Campbell University College of Pharmacy and Health Sciences, 5505 Spence Plantation Lane, Holly Springs, NC 27540, USA.
Expert Rev Anti Infect Ther. 2011 Aug;9(8):567-72. doi: 10.1586/eri.11.82.
Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP. Ceftaroline fosamil, the prodrug of ceftaroline, is a new extended-spectrum cephalosporin that exhibits time-dependant bactericidal activity against numerous Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. pneumoniae. Notable exceptions include Pseudomonas spp. and Gram-negative organisms that produce extended-spectrum β-lactamases or carbapenemases. Two large Phase III clinical trials (FOCUS 1 and 2) reported that ceftaroline fosamil was well tolerated, with a clinical cure rate of CAP that was noninferior to that with ceftriaxone in nonintensive care unit adult inpatients with moderately severe (Pneumonia Outcomes Research Team score of III or IV) community-acquired pneumonia.
在过去的几十年中,由于头孢菌素具有广泛的微生物学活性和良好的安全性,因此被广泛用于治疗多种感染(通常作为一线抗生素治疗)。目前,美国传染病学会的指南将第三代头孢菌素与大环内酯类抗生素联合作为治疗重症监护室外成人社区获得性肺炎(CAP)的选择之一。虽然头孢曲松常用于 CAP 的治疗,但耐多药肺炎链球菌的发病率不断上升,以及对无效治疗相关不良后果的担忧,促使人们寻找一种耐受性良好且对可引起 CAP 的细菌有效的治疗替代药物。头孢洛林酯是头孢洛林的前体药物,是一种新型的扩展谱头孢菌素,对许多革兰氏阴性和革兰氏阳性菌具有时间依赖性杀菌活性,包括耐甲氧西林金黄色葡萄球菌和耐青霉素肺炎链球菌。值得注意的例外包括铜绿假单胞菌和产生超广谱β-内酰胺酶或碳青霉烯酶的革兰氏阴性菌。两项大型 III 期临床试验(FOCUS1 和 2)报告称,头孢洛林酯耐受性良好,其 CAP 的临床治愈率与非重症监护病房成人中度严重(肺炎结局研究组评分 III 或 IV)社区获得性肺炎患者的头孢曲松非劣效。