Susanne Jacobsson , Thitima Cherdtrakulkiat , Daniel Golparian , Lon Say Heng , Irving Hoffman , Manuel C. Jamoralin Jr. , Francis Kakooza , Rossaphorn Kittiyaowamarn , Peter Kyambadde , Pham Thi Lan , Venessa Maseko , Mitch Matoga , Etienne Müller , Thuy Thi Phan Nguyen , Vichea Ouk , Daniel Schröder , Vivi Setiawaty , Sonia B. Sia , Verawati Sulaiman , Mot Virak , Magnus Unemo
{"title":"2021-2024年，在世卫组织3个区域的8个世卫组织强化淋球菌抗菌药物监测规划国家中，淋病奈瑟菌分离株对新型抗菌药物唑氟菌素高度敏感","authors":"Susanne Jacobsson , Thitima Cherdtrakulkiat , Daniel Golparian , Lon Say Heng , Irving Hoffman , Manuel C. Jamoralin Jr. , Francis Kakooza , Rossaphorn Kittiyaowamarn , Peter Kyambadde , Pham Thi Lan , Venessa Maseko , Mitch Matoga , Etienne Müller , Thuy Thi Phan Nguyen , Vichea Ouk , Daniel Schröder , Vivi Setiawaty , Sonia B. Sia , Verawati Sulaiman , Mot Virak , Magnus Unemo","doi":"10.1016/j.ijregi.2025.100624","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>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).</div></div><div><h3>Methods</h3><div>Minimum inhibitory concentrations (MICs) of zoliflodacin were determined using the agar dilution technique, and the zoliflodacin target gene (<em>gyrB</em>) was examined with Illumina sequencing.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":73335,"journal":{"name":"IJID regions","volume":"15 ","pages":"Article 100624"},"PeriodicalIF":1.5000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High susceptibility to the novel antimicrobial zoliflodacin among Neisseria gonorrhoeae isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021-2024\",\"authors\":\"Susanne Jacobsson , Thitima Cherdtrakulkiat , Daniel Golparian , Lon Say Heng , Irving Hoffman , Manuel C. Jamoralin Jr. , Francis Kakooza , Rossaphorn Kittiyaowamarn , Peter Kyambadde , Pham Thi Lan , Venessa Maseko , Mitch Matoga , Etienne Müller , Thuy Thi Phan Nguyen , Vichea Ouk , Daniel Schröder , Vivi Setiawaty , Sonia B. Sia , Verawati Sulaiman , Mot Virak , Magnus Unemo\",\"doi\":\"10.1016/j.ijregi.2025.100624\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><div>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).</div></div><div><h3>Methods</h3><div>Minimum inhibitory concentrations (MICs) of zoliflodacin were determined using the agar dilution technique, and the zoliflodacin target gene (<em>gyrB</em>) was examined with Illumina sequencing.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":73335,\"journal\":{\"name\":\"IJID regions\",\"volume\":\"15 \",\"pages\":\"Article 100624\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-03-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IJID regions\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772707625000591\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"IJID regions","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772707625000591","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
摘要
目的在最近进行的淋病治疗全球 III 期随机对照试验中，新型螺旋嘧啶三酮类药物唑来氟哌酸与推荐的头孢曲松加阿奇霉素治疗相比没有劣效。我们评估了 2021-2024 年在世界卫生组织（WHO）加强淋球菌抗菌药物监测计划的 8 个国家（WHO 东南亚地区（印度尼西亚、泰国）、WHO 西太平洋地区（柬埔寨、菲律宾、越南）和 WHO 非洲地区（马拉维、南非、乌干达）收集的 2993 例当代淋球菌分离株对唑力氟达嗪的药敏性。方法使用琼脂稀释技术测定佐利氟达星的最低抑菌浓度（MICs），并使用 Illumina 测序技术检测佐利氟达星的靶基因（gyrB）：其 MIC 为 0.001 至 1 毫克/升，平均 MIC 为 0.032 毫克/升。唑氟达星的 MIC 分布主要呈野生型分布；然而，来自柬埔寨的两个分离株的 MIC 为 0.5 毫克/升和 1 毫克/升。这些分离株还携带 GyrB D429N 突变，与佐利氟达星 MICs 增高有关。结论我们发现国际上对佐利氟达星的敏感性很高，包括对头孢曲松和阿奇霉素耐药淋球菌菌株的敏感性。我们的研究结果支持继续将唑来氟烷作为治疗淋病的药物进行临床开发，但必须谨慎、有监控地引入该药物并持续进行国际耐药性监测。
High susceptibility to the novel antimicrobial zoliflodacin among Neisseria gonorrhoeae 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 (gyrB) 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.
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