Cerexa, Inc., Oakland, CA 94612, USA.
J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii53-9. doi: 10.1093/jac/dkr099.
Ceftaroline fosamil, the prodrug of the active metabolite ceftaroline, is a broad-spectrum, parenteral cephalosporin approved for treatment of moderate to severe bacterial infections, including community-acquired pneumonia (CAP). This report provides an integrated safety summary of the ceFtarOline Community-acquired pneUmonia trial versuS ceftriaxone (FOCUS) 1 and 2 trials (registration numbers: NCT00621504 and NCT00509106).
Patients hospitalized with CAP requiring intravenous therapy and having Pneumonia Outcomes Research Team (PORT) risk class scores of III or IV were randomized (1:1) to receive 600 mg of ceftaroline fosamil administered intravenously every 12 h or 1 g of ceftriaxone administered intravenously every 24 h for 5-7 days. All patients were followed for treatment-emergent adverse events (TEAEs) occurring from the start of the initial study drug infusion up to the test-of-cure visit; serious adverse events (SAEs) including deaths occurring up to the late follow-up visit or within 30 days after the last dose were additionally recorded. Scheduled laboratory testing was conducted up to the test-of-cure visit; unscheduled testing continued up to the late follow-up visit.
A total of 1228 patients (613 in the ceftaroline fosamil group and 615 in the ceftriaxone group) received any amount of drug and were included in the safety analysis. The incidences of TEAEs (47.0% versus 45.7%), SAEs (11.3% versus 11.7%), discontinuations (4.4% versus 4.1%) and deaths (2.4% versus 2.0%) were similar between the ceftaroline fosamil and the ceftriaxone groups, respectively. Diarrhoea (4.2%), headache (3.4%) and insomnia (3.1%) were the most commonly reported TEAEs in patients treated with ceftaroline fosamil. The distribution of TEAEs based on severity was also similar between groups, and the majority of patients in both treatment groups (∼75%) had either no TEAEs or only mild TEAEs.
The data from the FOCUS 1 and FOCUS 2 trials presented in this integrated safety summary demonstrate that ceftaroline fosamil is well tolerated, with a tolerability profile similar to ceftriaxone and the cephalosporin class overall, with no unexpected safety concerns being identified.
头孢洛林酯前体药物头孢洛林的活性代谢物，是一种广谱的、注射用头孢菌素，用于治疗包括社区获得性肺炎（CAP）在内的中重度细菌感染。本报告提供了头孢洛林治疗社区获得性肺炎试验与头孢曲松对比（FOCUS）1 和 2 试验（注册号：NCT00621504 和 NCT00509106）的综合安全性总结。
需要静脉治疗且肺炎结局研究小组（PORT）风险评分 III 或 IV 的 CAP 住院患者被随机（1:1）接受每 12 小时静脉注射 600mg 头孢洛林酯或每 24 小时静脉注射 1g 头孢曲松，疗程为 5-7 天。所有患者在初始研究药物输注开始至治愈期访视期间均接受治疗期间出现的不良事件（TEAEs）监测；此外还记录了直至随访结束访视或末次给药后 30 天内的严重不良事件（SAE），包括死亡。直至治愈期访视时进行计划实验室检测；直至随访结束访视时进行非计划检测。
共 1228 例患者（头孢洛林酯组 613 例，头孢曲松组 615 例）接受了任何剂量的药物治疗，并纳入安全性分析。头孢洛林酯组和头孢曲松组的 TEAEs（47.0%与 45.7%）、SAEs（11.3%与 11.7%）、停药（4.4%与 4.1%）和死亡（2.4%与 2.0%）发生率相似。腹泻（4.2%）、头痛（3.4%）和失眠（3.1%）是接受头孢洛林酯治疗的患者中最常见的 TEAEs。两组基于严重程度的 TEAEs 分布也相似，两组大多数患者（~75%）均无 TEAEs 或仅有轻度 TEAEs。
本综合安全性总结中 FOCUS 1 和 FOCUS 2 试验的数据表明，头孢洛林酯耐受性良好，与头孢曲松和整个头孢菌素类药物的耐受性特征相似，未发现新的安全性问题。
