Rupp Mark E, Holley H Preston, Lutz Jon, Dicpinigaitis Peter V, Woods Christopher W, Levine Donald P, Veney Naomi, Fowler Vance G
Division of Infectious Diseases, University of Nebraska Medical Center, 984031 Nebraska Medical Center, Omaha, NE 68198-4031, USA.
Antimicrob Agents Chemother. 2007 Dec;51(12):4249-54. doi: 10.1128/AAC.00570-07. Epub 2007 Sep 24.
New treatment modalities are needed for the treatment of infections due to multidrug-resistant Staphylococcus aureus. S. aureus capsular polysaccharide immune globulin (Altastaph) is a polyclonal immune globulin preparation that is being developed as adjunctive therapy for persons with S. aureus infections complicated by bacteremia. In a phase II, multicenter, randomized, double-blind, placebo-controlled trial, 40 subjects with documented S. aureus bacteremia received standard therapy plus either Altastaph at 200 mg/kg of body weight in each of two infusions 24 h apart or placebo. During the 42-day observation period, antibody pharmacokinetics and safety were the primary characteristics studied. Information regarding the resolution of bacteremia and fever was also analyzed. Anti-type-5 and anti-type-8 capsular antibody levels peaked after the second infusion at 550 mug/ml and 419 mug/ml, respectively, and remained above 100 mug/ml at day 28. A total of 316 adverse events were noted in 39 of 40 subjects. Infusion-related adverse events in Altastaph recipients were infrequent and similar to those among recipients of commercial intravenously administered immunoglobulin G products. Five of 21 (23%) subjects in the Altastaph group died, whereas 2 of 18 (11%) subjects in the placebo group died (P = 0.42). Compared to the control patients, the Altastaph recipients had a shorter median time to the resolution of fever (2 days and 7 days, respectively; P = 0.09) and a shorter length of hospital stay (9 days and 14 days, respectively; P = 0.03). However, these findings are exploratory, and there were few differences in the other variables measured. High levels of opsonizing antibodies were maintained for the initial 4 weeks. Although the study was not powered to show efficacy, these preliminary findings and safety profile suggest that Altastaph may be an effective adjunct to antibiotics and warrants further investigation (ClinicalTrials.gov number NCT00063089).
治疗耐多药金黄色葡萄球菌感染需要新的治疗方法。金黄色葡萄球菌荚膜多糖免疫球蛋白（Altastaph）是一种多克隆免疫球蛋白制剂，正被开发用作金黄色葡萄球菌感染并发菌血症患者的辅助治疗。在一项II期、多中心、随机、双盲、安慰剂对照试验中，40例有记录的金黄色葡萄球菌菌血症患者接受标准治疗，外加每24小时输注一次、每次剂量为200mg/kg体重的Altastaph或安慰剂。在42天的观察期内，抗体药代动力学和安全性是主要研究特征。还分析了有关菌血症和发热消退的信息。抗5型和抗8型荚膜抗体水平在第二次输注后分别达到峰值，为550μg/ml和419μg/ml，并在第28天保持在100μg/ml以上。40例受试者中有39例共记录到316起不良事件。接受Altastaph的受试者中与输注相关的不良事件很少，与接受市售静脉注射免疫球蛋白G产品的受试者相似。Altastaph组21例受试者中有5例（23%）死亡，而安慰剂组18例受试者中有2例（11%）死亡（P = 0.42）。与对照患者相比，接受Altastaph的受试者发热消退的中位时间较短（分别为2天和7天；P = 0.09），住院时间较短（分别为9天和14天；P = 0.03）。然而，这些发现具有探索性，在其他测量变量方面差异不大。在最初4周内维持了高水平的调理抗体。尽管该研究没有足够的能力显示疗效，但这些初步发现和安全性表明，Altastaph可能是抗生素的有效辅助药物，值得进一步研究（ClinicalTrials.gov编号NCT00063089）。
