An automated, scalable, and rapid AST system for Gonorrhea STIs

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Gonorrhea is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae (NG) that infects the urogenital, anorectal and pharyngeal tracts in humans. In 2018, there were an estimated 1.14M cases in the US, and 86.9M cases worldwide. Of concern is the growing incidence of antimicrobial resistance not only due to inappropriate use of antibiotics, but also because NG interacts with and acquires genetic material from other co-infections in the anatomical sites that it infects. This wide range of resistance mechanisms that NG isolates can potentially harbor makes it very challenging to develop rapid molecular methods of Antibiotic Susceptibility Testing (AST). Even among phenotypic AST methods, it has so far not been considered feasible to perform automated broth microdilution based ASTs on NG: principally because it is a fastidious organism in liquid culture. As a result, the primary method used to perform ASTs for NG is the manual agar dilution method, which (because it is so labor intensive) is currently conducted in only a very limited number of public health labs. Even these labs test only 200-300 samples a month. Acenxion Biosystems proposes to develop the first fully automated NG phenotypic AST platform that both satisfies the current CDC guidance for surveillance and fulfils an unmet clinical need for AST-guided “directed” antibiotic therapy. Our instrument will provide Minimum Inhibitory Concentration (MIC) and Susceptible/ Intermediate /Resistance (S/I/R) interpretation in < 6 hours with minimal sample preparation (<5 min per sample) at a reasonable price. The instrument will consist of stackable, cassette reader units with up to eight microfluidic cassette capacity; software/PC Controller; and single-use consumable (50-well microfluidic cassette pre-spotted with candidate antibiotics). Optimized broth and rapid stirring are employed for NG growth, enabling automated broth microdilution. With prior funding from the CDC, we have demonstrated proof-of-concept for the proposed instrument by building a partly-automated system to perform broth micro- dilution experiments on a single 16-well cassette, and used it monitor the growth (or lack thereof) of 3 NG strains (1 ATTC QC strain, and 2 AR isolate strains) in the presence of multiple candidate antibiotics with 100% sensitivity & specificity. We seek “Direct to Phase II” funds to expand this earlier work: build a fully automated instrument and test it against the CDC’s challenge AR bank panel of 50 clinical isolates (which span multiple resistance mechanisms and yield wide range of phenotypic responses). We chose this set of organisms in lieu of patient samples from 2 - 3 locations to ensure better chances of success in the real world. Our commercialization strategy aims to first bring efficiencies to the existing market (regional labs participating in the Gonococcal Isolate Survey Program) and then to expand the user (customer) base to hospital labs, clinical laboratory networks and clinical labs by enabling AST-guided directed antibiotic therapy for gonorrhea.