近日，瑞士全球抗生素研究与开发伙伴关系Alison Luckey团队研究了唑氟达星与头孢曲松联合阿奇霉素治疗无并发症泌尿生殖道淋病的疗效比较。相关论文于2025年12月13日发表在《柳叶刀》杂志上。

开发新的淋病治疗方法是全球公共卫生的一项重点。研究组旨在评价唑氟达星与头孢曲松加阿奇霉素治疗无并发症泌尿生殖系统淋病的疗效和安全性。

在这项多国、随机、对照、开放标签、非劣效性的3期临床试验中，年龄在12岁及以上、临床怀疑患有无并发症泌尿生殖器淋病的受试者符合入选条件。该试验在比利时、荷兰、南非、泰国和美国的17家门诊诊所进行。确定疾病流行率高的参与国参与研究。选择参与的地点由具有研究经验的主要研究人员领导，他们对艾滋病毒或性传播感染和治疗非常了解。可行性调查问卷和研究前访问评估了性传播感染病例管理指南、临床服务和资源（即设施、工作人员、研究小组的拟议组成、现场提供的标准性传播感染服务、实验室能力评估、研究经验和临床试验的伦理审查）。符合条件的参与者被随机分配（2:1）接受单剂量唑氟达星3g（口服）或头孢曲松500 mg（肌肉注射）加阿奇霉素1g（口服）。参与者和治疗他们的临床医生都知道治疗分配；但是，微生物实验室的工作人员和赞助商的中心研究小组不知情，直到数据库锁定后。主要终点是微生物意向治疗人群中在治愈测试（TOC；第6± 2天）中微生物治愈（根除淋病奈瑟菌，通过尿道或宫颈内培养确定）的患者比例。如果治疗差异的双侧95%置信区间上限（比较药物减去唑氟达秦）低于12%的非劣效性界限，则主要疗效分析宣布非劣效。

2019年11月6日至2023年3月16日期间，1011名患者接受了筛查。81名患者不符合筛查标准，930名参与者随机分配到唑氟达星组（n=621）或比较药组（n=309）。参与者平均年龄为29.7岁（SD 9.4）。930名参与者中有815名（88%）在出生时被指定为男性，115名（12%）在出生时被指定为女性。930名参与者中有514名（55%）是黑人或非裔美国人，285名（31%）是亚洲人，113名（12%）是白人。在微生物意向治疗（泌尿生殖系统）人群（主要疗效终点）中，506名唑氟达星组的TOC微生物治愈率为460 (90.9%)，238名比较组的TOC微生物治愈率为229（96.2%）。组间估计差异为5.3% (95% CI为1.4 - 8.6)，置信区间上限在预定的非劣效性范围内，小于12%。唑氟达星总体耐受良好，治疗组间不良事件相似。最常见的治疗不良事件包括唑氟达星组的头痛（619例患者中61例[10%]）、中性粒细胞减少（42例[7%]）和白细胞减少（24例[4%]），比较组的注射部位疼痛（308例患者中38例[12%]）、中性粒细胞减少（24例[8%]）和腹泻（22例[7%]）。大多数不良事件的严重程度为轻度或中度。无严重不良事件报告。

研究结果表明，唑氟达星在治疗无并发症的泌尿生殖淋病方面不逊于头孢曲松加阿奇霉素，且具有相似的安全性。这些数据表明，唑氟达星作为一种有效的口服治疗方案，对于无并发症的泌尿生殖器淋病具有潜在的作用。

附：英文原文

Title: Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial

Author: Alison Luckey, Manica Balasegaram, Lindley A Barbee, Teresa A Batteiger, Helen Broadhurst, Stephanie E Cohen, Sinead Delany-Moretlwe, Henry J C de Vries, Jodie A Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P Mueller, Vimla Naicker, Seamus OBrien, John P ODonnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N Taylor, Magnus Unemo, Zinhle Zwane, Edward W Hook, Keisha De Gouveia, Thembisa Makowa Mkhize, Samantha Siva, Lindy Gumede, Ranmini Kularatne, Venessa Maseko, Shabashini Reddy, Patience Kwedza, Ravesh Singh, Lisha Sookan, Danielle Travill, Kittipoom Chinhiran, Sarinthorn Mongkolrat, Chatnapa Duangdee, Jantawan Satayarak, Siriporn Nonenoy, Supanat Thitipatarakorn, Joseph V Woodring, Wannee Chonwattana, Supawadee Na-pompet, Waropart Pongchaisit, Suwan Sriviriyakul, Tanyaporn Wansom, Aaron Ermel, Lora Fortenberry, Catherine L Cammarata, Rebecca Lillis, Alison Cohee, Ejovwoke Dosunmu, Godfred Masinde, Paula Dixon, Julia C Dombrowski, Olusegun O Soge, Elske Hoornenborg, Alje van Dam, Vicky Cuylaerts, Irith Debaetselier, Angèle Gayet-Ageron, Sarah M. McLeod, Alita Miller, Sarah Cohen, Hilary Johnstone, Lebogang Tshehla, Emilie Alirol, Carmen Au, Cherine Bajjali, Esther Bettiol, Pierre Daram, Amalia Droal, Varalakshmi Elango, Christophe Escot, Markus Heep, Karin Hergarden, Daniel Iniguez, Gabrielle Kornmann, Jean-Franois Louvion, Manon Manuelli, Jessica Renaux, Mary-Ann Richardson

Issue&Volume: 2025-12-11

Abstract:

Background

Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea.

Methods

In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by principal investigators with research experience, who were knowledgeable in HIV or sexually transmitted infections and treatment. Feasibility questionnaires and prestudy visits assessed sexually transmitted infection case management guidelines, clinical services, and resources (ie, facility, staff, proposed composition of the study team, standard sexually transmitted infection services offered at the site, assessment of laboratory capacity, research experience and ethical review of clinical trials). Eligible participants were randomly assigned (2:1) to receive a single dose of zoliflodacin 3 g (oral) or ceftriaxone 500 mg (intramuscular) plus azithromycin 1 g (oral). Treatment assignment was known to the participants and their treating clinicians; however, microbiology laboratory staff were masked and the sponsor's central study team were masked until after database lock. The primary endpoint was the proportion of patients with microbiological cure (eradication of Neisseria gonorrhoeae, determined by urethral or endocervical culture) at test of cure (TOC; day 6±2) in the microbiological intention-to-treat population. The primary efficacy analysis declared non-inferiority if the upper bound of the two-sided 95% CI for the treatment difference (comparator minus zoliflodacin) fell below the 12% non-inferiority margin. The trial is registered with ClinicalTrials.gov, NCT03959527, and EudraCT, 2019-000990-22.

Findings

Between Nov 6, 2019, and March 16, 2023, 1011 patients were screened. 81 patients did not meet screening criteria and 930 participants were randomly assigned to zoliflodacin (n=621) or comparator (n=309). The mean participant age was 29·7 years (SD 9·4). 815 (88%) of 930 participants were assigned male at birth and 115 (12%) participants were assigned female at birth. 514 (55%) of 930 participants were Black or African American, 285 (31%) were Asian, and 113 (12%) were White. Microbiological cure rates at TOC in the microbiological intention-to-treat (urogenital) population (primary efficacy endpoint) were 460 (90·9%, 95% CI 88·1–93·3) of 506 participants for zoliflodacin and 229 (96·2%, 92·9–98·3) of 238 participants for comparator. The estimated difference between groups was 5·3% (95% CI 1·4–8·6) and the upper confidence interval limit was within the prespecified non-inferiority margin of less than 12%. Zoliflodacin was generally well tolerated and adverse events were similar between treatment groups. The most frequently reported treatment-emergent adverse events included headache (61 [10%] of 619 patients), neutropenia (42 [7%]), and leukopenia (24 [4%]) in the zoliflodacin group and injection site pain (38 [12%] of 308 patients), neutropenia (24 [8%]), and diarrhoea (22 [7%]) in the comparator group. The majority of adverse events were mild or moderate in severity. No serious adverse events were reported.

Interpretation

Zoliflodacin was non-inferior to ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhoea and had a similar safety profile. These data suggest a potential role for zoliflodacin as an effective oral treatment option for uncomplicated urogenital gonorrhoea.

DOI: 10.1016/S0140-6736(25)01953-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01953-1/abstract