Noel Gary J, Strauss Richard S, Amsler Karen, Heep Markus, Pypstra Rienk, Solomkin Joseph S
Johnson & Johnson Pharmaceutical Research & Development, LLC, 900 Route 202, Raritan, NJ 08869, USA.
Antimicrob Agents Chemother. 2008 Jan;52(1):37-44. doi: 10.1128/AAC.00551-07. Epub 2007 Oct 22.
Ceftobiprole is the first broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) to be assessed in late-stage clinical trials. As a pivotal step in the clinical development of ceftobiprole, a multicenter, global, randomized, double-blind trial was conducted to compare the efficacy of ceftobiprole to that of vancomycin in patients with complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. The primary objective was to assess noninferiority on the basis of the cure rates 7 to 14 days after the completion of therapy in patients administered ceftobiprole 500 mg every 12 h or vancomycin 1 g every 12 h. Of 784 patients randomized, 282 receiving ceftobiprole and 277 receiving vancomycin were clinically evaluable. Of these patients, 93.3% treated with ceftobiprole and 93.5% treated with vancomycin were cured (95% confidence interval of difference, -4.4%, 3.9%). The cure rates for patients with MRSA infections were 91.8% (56/61) with ceftobiprole treatment and 90.0% (54/60) with vancomycin treatment (95% confidence interval of difference, -8.4%, 12.1%). At least one adverse event (AE) was reported by 52% of the ceftobiprole-treated patients and 51% of the vancomycin-treated patients. The most common AEs reported by the ceftobiprole-treated patients were nausea (14%) and taste disturbance (8%). Discontinuation of the study drug because of treatment-emergent AEs occurred in 4% (n = 17) of the ceftobiprole-treated patients and 6% (n = 22) of the vancomycin-treated patients. The results of this trial support the use of ceftobiprole as an effective and well-tolerated treatment option for patients with cSSSIs caused by a spectrum of gram-positive bacteria.
头孢比普是首个在后期临床试验中进行评估的、对耐甲氧西林金黄色葡萄球菌（MRSA）有活性的广谱头孢菌素。作为头孢比普临床开发中的关键一步，开展了一项多中心、全球、随机、双盲试验，以比较头孢比普与万古霉素对革兰氏阳性菌引起的复杂性皮肤及皮肤结构感染（cSSSIs）患者的疗效。主要目的是基于每12小时给予500mg头孢比普或每12小时给予1g万古霉素治疗的患者在治疗完成后7至14天的治愈率来评估非劣效性。在随机分组的784例患者中，282例接受头孢比普治疗和277例接受万古霉素治疗的患者可进行临床评估。在这些患者中，接受头孢比普治疗的患者有93.3%治愈，接受万古霉素治疗的患者有93.5%治愈（差异的95%置信区间为-4.4%，3.9%）。接受头孢比普治疗的MRSA感染患者治愈率为91.8%（56/61），接受万古霉素治疗的为90.0%（54/60）（差异的95%置信区间为-8.4%，12.1%）。52%接受头孢比普治疗的患者和51%接受万古霉素治疗的患者报告了至少一种不良事件（AE）。接受头孢比普治疗的患者报告的最常见AE是恶心（14%）和味觉障碍（8%）。因治疗中出现的AE而停用研究药物的情况在4%（n = 17）接受头孢比普治疗的患者和6%（n = 22）接受万古霉素治疗的患者中发生。该试验结果支持将头孢比普作为由多种革兰氏阳性菌引起的cSSSIs患者的一种有效且耐受性良好的治疗选择。
