英国伯明翰大学医院NHS基金会的Jonathan D C Ross对庆大霉素与头孢曲松治疗淋病(G-ToG)效果进行了比较，相关论文发表在2019年5月2日出版的《柳叶刀》杂志上。

本研究的目的是评估庆大霉素替代头孢曲松(两者联合阿奇霉素)治疗淋病的有效性。G-ToG是一种在淋病患者身上比较庆大霉素和头孢曲松疗效的多中心、设置平行组的、实用的、随机的、非劣效性试验。患者、治疗医师和评估医师都被是互不见面，只有护士能直接与治疗人员和病人接触。该试验在英国14家性健康诊所进行。确诊患有简单的生殖器、咽部或直肠淋病的年龄在16-70岁的成年人能够参与这项试验。 参与者随机分配肌肉内单次注射庆大霉素240 mg(庆大霉素组)或头孢曲松500 mg(头孢曲松组)，此外，所有参与者还接受了1克口服阿奇霉素。随机化的过程是(1:1)按临床分层，并使用基于web的安全系统进行的。主要结果是清除所有最初感染部位的淋病奈瑟菌，定义为治疗后2周的阴性核酸扩增试验。主要结果分析只包括随访数据的参与者，而不考虑基线访视淋病试验结果。 用于确定非劣效性的差值为风险差的置信下限5%。研究小组没有发现庆大霉素240 mg单次剂量与头孢曲松500 mg单次剂量联合口服阿奇霉素治疗淋病的优势。虽然庆大霉素注射部位的疼痛程度更高，但两组间的副作用相似。庆大霉素不适用于淋病的一线治疗，但对孤立的生殖器感染患者、对头孢曲松过敏或不耐受的患者、或对头孢曲松耐药的患者仍有潜在的治疗作用。进一步的研究需要确定和测试新的替代头孢曲松治疗淋病。

据悉，淋病是一种常见的性传播感染疾病，头孢曲松是目前的一线治疗药，但它的耐药性正在出现。

附：英文原文

Title: Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial  Prof Jonathan D C Ross, MD

Author: Prof Jonathan D C Ross, MD Clare Brittain, BMedSc Michelle Cole, DBMS Claire Dewsnap, MD Jan Harding, PhD Trish Hepburn, BSc Louise Jackson, PhD Matthew Keogh Tessa Lawrence, PhD Prof Alan A Montgomery, PhD Prof Tracy E Roberts, PhD Kirsty Sprange, MSc Wei Tan, MSc Sukhwinder Thandi, PhD John White, FRCP Janet Wilson, FRCP Prof Lelia Duley, MD on behalf of the G-ToG trial team

Issue&Volume: Volume 393,Number 10190,2019

Abstract:

Background Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.

Methods G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.

Findings Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).

Interpretation Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.

DOI: https://doi.org/10.1016/S0140-6736(18)32817-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32817-4/fulltext#