Whittall Street Clinic, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK.
Health Technol Assess. 2019 May;23(20):1-104. doi: 10.3310/hta23200.
Gonorrhoea is a common sexually transmitted infection that can cause pain and discomfort, affect fertility in women and lead to epididymo-orchitis in men. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance reducing its effectiveness. Gentamicin is a potential alternative treatment requiring further evaluation.
To assess the clinical effectiveness and cost-effectiveness of gentamicin as an alternative treatment to ceftriaxone in the treatment of gonorrhoea.
A multicentre, parallel-group, blinded, non-inferiority randomised controlled trial.
Fourteen sexual health clinics in England.
Adults aged 16-70 years with a diagnosis of uncomplicated, untreated genital, pharyngeal or rectal gonorrhoea based on a positive Gram-stained smear on microscopy or a positive nucleic acid amplification test (NAAT).
Participants were randomised using a secure web-based system, stratified by clinic. Participants, investigators and research staff assessing participants were blinded to treatment allocation.
Allocation was to either 240 mg of gentamicin (intervention) or 500 mg of ceftriaxone (standard treatment), both administered as a single intramuscular injection. All participants also received 1 g of oral azithromycin.
The primary outcome measure was clearance of at all infected sites, confirmed by a negative Aptima Combo 2® (Hologic Inc., Marlborough, MA, USA) NAAT, at 2 weeks post treatment.
We randomised 720 participants, of whom 81% were men. There were 358 participants in the gentamicin group and 362 in the ceftriaxone group; 292 (82%) and 306 (85%) participants, respectively, were included in the primary analysis. Non-inferiority of gentamicin to ceftriaxone could not be demonstrated [adjusted risk difference for microbiological clearance -6.4%, 95% confidence interval (CI) -10.4% to -2.4%]. Clearance of genital infection was similar in the two groups, at 94% in the gentamicin group and 98% in the ceftriaxone group, but clearance of pharyngeal infection and rectal infection was lower in the gentamicin group (80% vs. 96% and 90% vs. 98%, respectively). Reported pain at the injection site was higher for gentamicin than for ceftriaxone. The side-effect profiles were comparable between the groups. Only one serious adverse event was reported and this was deemed not to be related to the trial medication. The economic analysis found that treatment with gentamicin is not cost neutral compared with standard care, with average patient treatment costs higher for those allocated to gentamicin (£13.90, 95% CI £2.47 to £37.34) than to ceftriaxone (£6.72, 95% CI £1.36 to £17.84).
Loss to follow-up was 17% but was similar in both treatment arms. Twelve per cent of participants had a negative NAAT for gonorrhoea at their baseline visit but this was balanced between treatment groups and unlikely to have biased the trial results.
The trial was unable to demonstrate non-inferiority of gentamicin compared with ceftriaxone in the clearance of gonorrhoea at all infected sites. Clearance at pharyngeal and rectal sites was lower for participants allocated to gentamicin than for those allocated to ceftriaxone, but was similar for genital sites in both groups. Gentamicin was associated with more severe injection site pain. However, both gentamicin and ceftriaxone appeared to be well tolerated.
Exploration of the genetic determinants of antibiotic resistance in will help to identify accurate markers of decreased susceptibility. Greater understanding of the immune response to infection can assist gonococcal vaccine development.
Current Controlled Trials ISRCTN51783227.
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 20. See the NIHR Journals Library website for further project information.
淋病是一种常见的性传播感染，可引起疼痛和不适，影响女性生育能力，并导致男性附睾睾丸炎。目前的治疗方法是使用头孢曲松，但越来越多的证据表明，抗菌药物耐药性降低了其疗效。庆大霉素是一种潜在的替代治疗方法，需要进一步评估。
评估庆大霉素替代头孢曲松治疗淋病的临床疗效和成本效益。
一项多中心、平行组、双盲、非劣效性随机对照试验。
英国 14 家性健康诊所。
年龄在 16-70 岁之间的成年人，根据显微镜下革兰氏染色涂片阳性或核酸扩增试验（NAAT）阳性，诊断为未经治疗的单纯性生殖器、咽或直肠淋病。
参与者使用安全的基于网络的系统进行随机分组，按诊所分层。参与者、研究者和评估参与者的研究人员对治疗分配情况进行了盲法。
所有参与者均接受 240mg 庆大霉素（干预组）或 500mg 头孢曲松（标准治疗组），均为单次肌内注射。所有参与者还接受 1g 口服阿奇霉素。
主要结局指标是所有感染部位的清除率，在治疗后 2 周时通过阴性 Aptima Combo 2®（Hologic Inc.，马萨诸塞州马尔伯勒）NAAT 确认。
我们共随机分配了 720 名参与者，其中 81%为男性。庆大霉素组有 358 名参与者，头孢曲松组有 362 名参与者；分别有 292（82%）和 306（85%）名参与者纳入主要分析。庆大霉素不能证明优于头孢曲松[调整后的微生物学清除率差异-6.4%，95%置信区间（CI）-10.4%至-2.4%]。两组的生殖器感染清除率相似，庆大霉素组为 94%，头孢曲松组为 98%，但咽和直肠感染清除率较低，庆大霉素组分别为 80%和 90%，头孢曲松组分别为 96%和 98%。与头孢曲松相比，注射部位疼痛报告在庆大霉素组中更高。两组的副作用谱相似。仅报告了 1 例严重不良事件，认为与试验药物无关。经济分析发现，与标准护理相比，庆大霉素治疗的成本不具有中性，接受庆大霉素治疗的患者平均治疗费用高于接受头孢曲松治疗的患者（13.90 英镑，95%置信区间 2.47 至 37.34 英镑）（6.72 英镑，95%置信区间 1.36 至 17.84 英镑）。
失访率为 17%，但在两组治疗中相似。12%的参与者在基线时淋病核酸扩增试验（NAAT）结果为阴性，但在两组之间平衡，不太可能影响试验结果。
该试验未能证明庆大霉素与头孢曲松在清除所有感染部位的淋病方面具有非劣效性。与头孢曲松相比，分配给庆大霉素的参与者在咽和直肠部位的清除率较低，但两组在生殖器部位的清除率相似。庆大霉素与更严重的注射部位疼痛有关。然而，庆大霉素和头孢曲松似乎都能很好地耐受。
探索抗生素耐药性的遗传决定因素有助于确定降低敏感性的准确标志物。更好地了解感染的免疫反应有助于淋病疫苗的开发。
当前对照试验 ISRCTN51783227。
本项目由英国国家卫生研究院健康技术评估计划资助，全文将在 ; Vol. 23, No. 20 中发布。有关该项目的更多信息，请访问 NIHR 期刊库网站。
