Advanced Life Sciences, Inc., Woodridge, Illinois, USA.
Antimicrob Agents Chemother. 2012 Apr;56(4):2037-47. doi: 10.1128/AAC.05596-11. Epub 2012 Jan 30.
Community-acquired pneumonia (CAP) continues to be a major health challenge in the United States and globally. Factors such as overprescribing of antibiotics and noncompliance with dosing regimens have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global phase III noninferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild to moderate CAP. Study CL05-001 demonstrated an 83.1% clinical cure rate in the cethromycin group compared with 81.1% in the clarithromycin group (95% confidence interval [CI], -4.8%, +8.9%) in the intent to treat (ITT) population and a 94.0% cethromycin clinical cure rate compared with a 93.8% clarithromycin cure rate (95% CI, -4.5%, +5.1%) in the per protocol clinical (PPc) population. Study CL06-001 achieved an 82.9% cethromycin clinical cure rate in the ITT population compared with an 88.5% clarithromycin cure rate (95% CI, -11.9%, +0.6%), whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group (95% CI, -9.1%, +0.3%). Both studies met the primary endpoints for clinical cure rate based on predefined, sliding-scale noninferiority design. Therefore, in comparison with clarithromycin, these two noninferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects with Streptococcus pneumoniae bacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.
社区获得性肺炎（CAP）仍然是美国和全球的主要健康挑战。抗生素过度处方和不遵守剂量方案等因素加剧了日益严重的抗菌药物耐药问题。此外，几种可用于治疗 CAP 的药物已被发现与严重的副作用有关。塞妥霉素是一种新的酮内酯类抗生素，可能为处方医生提供一种额外的治疗药物，以补充不断减少的治疗手段。两项全球 III 期非劣效性研究（CL05-001 和 CL06-001）旨在评估塞妥霉素的安全性和疗效，研究对象为患有轻度至中度 CAP 的患者。CL05-001 研究结果显示，意向治疗（ITT）人群中，塞妥霉素组的临床治愈率为 83.1%，而克拉霉素组为 81.1%（95%置信区间[CI]：-4.8%，+8.9%）；在符合方案（PPc）人群中，塞妥霉素组的临床治愈率为 94.0%，而克拉霉素组为 93.8%（95%CI：-4.5%，+5.1%）。CL06-001 研究结果显示，ITT 人群中，塞妥霉素组的临床治愈率为 82.9%，而克拉霉素组为 88.5%（95%CI：-11.9%，+0.6%）；PPc 人群中，塞妥霉素组的临床治愈率为 91.5%，而克拉霉素组为 95.9%（95%CI：-9.1%，+0.3%）。这两项研究均达到了基于预设滑动比例非劣效性设计的主要临床治愈率终点。因此，与克拉霉素相比，这两项非劣效性研究表明塞妥霉素具有疗效和安全性，并且在肺炎链球菌菌血症患者中具有令人鼓舞的疗效。研究期间未观察到临床意义上的不良事件。塞妥霉素可能成为门诊治疗 CAP 的一种有潜力的口服治疗药物。
