gonorrhoea isolates on media from different manufacturers. To address this challenge, the required media was prepared in-house.
There is currently no EUCAST disc diffusion test method for susceptibility testing of Neisseria gonorrhoea which also narrowed the approaches available for evaluating disc performance.
The resulting Gepotidacin 10µg Research Use Only disc was used in a variety of studies, including studies to generate quality control criteria published by CLSI and as part of surveillance testing.
As gepotidacin moved along the pharma development pipeline, Mast AST discs accompanied the compound through its phase 3 EAGLE-2 and EAGLE-3 outpatient uUTI trials as well as the uncomplicated urogenital gonorrhoea EAGLE-1 trial. Phase 3 trials are large, multi-centre studies which provide safety and efficacy data for a new drug compared to standard treatment. Data from these studies was used to support the registration of Gepotidacin to the FDA and MHRA.
The introduction of gepotidacin marks another important step in addressing antimicrobial resistance to established antibiotics and expanding treatment options for resistant bacterial infections. As new antibiotics continue to emerge, reliable antimicrobial susceptibility testing will remain fundamental to ensuring these therapies are used appropriately and effectively.
The Mast Gepotidacin 10µg AST disc represents more than the addition of another product to the portfolio. It demonstrates Mast's ongoing commitment to innovation, scientific excellence and collaborative partnership with pharmaceutical companies, CLSI, EUCAST and Contract Research Organisations (CROs) developing the next generation of antimicrobial therapies.
By combining decades of expertise in AST development with comprehensive technical support and long-term collaboration, Mast continues to help bridge the gap between pharmaceutical innovation and clinical laboratory implementation. Together through partnerships, Mast supports the successful introduction of new antimicrobials into IVD devices. Thereby supporting clinical scientist to improve patient care and contributing to the global effort to combat antimicrobial resistance.
As the landscape of infectious disease continues to evolve, Mast remains committed to providing not only high-quality diagnostic products but also the scientific expertise, collaborative partnerships and customer support needed to help shape the future of antimicrobial susceptibility testing.