Markers of Intestinal Inflammation, Not Bacterial Burden, Correlate With Clinical Outcomes in Clostridium difficile Infection
Markers of Intestinal Inflammation, Not Bacterial Burden, Correlate With Clinical Outcomes in Clostridium difficile Infection
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DOI：
10.1093/cid/cit147
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发表时间：
2013-06-15
影响因子：
11.8
通讯作者：
Haslam, David B.
中科院分区：
文献类型：
--
作者：
El Feghaly, Rana E.;Stauber, Jennifer L.;Haslam, David B.
背景。艰难梭菌是一种主要的医院获得性感染。许多患者在适当的抗生素治疗下症状仍持续数天。为了评估持续感染和持续炎症的影响，我们检查了粪便细胞因子水平、粪便艰难梭菌负担和艰难梭菌感染（CDI）的疾病结局之间的相关性。我们于2011年6月至2012年5月在巴恩斯犹太医院对CDI住院成人进行了一项前瞻性队列研究。我们用酶免疫分析法测定了粪便中白细胞介素8 （IL-8）和乳铁蛋白的浓度。我们采用实时聚合酶链反应（real-time polymerase chain reaction， PCR）技术测定了粪便中IL-8和CXCL-5 RNA转录物的相对丰度，并采用定量PCR技术对艰难梭菌负荷进行计数。在120名研究对象中，101名（84%）开始使用甲硝唑，其中33名（33%）随后使用万古霉素。62例（52%）患者在开始CDI治疗后腹泻持续5天或更长时间。初始粪便CXCL-5信使RNA （mRNA）、IL-8 mRNA和IL-8蛋白与持续性腹泻和万古霉素使用相关。诊断时粪便细胞因子升高的患者腹泻缓解时间较长。粪便细胞因子比临床严重程度评分在识别患者治疗失败风险方面更敏感。艰难梭菌负荷与任何疾病或预后指标均无相关性，甲硝唑和万古霉素均能降低艰难梭菌负荷。CDI患者持续腹泻与肠道炎症有关，而与粪便病原体负担无关。这些发现表明，调节宿主反应，而不是调整抗微生物方案，可能是治疗持续疾病患者更有效的方法。
Background. Clostridium difficile is a leading hospital-acquired infection. Many patients remain symptomatic for several days on appropriate antibiotic therapy. To assess the contribution of ongoing infection vs persistent inflammation, we examined the correlation between fecal cytokine levels, fecal C. difficile burden, and disease outcomes in C. difficile infection (CDI).Methods. We conducted a prospective cohort study in Barnes Jewish Hospital between June 2011 and May 2012 of hospitalized adults with CDI. We determined fecal interleukin 8 (IL-8) and lactoferrin protein concentrations by enzyme immunoassay. We used real-time polymerase chain reaction (PCR) to measure relative fecal IL-8 and CXCL-5 RNA transcript abundances, and quantitative PCR to enumerate C. difficile burden.Results. Of 120 study subjects, 101 (84%) were started on metronidazole, and 33 of those (33%) were subsequently given vancomycin. Sixty-two (52%) patients had diarrhea persistent for 5 or more days after starting CDI therapy. Initial fecal CXCL-5 messenger RNA (mRNA), IL-8 mRNA, and IL-8 protein correlated with persistent diarrhea and use of vancomycin. Time to diarrhea resolution was longer in patients with elevated fecal cytokines at diagnosis. Fecal cytokines were more sensitive than clinical severity scores in identifying patients at risk of treatment failure. Clostridium difficile burden did not correlate with any measure of illness or outcome at any point, and decreased equally with metronidazole and vancomycin.Conclusions. Persistent diarrhea in CDI correlates with intestinal inflammation and not fecal pathogen burden. These findings suggest that modulation of host response, rather than adjustments to antimicrobial regimens, might be a more effective approach to patients with unremitting disease.