Navalkele Bhagyashri D, Chopra Teena
Internal Medicine and Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA.
Internal Medicine and Infectious Diseases, Infection Prevention and Epidemiology, Detroit Medical Center, Wayne State University, Detroit, MI, USA.
Biologics. 2018 Jan 18;12:11-21. doi: 10.2147/BTT.S127099. eCollection 2018.
infection (CDI) is the most common health care-acquired infection associated with high hospital expenditures. The incidence of subsequent recurrent CDI increases with prior episodes of CDI, 15%-35% risk after primary CDI to 35%-65% risk after the first recurrent episode. Recurrent CDI is one of the most challenging and a very difficult to treat infections. Standard guidelines provide recommendations on treatment of primary CDI. However, treatment choices for recurrent CDI are limited. Recent research studies have focused on the discovery of newer alternatives for prevention of recurrent CDI targeting prime virulence factors involved in pathogenesis. Bezlotoxumab is a human monoclonal antibody directed against toxin B. Multiple in vitro and in vivo animal studies have demonstrated direct binding of bezlotoxumab to toxin B preventing intestinal epithelial damage and colitis. Furthermore, this monoclonal antibody mediates early reconstitution of gut microbiota preventing risk of recurrent CDI. Randomized placebo-controlled trials showed concomitant administration of a single intravenous dose of 10 mg/kg of bezlotoxumab, in patients on standard-of-care therapy for CDI, had no substantial effect on clinical cure rates but significantly reduced the incidence of recurrent CDI (~40%). It shows efficacy against multiple strains, including the epidemic BI/NAP1/027 strain. Bezlotoxumab is a US Food and Drug administration-approved, safe and well-tolerated drug with low risk of serious adverse events and drug-drug interactions. Bezlotoxumab has emerged as a novel dynamic adjunctive therapy for prevention of recurrent CDI. Further studies on real-world experience with bezlotoxumab and its impact in reducing rates of recurrent CDI are needed.
艰难梭菌感染(CDI)是最常见的医疗保健相关感染,与高昂的医院费用相关。随后复发性CDI的发生率会随着CDI先前发作次数的增加而上升,初次CDI后的复发风险为15%-35%,首次复发后的风险为35%-65%。复发性CDI是最具挑战性且极难治疗的感染之一。标准指南提供了关于原发性CDI治疗的建议。然而,复发性CDI的治疗选择有限。近期的研究聚焦于发现针对参与发病机制的主要毒力因子预防复发性CDI的新替代方法。贝佐妥单抗是一种针对毒素B的人单克隆抗体。多项体外和体内动物研究已证明贝佐妥单抗与毒素B直接结合,可预防肠道上皮损伤和结肠炎。此外,这种单克隆抗体介导肠道微生物群的早期重建,预防复发性CDI的风险。随机安慰剂对照试验表明,在接受CDI标准治疗的患者中,同时静脉注射一剂10mg/kg的贝佐妥单抗,对临床治愈率没有实质性影响,但显著降低了复发性CDI的发生率(约40%)。它对多种菌株有效,包括流行的BI/NAP1/027菌株。贝佐妥单抗是一种经美国食品药品监督管理局批准的、安全且耐受性良好的药物,严重不良事件和药物相互作用风险较低。贝佐妥单抗已成为预防复发性CDI的一种新型动态辅助疗法。需要进一步研究贝佐妥单抗在实际应用中的情况及其对降低复发性CDI发生率的影响。