Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, Alberta, Canada.
Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Alberta, Canada.
Clin Infect Dis. 2021 Nov 2;73(9):e2673-e2679. doi: 10.1093/cid/ciaa1553.
Clostridioides difficile infection (CDI) is an opportunistic disease that lacks a gold-standard test. Nucleic acid amplification tests such as real-time polymerase chain reaction (PCR) demonstrate an excellent limit of detection (LOD), whereas antigenic methods are able to detect protein toxin. Latent class analysis (LCA) provides an unbiased statistical approach to resolving true disease.
A cross-sectional study was conducted in patients with suspected CDI (N = 96). Four commercial real-time PCR tests, toxin antigen detection by enzyme immunoassay (EIA), toxigenic culture, and fecal calprotectin were performed. CDI clinical diagnosis was determined by consensus majority of 3 experts. LCA was performed using laboratory and clinical variables independent of any gold standard.
Six LCA models were generated to determine CDI probability using 4 variables including toxin EIA, toxigenic culture, clinical diagnosis, and fecal calprotectin levels. Three defined zones as a function of real-time PCR cycle threshold (Ct) were identified using LCA: CDI likely (>90% probability), CDI equivocal (<90% and >10%), CDI unlikely (<10%). A single model comprising toxigenic culture, clinical diagnosis, and toxin EIA showed the best fitness. The following Ct cutoffs for 4 commercial test platforms were obtained using this model to delineate 3 CDI probability zones: GeneXpert®: 24.00, 33.61; Simplexa®: 28.97, 36.85; Elite MGB®: 30.18, 37.43; and BD Max™: 27.60, 34.26.
The clinical implication of applying LCA to CDI is to report Ct values assigned to probability zones based on the commercial real-time PCR platform. A broad range of equivocation suggests clinical judgment is essential to the confirmation of CDI.
艰难梭菌感染（CDI）是一种机会性疾病，缺乏金标准检测。核酸扩增检测，如实时聚合酶链反应（PCR），具有出色的检测限（LOD），而抗原方法能够检测蛋白毒素。潜在类别分析（LCA）提供了一种公正的统计方法来确定真实的疾病。
对疑似 CDI 患者（N=96）进行了横断面研究。进行了四项商业实时 PCR 检测、酶联免疫吸附试验（EIA）检测毒素抗原、产毒培养和粪便钙卫蛋白检测。CDI 临床诊断由 3 位专家的共识多数决定。使用独立于任何金标准的实验室和临床变量进行 LCA。
使用包括 EIA、产毒培养、临床诊断和粪便钙卫蛋白水平在内的 4 个变量，生成了 6 个 LCA 模型来确定 CDI 概率。LCA 确定了三个与实时 PCR 循环阈值（Ct）相关的区域：CDI 可能性大（>90%概率）、CDI 不确定（<90%和>10%）、CDI 可能性小（<10%）。一个包含产毒培养、临床诊断和毒素 EIA 的单一模型显示出最佳的拟合度。使用该模型获得了以下用于划分 3 个 CDI 概率区的 4 个商业检测平台的 Ct 截止值：GeneXpert®：24.00、33.61；Simplexa®：28.97、36.85；Elite MGB®：30.18、37.43；和 BD Max™：27.60、34.26。
将 LCA 应用于 CDI 的临床意义是报告基于商业实时 PCR 平台分配给概率区的 Ct 值。广泛的不确定性表明临床判断对于 CDI 的确认至关重要。
