High susceptibility to the novel antimicrobial zoliflodacin among isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021-2024.

OBJECTIVES

Zoliflodacin, a novel spiropyrimidinetrione, showed non-inferiority compared with recommended ceftriaxone plus azithromycin treatment in a recent global phase III randomized controlled trial for gonorrhea treatment. We evaluated the susceptibility of zoliflodacin among 2993 contemporary gonococcal isolates collected in 2021-2024 in eight World Health Organization (WHO) Enhanced Gonococcal Antimicrobial Surveillance Programme countries in the WHO Southeast Asian Region (Indonesia, Thailand), WHO Western Pacific Region (Cambodia, the Philippines, Viet Nam), and WHO African Region (Malawi, South Africa, Uganda).

METHODS

Minimum inhibitory concentrations (MICs) of zoliflodacin were determined using the agar dilution technique, and the zoliflodacin target gene () was examined with Illumina sequencing.

RESULTS

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. These isolates also harbored the GyrB D429N mutation, associated with increased zoliflodacin MICs.

CONCLUSIONS

We show a high susceptibility to zoliflodacin internationally, including against ceftriaxone- and azithromycin-resistant gonococcal strains. Our findings support the continued clinical development of zoliflodacin as a treatment for gonorrhea, although cautious and monitored introduction and continuous international resistance surveillance are imperative.