Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)
Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)
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DOI：
10.1016/j.vaccine.2009.10.144
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发表时间：
2010-01-22
期刊：
影响因子：
5.5
通讯作者：
Molrine, Deborah
中科院分区：
文献类型：
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作者：
Leav, Brett A.;Blair, Barbra;Molrine, Deborah
背景。先前的研究已证明艰难梭菌抗毒素 A 血清抗体与预防症状性疾病和复发的方法之间存在相关性。 MBL 和 Medarex, Inc 开发的抗艰难梭菌毒素 A (CDA1) 的中和单克隆抗体在接受艰难梭菌感染 (CDI) 标准护理治疗的患者中进行了一项 II 期随机、双盲、安慰剂对照试验。29 名受试者接受单次静脉输注 10 mg/kg CDA1，17 名受试者接受安慰剂，并在 56 天的研究期间评估 CDI 复发情况在输注前后的不同时间点通过 ELISA 和细胞毒性测定法测量抗艰难梭菌毒素 A 和 B 的抗体。结果。 CDA1 组 29 例中有 5 例 (17%) 发生 CDI 复发，安慰剂组 17 例中有 3 例 (18%) (p = NS)，并且 CDA1 治疗组的复发时间有延迟的趋势 毒素 B 受体结合结构域表位抗体的几何平均浓度（分别为 0 300 和 1 20 μ g/ml。p = 0 02）和中和效价的几何平均滴度研究第 28 天时，复发受试者的 B 抗体（分别为 8·00 和 100。p = 0·02）低于未复发受试者。此外，与未复发受试者相比，复发受试者感染流行性 BI/NAP1/027 毒株的比例显着更高（88% 对比 22%，p = 0·002）。最后。在第 14 天中和抗毒素 B 的多重逻辑回归分析中 (p < 0.001)。第 28 天的抗毒素 A (p < 0.001) 和入组时 BI/NAP1/027 菌株的感染 (p = 0.002) 都是 CDI 复发的预测因素。在这项前瞻性研究中，较低浓度的中和抗毒素 B 和抗毒素 A 抗体以及艰难梭菌 BI/NAP1/027 菌株感染与 CDI 复发显着相关（D 2009 Elsevier Ltd 版权所有
Background. Previous Studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrenceMethods. A neutralizing monoclonal antibody to C difficile toxin A (CDA1)developed by MBL and Medarex, Inc was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C difficile infection (CDI) Twenty-nine subjects received a single intravenous infusion of 10 mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period Serum antibodies against C difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion.Findings. CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p = NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1 The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0 300 and 1 20 mu g/ml, respectively. p = 0 02) and geometric mean titer of neutralizing B antibody (8 00 and 100, respectively. p = 0 02) at Study day 28 were lower for those Subjects with recurrence compared to those who did not recur In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%, p = 0 002). Finally. in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p < 0 001). anti-toxin A at day 28 (p < 0.001) and infection with the BI/NAP1/027 strain at enrollment (p = 0 002) were all predictive of CDI recurrenceInterpretation. In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C difficile were significantly associated with recurrence of CDI (D 2009 Elsevier Ltd All rights reserved