Suppr
超能文献

单次剂量唑利福霉素（ETX0914）治疗泌尿生殖系统淋病。

Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea.

机构信息

From the Louisiana State University Health Sciences Center, New Orleans (S.N.T.); University of Alabama at Birmingham, Birmingham (J. Marrazzo, E.W.H.); University of Washington, Seattle (J. Marrazzo); Indiana University, Indianapolis (B.E.B.); University of North Carolina, Chapel Hill (A.C.S.), and FHI 360, Durham (S.M.J.) - both in North Carolina; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Disease, Bethesda (J.L.), and Emmes, Rockville (M.R.W., H.K.) - both in Maryland; and Entasis Therapeutics, Waltham, MA (K.L., J. Mueller).

出版信息

N Engl J Med. 2018 Nov 8;379(19):1835-1845. doi: 10.1056/NEJMoa1706988.

DOI:10.1056/NEJMoa1706988

PMID:30403954

Abstract

BACKGROUND

Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.

METHODS

We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.

RESULTS

From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.

CONCLUSIONS

The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918 .).

摘要

背景

耐抗生素淋病奈瑟菌的出现促使新疗法的开发。唑氟沙星是一种新的抗生素，可抑制 DNA 合成。在这项多中心、2 期临床试验中，评估了唑氟沙星治疗单纯性淋病的效果。

方法

我们随机分配符合条件的男性和女性，这些人有单纯性泌尿生殖系淋病的症状或体征，或未经治疗的泌尿生殖系淋病，或在过去 14 天内与患有淋病的人有过性接触，让他们接受单次口服 2 克或 3 克唑氟沙星，或单次 500 毫克肌肉注射头孢曲松，比例约为 70:70:40。治疗后 6±2 天进行疗效评估，然后在治疗后 31±2 天进行安全性随访。主要疗效评估指标是微生物学意向治疗（micro-ITT）人群中泌尿生殖部位微生物学治愈的比例。

结果

2014 年 11 月至 2015 年 12 月，共纳入 179 名参与者（167 名男性和 12 名女性）。在可评估的 141 名 micro-ITT 人群参与者中，57 名（96%）接受 2 克唑氟沙星、56 名（96%）接受 3 克唑氟沙星、28 名（100%）接受头孢曲松的患者在泌尿生殖部位的微生物学得到治愈。所有 5 名接受 2 克唑氟沙星和 7 名接受 3 克唑氟沙星的直肠感染患者，以及所有 3 名接受头孢曲松的患者，所有直肠感染均治愈。8 名（50%）接受 2 克唑氟沙星、11 名（82%）接受 3 克唑氟沙星和 4 名（100%）接受头孢曲松的患者咽感染得到治愈。共报告了 84 例不良事件：24 例发生在接受 2 克唑氟沙星组，37 例发生在接受 3 克唑氟沙星组，23 例发生在接受头孢曲松组。根据研究者的评估，共有 21 例不良事件被认为与唑氟沙星有关，大多数胃肠道不良事件。