Redman Rebecca, File Thomas M
Anti-Infectives Clinical Development, Johnson & Johnson Pharmaceutical Research & Development, 6500 Paseo Padre Pkwy., Fremont, CA 94555, USA.
Clin Infect Dis. 2009 Aug 15;49 Suppl 1:S28-35. doi: 10.1086/599813.
Carbapenems remain a mainstay for the empirical treatment of serious nosocomial infection. Although the tolerance and safety profile of the carbapenems as a class is favorable, the primary safety concern is the potential for treatment-emergent seizures. In preclinical testing, doripenem, a new carbapenem antibiotic, showed negligible neurotoxic effects. The safety and tolerability of intravenous doripenem was evaluated in 1 phase 2 and in 6 phase 3 clinical trials conducted with patients with nosocomial pneumonia, including ventilator-associated pneumonia; complicated intra-abdominal infection; and complicated urinary tract infection. Safety data were available from 1817 patients who received doripenem and 1325 patients who received 1 of 4 active comparator drugs as part of this development program. Overall, intravenous doripenem was found to be safe and well tolerated, demonstrating a safety profile comparable to that of comparator agents and a limited propensity to induce seizures, including when administered via 1-h or 4-h infusion. j.
碳青霉烯类药物仍然是严重医院感染经验性治疗的主要药物。尽管作为一类药物，碳青霉烯类药物的耐受性和安全性良好，但主要的安全问题是治疗中出现癫痫发作的可能性。在临床前试验中，新型碳青霉烯类抗生素多利培南显示出可忽略不计的神经毒性作用。在2项2期和6项3期临床试验中，对患有医院获得性肺炎（包括呼吸机相关性肺炎）、复杂性腹腔内感染和复杂性尿路感染的患者，评估了静脉注射多利培南的安全性和耐受性。作为该研发项目的一部分，有1817名接受多利培南治疗的患者和1325名接受4种活性对照药物之一治疗的患者的安全数据。总体而言，发现静脉注射多利培南是安全且耐受性良好的，其安全性与对照药物相当，诱发癫痫发作的倾向有限，包括在通过1小时或4小时输注给药时。j.
