Mount Sinai Hospital/University Health Network, Toronto, Ontario, Canada.
J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii33-44. doi: 10.1093/jac/dkr097.
Ceftaroline (active form of the prodrug ceftaroline fosamil) is a novel cephalosporin with activity against pathogens commonly associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Gram-negative pathogens. This randomized, double-blind, Phase III study evaluated the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ -10%] of clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations.
Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 2 registration number NCT00509106 (http://clinicaltrials.gov/ct2/show/NCT00509106).
The study enrolled 627 patients, 315 of whom received ceftaroline fosamil and 307 of whom received ceftriaxone. Patients in both treatment groups had comparable baseline characteristics. Clinical cure rates were as follows: CE population, 82.1% (193/235) for ceftaroline fosamil and 77.2% (166/215) for ceftriaxone [difference (95% CI), 4.9% (-2.5, 12.5)]; and MITTE population, 81.3% (235/289) for ceftaroline fosamil and 75.5% (206/273) for ceftriaxone [difference (95% CI), 5.9% (-1.0, 12.7)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE (mMITTE) population were 83.3% (35/42) and 70.0% (28/40) for ceftaroline fosamil and ceftriaxone, respectively. Ceftaroline fosamil and ceftriaxone were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations due to an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, hypokalaemia, insomnia and phlebitis, and the most common AEs for ceftriaxone-treated patients were diarrhoea, insomnia, phlebitis and hypertension.
Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP.
头孢洛林（前体药物头孢洛林磷酸酯的活性形式）是一种新型头孢菌素，对社区获得性肺炎（CAP）常见的病原体具有活性，包括肺炎链球菌和革兰氏阴性病原体。这项随机、双盲、III 期研究评估了头孢洛林磷酸酯治疗 CAP 患者的疗效和安全性。主要目的是确定头孢洛林磷酸酯在临床可评估（CE）和改良意向治疗疗效（MITTE）人群中的临床治愈率与头孢曲松相比的非劣效性[下限 95%置信区间（CI）≥-10%]。
患有肺炎结局研究小组（PORT）风险类别 III 或 IV 的 CAP 的患者在非重症监护病房住院，需要静脉（iv）治疗，他们被随机（1:1）接受 600mg 头孢洛林磷酸酯 iv 每 12 小时或 1g 头孢曲松 iv 每 24 小时。评估临床治愈率、微生物学反应、不良事件（AE）和实验室检查。FOCUS 2 注册号 NCT00509106（http://clinicaltrials.gov/ct2/show/NCT00509106）。
该研究纳入了 627 名患者，其中 315 名接受了头孢洛林磷酸酯治疗，307 名接受了头孢曲松治疗。两组患者的基线特征具有可比性。临床治愈率如下：CE 人群中，头孢洛林磷酸酯为 82.1%（193/235），头孢曲松为 77.2%（166/215）[差异（95%CI），4.9%（-2.5，12.5）]；MITTE 人群中，头孢洛林磷酸酯为 81.3%（235/289），头孢曲松为 75.5%（206/273）[差异（95%CI），5.9%（-1.0，12.7）]。在微生物学 MITTE（mMITTE）人群中，由肺炎链球菌引起的 CAP 的临床治愈率分别为头孢洛林磷酸酯 83.3%（35/42）和头孢曲松 70.0%（28/40）。头孢洛林磷酸酯和头孢曲松均具有良好的耐受性，AE、严重 AE、死亡和因 AE 而停药的发生率相似。头孢洛林磷酸酯治疗患者中最常见的 AE 为腹泻、头痛、低钾血症、失眠和静脉炎，头孢曲松治疗患者中最常见的 AE 为腹泻、失眠、静脉炎和高血压。
头孢洛林磷酸酯在 PORT 风险类别 III 或 IV 的 CAP 住院患者中实现了较高的临床治愈率和微生物学反应率。头孢洛林磷酸酯具有良好的耐受性，安全性与头孢曲松和其他头孢菌素相似。头孢洛林磷酸酯是治疗 CAP 的一种有前途的药物。
