Swale Andrew, Miyajima Fabio, Roberts Paul, Hall Amanda, Little Margaret, Beadsworth Mike B J, Beeching Nick J, Kolamunnage-Dona Ruwanthi, Parry Chris M, Pirmohamed Munir
The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, United Kingdom; The Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, United Kingdom.
The Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, United Kingdom.
PLoS One. 2014 Aug 29;9(8):e106118. doi: 10.1371/journal.pone.0106118. eCollection 2014.
Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded. Specimens were subject to microbiological culture and PCR-ribotyping. Levels of faecal calprotectin (FC) and lactoferrin (FL) were measured by ELISA. Statistical analysis was conducted using percentile categorisation. ROC curve analysis was employed to determine optimal cut-off values. Both markers were highly correlated with each other (r2 = 0.74) and elevated in cases compared to controls (p<0.0001; ROC>0.85), although we observed a large amount of variability across both groups. The optimal case-control cut-off point was 148 mg/kg for FC and 8.1 ng/µl for FL. Median values for FL in CDI cases were significantly greater in patients suffering from severe disease compared to non-severe disease (104.6 vs. 40.1 ng/µl, p = 0.02), but were not significant for FC (969.3 vs. 512.7 mg/kg, p = 0.09). Neither marker was associated with 90-day recurrence, prolonged CDI symptoms, positive culture results and colonisation by ribotype 027. Both FC and FL distinguished between CDI cases and AAD controls. Although FL was associated with disease severity in CDI patients, this showed high inter-individual variability and was an isolated finding. Thus, FC and FL are unlikely to be useful as biomarkers of complicated CDI disease.
粪便中钙卫蛋白和乳铁蛋白的检测已成功用于区分功能性和炎症性肠病，但艰难梭菌感染（CDI）方面的证据有限。我们前瞻性招募了164例CDI病例和52例抗生素相关性腹泻（AAD）对照。记录了疾病严重程度、症状持续时间、30天死亡率和90天复发率等复杂CDI标志物的信息。标本进行了微生物培养和PCR核糖体分型。采用酶联免疫吸附测定法（ELISA）检测粪便钙卫蛋白（FC）和乳铁蛋白（FL）水平。使用百分位数分类进行统计分析。采用ROC曲线分析确定最佳临界值。尽管我们观察到两组间存在大量变异性，但两种标志物彼此高度相关（r2 = 0.74），且病例组高于对照组（p<0.0001；ROC>0.85）。FC的最佳病例对照临界值为148 mg/kg，FL为8.1 ng/µl。与非重症疾病患者相比，重症疾病CDI病例的FL中位数显著更高（104.6对40.1 ng/µl，p = 0.02），但FC无显著差异（969.3对512.7 mg/kg，p = 0.09）。两种标志物均与90天复发、CDI症状延长、培养结果阳性和027核糖体分型定植无关。FC和FL均可区分CDI病例和AAD对照。尽管FL与CDI患者的疾病严重程度相关，但个体间差异很大，且是一个孤立发现。因此，FC和FL不太可能作为复杂CDI疾病的生物标志物。
