The Journal of antimicrobial chemotherapy · 2026
Activity of the novel oral antimicrobials zoliflodacin and gepotidacin against ceftriaxone-resistant and/or multidrug-resistant Neisseria gonorrhoeae isolates from Hangzhou, China.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lu Wenyan, Fu Ying, Lin Xu'ai, Rao Yuefeng, Unemo Magnus, van der Veen Stijn
Аннотация
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.