Albany College of Pharmacy and Health Sciences, Albany, New York, NY 12208, USA.
Drugs. 2012 Jul 30;72(11):1473-93. doi: 10.2165/11635660-000000000-00000.
Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum β-lactamases, class B metallo-β-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation of lesion spread and absence of fever, was 74.0% in the ceftaroline fosamil group compared with 66.2% in the vancomycin plus aztreonam group (treatment difference 7.8%, 95% CI 1.3, 14.0). Clinical efficacy of ceftaroline fosamil in 1240 hospitalized adults with CAP was compared with that of ceftriaxone in two additional phase III trials (FOCUS 1 and FOCUS 2). Of note, because ceftriaxone does not have activity against MRSA, patients with confirmed or suspected MRSA CAP were excluded from the FOCUS trials. Results demonstrated that ceftaroline was noninferior to ceftriaxone, with 84.3% in the ceftaroline fosamil group achieving clinical cure compared with 77.7% in the ceftriaxone group (difference 6.7%, 95% CI 1.6, 11.8). An additional analysis of the trials was conducted in patients with moderate to severe CAP and at least one proven typical bacterial pathogen at baseline (i.e. CABP). Day 4 clinical response rates were 69.5% for ceftaroline and 59.4% for ceftriaxone (difference 10.1%, 95% CI -0.6, 20.6). In the phase III trials, adverse event rates were similar between groups. Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP.
头孢呋辛酯是一种头孢菌素类抗菌药物，已获得美国食品和药物管理局（FDA）批准，用于治疗急性细菌性皮肤和皮肤结构感染（ABSSSI）和社区获得性细菌性肺炎（CABP）。静脉给药后，头孢呋辛酯迅速转化为其生物活性代谢物头孢呋辛。头孢呋辛对革兰阳性菌和革兰阴性菌具有广谱体外活性，包括当代耐药的革兰阳性表型，如耐甲氧西林金黄色葡萄球菌（MRSA）和多药耐药肺炎链球菌。由于其独特的活性谱，临床和实验室标准研究所（CLSI）将头孢呋辛指定为新型β-内酰胺类抗菌药物的成员，具有抗 MRSA 活性的头孢菌素类药物。头孢呋辛对金黄色葡萄球菌的活性扩展至异质性耐万古霉素中间型、万古霉素中间型、万古霉素耐药和达托霉素不敏感分离株。头孢呋辛对所有测试链球菌的最低抑菌浓度（MIC）都很低，对青霉素耐药程度不同的肺炎链球菌分离株具有强大的活性。头孢呋辛对粪肠球菌和屎肠球菌以及脆弱拟杆菌等厌氧菌的活性有限。头孢呋辛的体外活性包括许多革兰阴性病原体，但不包括产生超广谱β-内酰胺酶、B 型金属β-内酰胺酶或 AmpC 头孢菌素酶的细菌，也不包括大多数非发酵革兰阴性杆菌。头孢呋辛酯已在 III 期随机、双盲、国际、多中心非劣效性临床试验中研究用于治疗复杂性皮肤和皮肤结构感染（cSSSI）和社区获得性肺炎（CAP）。两项相同的试验（CANVAS 1 和 CANVAS 2）比较了头孢呋辛酯与万古霉素加氨曲南在 1378 例 cSSSI 成人中的疗效。结果表明，头孢呋辛酯与万古霉素加氨曲南相比不劣效，头孢呋辛酯组 91.6%（汇总分析）达到临床反应，而万古霉素加氨曲南组为 92.7%（差异-1.1%，95%CI-4.2,2.0）。一项额外的分析评估了在治疗第 3 天符合 FDA 指导定义的 ABSSSI 的患者亚组中的临床治愈率。临床反应定义为病变扩散停止和无发热，头孢呋辛酯组为 74.0%，而万古霉素加氨曲南组为 66.2%（治疗差异 7.8%，95%CI 1.3,14.0）。在另外两项 III 期试验（FOCUS 1 和 FOCUS 2）中，比较了头孢呋辛酯在 1240 例住院 CAP 成人中的疗效。值得注意的是，由于头孢曲松对 MRSA 没有活性，因此排除了患有确诊或疑似 MRSA CAP 的患者参加 FOCUS 试验。结果表明，头孢呋辛酯与头孢曲松相比不劣效，头孢呋辛酯组 84.3%达到临床治愈率，而头孢曲松组为 77.7%（差异 6.7%，95%CI 1.6,11.8）。对试验进行了一项额外分析，纳入了中度至重度 CAP 患者和基线时至少有一种已证实的典型细菌病原体（即 CABP）。第 4 天的临床反应率分别为头孢呋辛组 69.5%和头孢曲松组 59.4%（差异 10.1%，95%CI-0.6,20.6）。在 III 期试验中，两组的不良反应发生率相似。总体而言，头孢呋辛酯耐受性良好，这与头孢菌素类药物良好的安全性和耐受性一致。综上所述，头孢呋辛酯是一种广谱的头孢菌素类药物，对耐药的革兰阳性病原体具有极好的体外活性，包括耐甲氧西林金黄色葡萄球菌（MRSA）以及许多常见的革兰阴性菌。它是 ABSSSI 和 CABP 的一种受欢迎的治疗选择。
