Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.
Clin Infect Dis. 2013 Jun;56(12):1713-21. doi: 10.1093/cid/cit147. Epub 2013 Mar 13.
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).
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.
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.
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.
艰难梭菌是一种主要的医院获得性感染。许多患者在接受适当的抗生素治疗后仍会出现数天的症状。为了评估持续感染与持续炎症的关系，我们研究了艰难梭菌感染（CDI）患者粪便细胞因子水平、粪便艰难梭菌负荷与疾病结局之间的相关性。
我们在 2011 年 6 月至 2012 年 5 月期间对巴恩斯犹太医院的住院 CDI 成人患者进行了前瞻性队列研究。我们通过酶联免疫吸附法测定粪便白细胞介素 8（IL-8）和乳铁蛋白蛋白浓度。我们使用实时聚合酶链反应（PCR）来测量粪便中 IL-8 和 CXCL-5 RNA 转录物的相对丰度，并使用定量 PCR 来计数艰难梭菌负荷。
在 120 例研究对象中，有 101 例（84%）患者开始使用甲硝唑，其中 33 例（33%）随后使用万古霉素。62 例（52%）患者在开始 CDI 治疗后 5 天以上仍有腹泻。初始粪便 CXCL-5 信使 RNA（mRNA）、IL-8 mRNA 和 IL-8 蛋白与持续腹泻和万古霉素的使用相关。在诊断时粪便细胞因子升高的患者中，腹泻缓解的时间更长。粪便细胞因子比临床严重程度评分更能识别有治疗失败风险的患者。在任何时间点，艰难梭菌负荷都与任何疾病或结局指标均无相关性，并且与甲硝唑和万古霉素的使用都呈等量下降。
CDI 中的持续性腹泻与肠道炎症而不是粪便病原体负荷有关。这些发现表明，宿主反应的调节可能是治疗持续疾病患者的更有效方法，而不是调整抗菌药物治疗方案。
