Integrated Analysis of FOCUS 1 and FOCUS 2: Randomized, Doubled-Blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline Fosamil versus Ceftriaxone in Patients with Community-Acquired Pneumonia
Integrated Analysis of FOCUS 1 and FOCUS 2: Randomized, Doubled-Blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline Fosamil versus Ceftriaxone in Patients with Community-Acquired Pneumonia
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DOI：
10.1086/657313
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发表时间：
2010-12-15
影响因子：
11.8
通讯作者：
Thye, Dirk
中科院分区：
文献类型：
--
作者：
File, Thomas M., Jr.;Low, Donald E.;Thye, Dirk
背景头孢洛林是头孢洛林酯的活性形式，是一种广谱头孢菌素，对引起社区获得性肺炎（CAP）的病原体（包括肺炎链球菌）具有杀菌活性。在两项随机、双盲、多中心试验中评价了头孢洛林治疗CAP的效果：头孢洛林社区获得性肺炎试验与头孢曲松治疗住院患者试验（FOCUS）1和FOCUS 2。需要静脉治疗的肺炎结局研究小组风险等级III或IV CAP住院患者（但未入住重症监护室）随机接受头孢洛林600 mg每12 h一次或头孢曲松1 g每24 h一次，持续5-7天。FOCUS 1组患者在第1天口服克拉霉素500 mg，每12 h 1次，共2次。在个体试验中，头孢洛林与头孢曲松临床可评价（CE）人群的临床治愈率如下：FOCUS 1，86.6% vs 78.2%（差异，8.4%; 95%置信区间[CI]，1.4%-15.4%）; FOCUS 2，82.1% vs 77.2%（差异，4.9%; 95%CI，-2.5%至12.5%）。在综合分析中，614例患者接受头孢洛林，614例接受头孢曲松。在接受头孢洛林治疗的CE患者中，84.3%达到临床治愈，而头孢曲松治疗的患者为77.7%（差异为6.7%; 95% CI，1.6%-11.8%）。改良意向治疗疗效人群的临床治愈率为82.6%，头孢洛林和头孢曲松为76.6%（差异为6.0%; 95% CI，1.4%-10.7%）。头孢洛林和头孢曲松耐受性良好;两个治疗组的不良事件、严重不良事件、死亡和因不良事件导致的提前停药率相似。在个体试验中，头孢洛林非劣效于头孢曲松。在该综合分析中，头孢洛林组的临床治愈率在数值上高于头孢曲松组。头孢洛林耐受性良好，安全性与头孢曲松相似。
Background. Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against pathogens causing community-acquired pneumonia (CAP), including Streptococcus pneumoniae. Ceftaroline was evaluated for the treatment of CAP in 2 randomized, double-blind, multicenter trials: Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients (FOCUS) 1 and FOCUS 2.Methods. Patients hospitalized (but not admitted to an intensive care unit) with Pneumonia Outcomes Research Team risk class III or IV CAP requiring intravenous therapy were randomized to ceftaroline 600 mg every 12 h or ceftriaxone 1 g every 24 h for 5-7 days. Patients in FOCUS 1 received 2 doses of oral clarithromycin 500 mg every 12 h on day 1.Results. In the individual trials, clinical cure rates in the clinically evaluable (CE) population for ceftaroline versus ceftriaxone were as follows: FOCUS 1, 86.6% vs 78.2% (difference, 8.4%; 95% confidence interval [CI], 1.4%-15.4%); FOCUS 2, 82.1% vs 77.2% (difference, 4.9%; 95% CI, -2.5% to 12.5%). In the integrated analysis, 614 patients received ceftaroline and 614 received ceftriaxone. Of the CE patients treated with ceftaroline, 84.3% achieved clinical cure, compared with 77.7% of ceftriaxone-treated patients (difference, 6.7%; 95% CI, 1.6%-11.8%). Clinical cure rates in the modified intent-to-treat efficacy population were 82.6% versus 76.6% for ceftaroline and ceftriaxone (difference, 6.0%; 95% CI, 1.4%-10.7%). Ceftaroline and ceftriaxone were well tolerated; rates of adverse events, serious adverse events, deaths, and premature discontinuations caused by an adverse event were similar in both treatment arms.Conclusions. Ceftaroline was noninferior to ceftriaxone in the individual trials. In this integrated analysis, clinical cure rates for the ceftaroline group were numerically higher than those for the ceftriaxone group. Ceftaroline was well tolerated, with a safety profile similar to that of ceftriaxone.