Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients.
Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients.
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DOI：
10.1128/msphere.00936-20
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发表时间：
2021-01-13
期刊：
影响因子：
4.8
通讯作者：
Dubberke ER
中科院分区：
文献类型：
--
作者：
Fishbein SRS;Hink T;Reske KA;Cass C;Struttmann E;Iqbal ZH;Seiler S;Kwon JH;Burnham CA;Dantas G;Dubberke ER
目前尚不存在诊断艰难梭菌感染（CDI）的金标准。一个有争议的领域是如何管理粪便核酸扩增检测阳性但毒素酶免疫检测阴性的患者。艰难梭菌感染（CDI）最常使用核酸扩增试验（NAAT）进行诊断;这些试验的阳性预测值较低，导致患者定植有C。不必要地接受CDI治疗抗生素。抗生素治疗在此类病例中的风险和益处尚不清楚。在随机分配至万古霉素组（n = 8）或安慰剂组（n = 7）之前、期间和之后，采集NAAT阳性、毒素酶免疫测定（EIA）阴性患者的粪便样本。C.从粪便和环境样品中选择性地培养艰难梭菌和耐药性微生物（ARO）。鸟枪宏基因组学和比较分离株基因组学用于了解口服万古霉素对微生物组和环境污染的影响。总体而言，80%的安慰剂组患者和71%的万古霉素组患者被C.后处理困难。随机分配至安慰剂组的1例患者随后接受了CDI治疗。万古霉素治疗组β-多样性（P = 0.0059）和大环内酯-林可酰胺-链阳性菌素（MLS）耐药基因（P = 0.037）增加;分别在53%的患者和26%的患者中发现了艰难梭菌和万古霉素耐药肠球菌（VRE）环境污染。我们发现万古霉素改变了肠道微生物群，不能永久清除C。艰难梭菌，并与VRE定植/环境污染有关。(This研究已在ClinicalTrials.gov注册，注册号为NCT 03388268）。目前尚不存在诊断艰难梭菌感染（CDI）的金标准。一个有争议的领域是如何管理粪便核酸扩增检测阳性但毒素酶免疫检测阴性的患者。现有数据表明，这些患者中的大多数没有CDI，但大多数接受口服万古霉素治疗。治疗的潜在益处包括如果患者确实患有CDI，则不良结局的风险降低，以及降低C的可能性。难以脱落/传播。然而，口服万古霉素扰乱肠道微生物群，促进耐药微生物定植/传播。我们进行了一项双盲随机对照试验，以评估口服万古霉素治疗在这一人群中的风险效益。口服万古霉素不能长期清除C。艰难梭菌，扰乱微生物群，并与万古霉素耐药肠球菌的定植/脱落有关。这项工作强调了需要更好地了解这一人群的患者在C。艰难梭菌/ARO相关结局和传播。
A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Clostridioides difficile infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with C. difficile unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin (n = 8) or placebo (n = 7). C. difficile and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with C. difficile posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity (P = 0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes (P = 0.037) increased after treatment; C. difficile and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear C. difficile, and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.) IMPORTANCE A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease C. difficile shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of C. difficile, perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of C. difficile/ARO-related outcomes and transmission.