• Resistance in Neisseria gonorrhoeae has emerged to the last treatment, ceftriaxone • We show a high zoliflodacin susceptibility among gonococci from three WHO Regions • We found two gonococcal isolates from Cambodia with increased zoliflodacin MICs • Our study supports the further development of zoliflodacin for gonorrhoea treatment Zoliflodacin, a novel spiropyrimidinetrione, showed non-inferiority compared to recommended ceftriaxone plus azithromycin treatment in a recent global phase 3 randomized controlled trial for gonorrhoea treatment. We evaluated the susceptibility of zoliflodacin among 2993 contemporary gonococcal isolates collected in 2021-2024 in eight World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme (WHO EGASP) countries in the WHO South-East Asian Region (Indonesia, Thailand), WHO Western Pacific Region (Cambodia, The Philippines, Viet Nam), and WHO African Region (Malawi, South Africa, Uganda). Minimum inhibitory concentrations (MICs) of zoliflodacin were determined using the agar dilution technique and the zoliflodacin target gene ( gyrB ) was examined with Illumina sequencing. Zoliflodacin exhibited high activity: MICs ranging from 0.001 to 1 mg/L and a modal MIC of 0.032 mg/L. The zoliflodacin MIC distribution showed mostly a wild-type profile, however, two isolates from Cambodia had MICs of 0.5 mg/L and 1 mg/L. Both these isolates also harboured the GyrB D429N mutation, associated with increased zoliflodacin MICs. We show a high zoliflodacin susceptibility internationally, including against ceftriaxone-resistant and azithromycin-resistant gonococcal strains. Our findings support the continued clinical development of zoliflodacin as a treatment for gonorrhoea, though cautious and monitored introduction and continuous international resistance surveillance are imperative.
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Jacobsson et al. (2025) studied this question.
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