Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure, infections
Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure, infections
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DOI：
10.1128/aac.00590-07
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发表时间：
2007-10-01
影响因子：
4.9
通讯作者：
Ge, Yigong
中科院分区：
文献类型：
--
作者：
Talbot, George H.;Thye, Dirk;Ge, Yigong
头孢洛林是头孢洛林酯（以前称为PPI-0903、TAK-599）的生物活性代谢产物，是一种广谱头孢菌素，对多重耐药革兰氏阳性需氧病原体（包括耐甲氧西林金黄色葡萄球菌）具有强效体外活性。进行了一项随机、双盲研究，以评价头孢洛林与标准疗法相比治疗复杂性皮肤和皮肤结构感染（cSSSI）的安全性和有效性。将患有cSSSI（包括至少一种全身性炎症标志物）的成人随机（2：1）接受静脉内（i. v.）头孢洛林（600 mg，每12 h）或静脉注射万古霉素（1 g，每12 h），伴或不伴静脉注射氨曲南（1 g，每8 h），持续7至14天。主要结局指标是治疗后8至14天治愈检验（TOC）访视时的临床治愈率。次要结局包括TOC时的微生物成功率（根除或假定根除）和治疗后21 - 28天的临床复发率。在入组的100例受试者中，88例可进行临床评价;头孢洛林的临床治愈率为96.7%（59/61），标准治疗为88.9%（24/27）。在微生物学可评价的受试者中（即，临床可评估，并且在基线时分离出至少一种敏感病原体），头孢洛林的微生物学成功率为95.2%（40/42），而标准治疗为85.7%（18/21）。每组各有1例受试者发生复发（头孢洛林，1.8%;标准治疗，4.3%）。头孢洛林表现出非常有利的安全性和耐受性特征，与市售头孢菌素一致。头孢洛林的大多数不良事件是轻度的，与治疗无关。头孢洛林有望成为治疗cSSSI和其他严重多微生物感染的新疗法。
Ceftaroline, the bioactive metabolite of ceftaroline fosamil (previously PPI-0903, TAK-599), is a broadspectrum cephalosporin with potent in vitro activity against multidrug-resistant gram-positive aerobic pathogens, including methicillin-resistant Staphylococcus aureus. A randomized, observer-blinded study to evaluate the safety and efficacy of ceftaroline versus standard therapy in treating complicated skin and skin structure infections (cSSSI) was performed. Adults with cSSSI, including at least one systemic marker of inflammation, were randomized (2:1) to receive intravenous (i.v.) ceftaroline (600 mg every 12 h) or i.v. vancomycin (I g every 12 h) with or without adjunctive i.v. aztreonam (1 g every 8 h) for 7 to 14 days. The primary outcome measure was the clinical cure rate at a test-of-cure (TOC) visit 8 to 14 days after treatment. Secondary outcomes included the microbiological success rate (eradication or presumed eradication) at TOC and the clinical relapse rate 21 to 28 days following treatment. Of 100 subjects enrolled, 88 were clinically evaluable; the clinical cure rate was 96.7% (59/61) for ceftaroline versus 88.9% (24/27) for standard therapy. Among the microbiologically evaluable subjects (i.e., clinically evaluable and having had at least one susceptible pathogen isolated at baseline), the microbiological success rate was 95.2% (40/42) for ceftaroline versus 85.7% (18/21) for standard therapy. Relapse occurred in one subject in each group (ceftaroline, 1.8%; standard therapy, 4.3%). Ceftaroline exhibited a very favorable safety and tolerability profile, consistent with that of marketed cephalosporins. Most adverse events from ceftaroline were mild and not related to treatment. Ceftaroline holds promise as a new therapy for treatment of cSSSI and other serious polymicrobial infections.