Development of an impedance-based fast antimicrobial susceptibility test for Neisseria gonorrhoeae
Caitlin N Daniels1, Bethany K Martin1, Kazi S Nahar2
1Antimicrobial Discovery, Development and Diagnostics, Countermeasures Development, Evaluation and Preparedness Division, UK Health Security Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Objectives:
Antimicrobial-resistant Neisseria gonorrhoeae is a serious threat to global health. Current N. gonorrhoeae antimicrobial susceptibility testing (AST) is laborious and time consuming (≥2 days) leading to overprescription of last-resort, broad-spectrum antibiotics. In this proof-of-principle study, we developed a fast (<8 h) phenotypic, impedance-based AST for N. gonorrhoeae against frontline and experimental antibiotics.
Methods:
WHO N. gonorrhoeae reference strains F, K, O, V, X and Y were exposed to EUCAST susceptibility breakpoint concentrations of ceftriaxone, ciprofloxacin and azithromycin for up to 5 h and to doubling dilutions of antibiotics for 4 h. The % cell count of antibiotic exposed compared with unexposed control samples, as measured by an impedance-based Fast Antimicrobial Susceptibility Test (iFAST®), was used to differentiate between susceptible and non-susceptible strains. Responses to novel antimicrobial compounds, including zoliflodacin and gepotidacin, were also measured by iFAST® and compared with published MICs.
Results:
The protocol reported susceptibility profiles concordant with published data for all strain-drug combinations after 4 h of exposure. Dose-response curves generated using iFAST® for most strain-drug combinations were in essential agreement with published Etest MIC values. Novel compounds assessed using iFAST® showed higher antimicrobial activity than ciprofloxacin in the high-level resistant strain WHO X.
Conclusions:
iFAST® AST results were concordant with the current clinical standards and measured in under 8 h. This method is therefore promising for the development of a rapid and accurate phenotypic N. gonorrhoeae antimicrobial susceptibility test.
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