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联合抗生素治疗在儿童炎症性肠病中的疗效。

Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease.

机构信息

Division of Gastroenterology, Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Division of General Pediatrics, Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

出版信息

Inflamm Bowel Dis. 2019 Aug 20;25(9):1586-1593. doi: 10.1093/ibd/izz006.

Abstract

BACKGROUND

Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn's colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center.

METHODS

Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis.

RESULTS

Sixty-three patients with refractory UC, Crohn's colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2-16.5] years; median disease duration [IQR], 1.2 [0.41-4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21-58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti-tumor necrosis factor alpha (anti-TNFα) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40-65) to 10 (0-40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNFα therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08-0.76) and PUCAI ≥65 at baseline (OR, 0.2; 95% CI, 0.05-0.74).

CONCLUSIONS

Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic.

摘要

背景

最近的研究表明,口服联合抗生素可能改善难治性炎症性肠病(IBD)的病程。在这里,我们描述了在一家大型儿科 IBD 中心,将口服联合抗生素作为难治性溃疡性结肠炎(UC)、克罗恩病结肠炎和 IBD 未分类(IBD-U)的挽救治疗。

方法

在这项回顾性队列研究中,对患有医学难治性 IBD 结肠炎的儿童,在抗生素治疗后长达 1 年的时间里,测量临床反应、疾病活动指数、不良事件和临床结局。

结果

63 例难治性 UC、克罗恩病结肠炎和 IBD-U 患者(中位数年龄[四分位距{IQR}],15.3[11.2-16.5]岁;中位数疾病持续时间[IQR],1.2[0.41-4.6]年)接受了 3 或 4 种口服抗生素(最常见的是阿莫西林、甲硝唑,以及多西环素或环丙沙星)联合治疗,中位数(IQR)为 29(21-58)天。34 例患者(54%)被认为是皮质类固醇难治性或依赖型,其中大多数(63/63)以前或现在对抗肿瘤坏死因子-α(抗-TNFα)治疗有反应或原发性无反应。联合使用抗生素可使中位数儿科溃疡性结肠炎活动指数(PUCAI)评分(IQR)从 55(40-65)显著下降至 3±1 周后的 10(0-40)(P<0.0001),63 例患者中有 25 例(39.7%)达到临床缓解(PUCAI<10 分)。口服抗生素的临床益处与抗-TNFα治疗的优化无关。在进入临床缓解的儿童(n=25)中,只有 1 例患者在 1 年随访时需要手术,而在无反应组中,有 10 例患者需要手术。联合使用抗生素的反应的阴性预测因子是使用多西环素(比值比[OR],0.25;95%CI,0.08-0.76)和基线时 PUCAI≥65(OR,0.2;95%CI,0.05-0.74)。

结论

口服联合抗生素似乎是一种有效的挽救和类固醇节约疗法,可在生物治疗失败的短期内诱导缓解。

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