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头孢洛林酯氨丁三醇作为一种潜在的治疗成人社区获得性肺炎金黄色葡萄球菌的治疗选择。

Ceftaroline fosamil as a potential treatment option for Staphylococcus aureus community-acquired pneumonia in adults.

机构信息

University of Hannover, School of Medicine, Carl-Neuberg-Straße, 30625 Hannover, Germany.

Pfizer, 23-25 Avenue du Dr Lannelongue, 75668 Paris, France.

出版信息

Int J Antimicrob Agents. 2019 Oct;54(4):410-422. doi: 10.1016/j.ijantimicag.2019.08.012. Epub 2019 Aug 9.

Abstract

Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), is an important aetiological cause of community-acquired pneumonia (CAP) and associated with significant morbidity and mortality. Empiric therapy for CAP frequently consists of β-lactam monotherapy or β-lactam/macrolide combination therapy. However, such agents are often ineffective against S. aureus and do not reflect the emergence and increasing prevalence of MRSA in the community setting. Ceftaroline fosamil is a fifth-generation parenteral cephalosporin with broad-spectrum activity against Gram-positive pathogens - such as S. aureus (including MRSA), Streptococcus pneumoniae and Streptococcus pyogenes - and typical Gram-negative pathogens, including Haemophilus influenzae and Moraxella catarrhalis. The approval of ceftaroline fosamil in the United States and Europe for the treatment of adults with moderate-to-severe CAP was based on two phase 3 trials (FOCUS 1 and 2), which demonstrated that ceftaroline fosamil was non-inferior to ceftriaxone, a standard empiric treatment for CAP, while exhibiting a comparable safety profile. Although head-to-head trials of ceftaroline fosamil versus comparators against MRSA CAP are lacking, the effectiveness of ceftaroline fosamil in subpopulations of patients not covered by phase 3 trials (e.g. those with MRSA CAP or severe renal impairment) has been demonstrated in the Clinical Assessment Program and Teflaro Utilization Registry (CAPTURE) study. As ineffective empiric therapy is associated with adverse outcomes, including mortality and increased costs, ceftaroline fosamil, with its extended spectrum of activity, is an attractive alternative to standard antibiotic CAP regimens.

摘要

金黄色葡萄球菌(S. aureus),包括耐甲氧西林金黄色葡萄球菌(MRSA),是社区获得性肺炎(CAP)的重要病因,与较高的发病率和死亡率相关。CAP 的经验性治疗通常包括β-内酰胺单药治疗或β-内酰胺/大环内酯类联合治疗。然而,这些药物通常对金黄色葡萄球菌无效,也不能反映社区环境中 MRSA 的出现和日益流行。头孢洛林酯是一种具有广谱抗革兰阳性病原体活性的第五代注射用头孢菌素,包括金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌)、肺炎链球菌和化脓性链球菌,以及典型的革兰氏阴性病原体,包括流感嗜血杆菌和卡他莫拉菌。头孢洛林酯在美国和欧洲获得批准,用于治疗中重度 CAP 成人患者,这是基于两项 3 期临床试验(FOCUS1 和 2),这些试验表明,头孢洛林酯与 CAP 的标准经验性治疗药物头孢曲松相比具有非劣效性,同时具有相似的安全性。虽然缺乏头孢洛林酯与抗 MRSA CAP 的对照药物的头对头试验,但头孢洛林酯在 3 期临床试验未涵盖的患者亚组(如耐甲氧西林金黄色葡萄球菌 CAP 或严重肾功能损害)中的有效性已在临床评估计划和 Teflaro 利用登记处(CAPTURE)研究中得到证实。由于无效的经验性治疗与不良后果相关,包括死亡率和增加的成本,具有广谱活性的头孢洛林酯是标准抗生素 CAP 方案的一个有吸引力的替代方案。

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