State Key Laboratory of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Beijing Hospital, Beijing, China.
Lancet Infect Dis. 2015 Feb;15(2):161-71. doi: 10.1016/S1473-3099(14)71018-7. Epub 2014 Dec 22.
Ceftriaxone with or without a macrolide antibiotic is a recommended treatment for patients with community-acquired pneumonia requiring hospital admission and intravenous antibiotic treatment. We aimed to assess the efficacy and safety of ceftaroline fosamil compared with ceftriaxone in the treatment of Asian patients admitted to hospital with community-acquired pneumonia.
In this international, randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial, adult Asian patients with Pneumonia Outcomes Research Team (PORT) risk class III-IV acute community-acquired pneumonia were randomly assigned (1:1) to receive intravenous ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (2 g every 24 h) for 5-7 days. Patients were randomly assigned via centralised telephone and web-based system; patients and treating clinicians were masked to treatment allocation. Investigators who did study assessments remained masked to treatment allocation until completion of the study. The primary endpoint was clinical cure at the test-of-cure visit (8-15 days after last dose of study drug) in the clinically evaluable population. Non-inferiority of ceftaroline fosamil was defined as a lower limit of the two-sided 95% CI for the difference in the proportion of patients clinically cured of -10% or higher; if non-inferiority was achieved, superiority was to be concluded if the lower limit of the 95% CI was greater than 0%. This trial is registered with ClinicalTrials.gov, number NCT01371838.
Between Dec 13, 2011, and April 26, 2013, 847 patients were enrolled at 64 centres in China, India, South Korea, Taiwan, and Vietnam, of whom 771 were randomly assigned and 764 received study treatment. In the clinically evaluable population (n=498) 217 (84%) of 258 patients in the ceftaroline fosamil group and 178 (74%) of 240 patients in the ceftriaxone group were clinically cured at the test-of-cure visit (difference 9·9%, 95% CI 2·8-17·1). The superiority of ceftaroline fosamil was consistent across all preplanned patient subgroup analyses (split by age 65 years, age 75 years, sex, PORT risk class, and previous antibiotic use) apart from patients younger than 65 years. The frequency of adverse events was similar between treatment groups and the safety results for ceftaroline fosamil were consistent with the cephalosporin class and previous clinical trial data.
Ceftaroline fosamil 600 mg given every 12 h was superior to ceftriaxone 2 g given every 24 h for the treatment of Asian patients with PORT III-IV community-acquired pneumonia. These data suggest that ceftaroline fosamil should be regarded as an alternative to ceftriaxone in empirical treatment regimens for this patient population.
AstraZeneca.
头孢曲松联合或不联合大环内酯类抗生素是治疗需要住院和静脉用抗生素治疗的社区获得性肺炎患者的推荐治疗方法。我们旨在评估头孢呋辛酯对比头孢曲松治疗亚洲社区获得性肺炎住院患者的疗效和安全性。
在这项国际、随机、对照、双盲、3 期非劣效性嵌套优效性试验中，符合肺炎结局研究小组（PORT）风险类别 III-IV 级急性社区获得性肺炎的成年亚洲患者被随机（1:1）分配接受头孢呋辛酯（每 12 小时 600mg）或头孢曲松（每 24 小时 2g）静脉治疗 5-7 天。患者通过中央电话和基于网络的系统进行随机分组；患者和治疗临床医生对治疗分配情况不知情。进行研究评估的研究者在研究完成前保持对治疗分配情况不知情。主要终点是在治疗结束后（研究药物末次给药后 8-15 天）的治疗中评估人群中的临床治愈率。如果头孢呋辛酯的下限在双侧 95%CI 中低于 -10%或更低，则定义为非劣效性；如果达到非劣效性，则如果 95%CI 的下限大于 0%，则可得出优效性结论。该试验在 ClinicalTrials.gov 注册，编号为 NCT01371838。
2011 年 12 月 13 日至 2013 年 4 月 26 日，在中国、印度、韩国、中国台湾和越南的 64 个中心共招募了 847 名患者，其中 771 名患者被随机分组，764 名患者接受了研究治疗。在临床可评估人群（n=498）中，头孢呋辛酯组 258 例患者中有 217 例（84%）和头孢曲松组 240 例患者中有 178 例（74%）在治疗结束时临床治愈（差异为 9.9%，95%CI 2.8-17.1）。头孢呋辛酯的优效性在所有预先计划的患者亚组分析中是一致的（按年龄 65 岁、75 岁、性别、PORT 风险类别和既往抗生素使用情况进行分层），除了年龄小于 65 岁的患者外。两组的不良事件发生率相似，头孢呋辛酯的安全性结果与头孢菌素类药物和之前的临床试验数据一致。
头孢呋辛酯 600mg 每 12 小时给药优于头孢曲松 2g 每 24 小时给药，用于治疗 PORT III-IV 级社区获得性肺炎的亚洲患者。这些数据表明，头孢呋辛酯应被视为该患者人群经验性治疗方案中头孢曲松的替代药物。
阿斯利康。
