Abstract Background Zoliflodacin is an oral, single-dose antibiotic being developed for patients with uncomplicated gonorrhea, including those infected with multidrug-resistant strains. Zoliflodacin is a first-in-class spiropyrimidinetrione that inhibits bacterial DNA biosynthesis primarily through the GyrB subunit of DNA gyrase. In this study, the in vitro activity of zoliflodacin against Neisseria gonorrhoeae collected in the US during 2022 was measured to verify continued activity against contemporary clinical isolates. Methods A total of 123 N. gonorrhoeae isolates, provided by the US Centers for Disease Control and Prevention (CDC) as part of the CDC Gonococcal Isolate Surveillance Program (GISP), were tested for in vitro susceptibility to zoliflodacin and 8 comparators. Isolates originated from both males (79.7%) and females (20.3%) and mainly from urogenital body sites (92.7%). Minimum inhibitory concentrations (MICs) were determined using agar dilution according to CLSI guidelines (M07, 11th ed.). Results The zoliflodacin MIC50/90 values were 0.12/0.12 µg/mL (MIC range ≤0.008 – 0.25 µg/mL). Susceptibility to ceftriaxone and azithromycin was high at 100% and 97.6%, respectively. Conversely, 10% and 64% of isolates were susceptible to tetracycline and ciprofloxacin, respectively. Zoliflodacin maintained activity, with MIC90 of 0.12 µg/mL, against all 43 ciprofloxacin-resistant isolates and all 110 tetracycline-non-susceptible isolates, and an MIC range of 0.12 – 0.25 µg/mL against all 3 azithromycin-non-susceptible isolates. There was no difference in the zoliflodacin MIC90 for isolates from males and females. Conclusion For N. gonorrhoeae clinical isolates collected in the US during 2022, the zoliflodacin MIC50/90 and MIC range were consistent with the potency observed during 2020 and 2021 US surveillance studies and demonstrate activity against antibiotic-resistant isolates and clinical isolates from males and females. These data support the continued development of zoliflodacin for patients with uncomplicated gonorrhea. Disclosures Sarah McLeod, PhD, Innoviva Specialty Therpeutics: Employee|Innoviva Specialty Therpeutics: Stocks/Bonds (Public Company)
McLeod et al. (Thu,) studied this question.