Mikamo Hiroshige, Aoyama Norihiro, Sawata Miyuki, Fujimoto Go, Dorr Mary Beth, Yoshinari Tomoko
Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
Japan Development, MSD K.K., Tokyo, Japan.
J Infect Chemother. 2018 Feb;24(2):123-129. doi: 10.1016/j.jiac.2017.10.005. Epub 2017 Oct 31.
Recurrent Clostridium difficile infection is considered as a significant health care burden. The global study (MODIFY II) of antibody treatment (bezlotoxumab) for the prevention of recurrent C. difficile infection includes Japanese patients (95 subjects); The aim of this subgroup analysis is to report the data obtained from Japanese patients. Patients with C. difficile infection receiving standard of care antibiotic treatment and a single infusion of bezlotoxumab 10 mg/kg, actoxumab 10 mg/kg + bezlotoxumab 10 mg/kg or placebo. Recurrent C. difficile infection through Week 12 was evaluated. In the Full Analysis Set (93 subjects), 91% were older than 65 years of age and 93% were hospitalized at the time of study entry. The standard of care antibiotic for C. difficile infection was metronidazole for 57 subjects and vancomycin for 36 subjects. The recurrent C. difficile infection rate was 46% in the placebo, 21% in the bezlotoxumab (p = 0.0197) and 28% in the actoxumab + bezlotoxumab group. No additive recurrent C. difficile infection-reducing effect with the addition of actoxumab was demonstrated. There were no events representing safety concern in bezlotoxumab. Among 54 clinical isolates of C. difficile as a baseline culture in Japanese patients, the common ribotypes were 052 (28%), 018 (19%), 002 (15%) and 369 (9%). It showed distinctly different distribution from that in the United States and Europe. The superior effect of bezlotoxumab 10 mg/kg in the prevention of recurrent C. difficile infection suggests that the agent will be useful in the rapidly aging Japanese society.
艰难梭菌反复感染被认为是一项重大的医疗负担。一项关于预防艰难梭菌反复感染的抗体治疗（贝佐妥单抗）的全球研究（MODIFY II）纳入了日本患者（95名受试者）；该亚组分析的目的是报告从日本患者中获得的数据。艰难梭菌感染患者接受标准护理抗生素治疗，并单次输注10mg/kg贝佐妥单抗、10mg/kg阿妥莫单抗 + 10mg/kg贝佐妥单抗或安慰剂。对至第12周的艰难梭菌反复感染情况进行了评估。在全分析集（93名受试者）中，91%的患者年龄大于65岁，93%的患者在研究入组时已住院。57名受试者针对艰难梭菌感染的标准护理抗生素为甲硝唑，36名受试者为万古霉素。安慰剂组的艰难梭菌反复感染率为46%，贝佐妥单抗组为21%（p = 0.0197），阿妥莫单抗 + 贝佐妥单抗组为28%。未显示添加阿妥莫单抗具有额外的降低艰难梭菌反复感染的作用。贝佐妥单抗未出现代表安全性问题的事件。在日本患者作为基线培养的54株艰难梭菌临床分离株中，常见的核糖型为052（28%）、018（19%）、002（15%）和369（9%）。其分布与美国和欧洲明显不同。10mg/kg贝佐妥单抗在预防艰难梭菌反复感染方面的卓越效果表明，该药物在快速老龄化的日本社会将有用武之地。
