Section of Infectious Disease, Louisiana State University Health Sciences Center, New Orleans.
Desert AIDS Project, Palm Springs, California.
Clin Infect Dis. 2018 Aug 1;67(4):504-512. doi: 10.1093/cid/ciy145.
In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea.
Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4-8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin.
The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose.
This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea.
NCT02294682.
在这项 2 期研究中，我们评估了新型三氮杂萘并嘧啶类 II 型拓扑异构酶抑制剂口服格帕沙星治疗单纯性泌尿生殖系统淋病的疗效和安全性。
入组患有疑似泌尿生殖系统淋病的成年参与者，并完成基线（第 1 天）和治疗后（第 4-8 天）访视。采集泌尿生殖道拭子进行淋病奈瑟菌（NG）培养和药敏试验。如果有已知暴露史，则采集咽和直肠拭子标本。参与者按性别分层，1:1 随机接受 1500mg 或 3000mg 单剂量口服格帕沙星。
微生物学可评估人群包括 69 名参与者，NG 分别从 69 名（100%）泌尿生殖道、2 名（3%）咽和 3 名（4%）直肠标本中分离出来。NG 的微生物学清除率分别为 97%、95%和 96%（下侧 1 侧精确 95%置信区间下限分别为 85.1%、84.7%和 89.1%），分别为 1500mg、3000mg 和联合剂量组。69 例泌尿生殖道感染中有 66 例（96%）达到微生物学治愈。所有 3 例失败均为 NG 分离株，其表现出的最高观察到的格帕沙星最小抑菌浓度为 1µg/mL，并伴有常见的基因突变。在咽和直肠部位，分别有 1/2 和 3/3 的 NG 分离株达到微生物学治愈。两种剂量均无治疗相关不良事件。
本研究表明，单次口服格帕沙星剂量对成人单纯性泌尿生殖系统淋病的 NG 细菌清除率≥95%。
NCT02294682。
