Activity of the novel oral antimicrobials zoliflodacin and gepotidacin against ceftriaxone-resistant and/or multidrug-resistant Neisseria gonorrhoeae isolates from Hangzhou, China.

Authors

Wenyan Lu, Ying Fu, Xu'ai Lin, Yuefeng Rao, Magnus Unemo, Stijn van der Veen

Published in

The Journal of antimicrobial chemotherapy. Volume 81. Issue 10. Sep 01, 2026.

Abstract

The emergence of ceftriaxone-resistant Neisseria gonorrhoeae threatens the effectiveness of this last-line empirical therapy for gonorrhoea. Zoliflodacin and gepotidacin are novel oral gyrase/topoisomerase inhibitors with distinct mechanisms of action, recently US FDA-approved for treatment of uncomplicated urogenital gonorrhoea. We evaluated their in vitro activity against contemporary multidrug-resistant N. gonorrhoeae isolates from Hangzhou, China, a region with high ceftriaxone resistance.
MICs of zoliflodacin and gepotidacin were determined by agar dilution for 340 clinical N. gonorrhoeae isolates collected in Hangzhou (2020-2025). Sequencing of gyrA, parC and gyrB quinolone resistance-determining regions (QRDRs) was performed.
All isolates were ciprofloxacin-resistant, and 23.2% were ceftriaxone-resistant. Zoliflodacin demonstrated potent activity (MIC range, 0.008-0.25 mg/L; MIC90, 0.06 mg/L). No isolate carried known GyrB target substitutions associated with increased zoliflodacin MICs (in D429 or K450), but GyrA S91F/D95G with ParC S87R was associated with slightly higher zoliflodacin wild-type MICs (P = 0.0004). Gepotidacin MICs ranged from 0.06 mg/L to 4 mg/L (MIC90, 2 mg/L); 42 isolates (12.4%) had non-susceptible MICs ≥2 mg/L. GyrA S91F/D95Y with ParC S87N and GyrA S91F/D95A with ParC D86N were associated with slightly higher gepotidacin MICs (P < 0.0001). No Spearman's rank correlation was observed between ciprofloxacin and zoliflodacin (R = 0.059) or gepotidacin (R = 0.0077) MICs.
Zoliflodacin demonstrated potent in vitro activity and all isolates in this high-ceftriaxone-resistance setting were categorized as susceptible. Gepotidacin also showed potent activity, but 12% of isolates displayed non-susceptible MICs (≥2 mg/L). Continuous surveillance (phenotypic and genomic susceptibility) is essential when these two novel oral therapies enter clinical practice.

PMID:
42809459
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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