Fischer Monika, Kao Dina, Mehta Shama R, Martin Tracey, Dimitry Joseph, Keshteli Ammar H, Cook Gwendolyn K, Phelps Emmalee, Sipe Brian W, Xu Huiping, Kelly Colleen R
Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA.
Department of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, Edmonton, Alberta, Canada.
Am J Gastroenterol. 2016 Jul;111(7):1024-31. doi: 10.1038/ajg.2016.180. Epub 2016 May 17.
Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.
Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.
Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.
Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.
粪便微生物群移植（FMT）是治疗复发性或难治性艰难梭菌感染（CDI）的一种高效疗法；然而，10% - 20%的患者在接受单次FMT后未能治愈。本研究的目的是确定与FMT失败相关的风险因素，并开发和验证FMT失败的预测模型。
前瞻性收集了2011年至2015年在三个学术性三级转诊中心接受治疗的患者的特征、CDI病史、FMT特征和结局数据。早期FMT失败定义为在FMT后1个月内出现与粪便艰难梭菌毒素或PCR阳性相关的腹泻无反应或复发。晚期FMT失败定义为在FMT后1至3个月内出现与粪便艰难梭菌毒素或PCR阳性相关的腹泻复发。来自两个中心的患者数据用于确定FMT失败的独立预测因素并建立预测模型。基于最终预测因素的系数构建风险指数。来自第三个中心的患者队列用于验证预测模型。
在发育队列的328例患者中，73.5%（N = 241）为女性，平均年龄61.4±19.3岁；19.2%（N = 63）患有炎症性肠病（IBD），23.5%（N = 77）免疫功能低下。FMT的指征为复发性CDI的占87.2%（N = 286），严重或严重复杂型的占12.8%（N = 42）。16.7%（N = 54）的FMT是在住院期间进行的。40%（N = 130）的病例粪便来源是患者指定的捐赠者。早期FMT失败率为18.6%，晚期失败率为2.7%。在多变量分析中，早期FMT失败的预测因素包括严重或严重复杂型CDI（比值比（OR）5.95，95%置信区间（CI）：2.26 - 15.62）、FMT期间的住院状态（OR 3.78，95%CI：1.55 - 9.24）以及先前与CDI相关的住院治疗（OR 1.43，95%CI：1.18 - 1.75）；每增加一次住院，失败几率增加43%。风险评分范围为0至13，0表示低风险，1 - 2表示中度风险，≥3表示高风险。在发育队列中，低风险患者的早期FMT失败率为5.6%，中度风险患者为12.7%，高风险患者为41%。在验证队列的134例患者中，57%（N = 77）为女性，平均年龄66±18.1岁；9.7%（N = 13）患有IBD，17.9%（N = 24）免疫功能低下。1个月时的早期FMT失败率为19.4%，到3个月时又有3%的患者失败。在验证队列中，低风险患者的FMT失败率为2.1%，中度风险患者为16.1%，高风险患者为35.7%。发育队列中FMT失败的受试者工作特征曲线下面积（AUROC）为0.81，验证队列中为0.84。
严重和严重复杂型指征、FMT期间的住院状态以及先前与CDI相关的住院次数与单次FMT治疗CDI的早期失败密切相关。该新型预测模型在识别FMT治疗后高失败风险个体方面具有良好的辨别力，并可能有助于治疗医生制定后续管理计划。
