The role of glutamate dehydrogenase for the detection of Clostridium difficile in faecal samples: a meta-analysis

Clostridium difficile causes a serious, occasionally fatal, hospital-acquired infection. The laboratory diagnosis of C. difficile infection (CDI) needs to be accurate to ensure optimal patient management, infection control and reliable surveillance. Commercial enzyme-linked immunosorbent assays for C. difficile toxins have poor sensitivity when compared with cell culture cytotoxin assay (CTA) and toxigenic culture (TC). We performed a meta-analysis of the role of glutamate dehydrogenase (GDH) in diagnosis of CDI. We analysed 21 papers, of which eight were excluded. We included publications of original research that used a 'gold standard' reference test (either CTA or TC). We also included publications that used culture without toxin testing of the isolate as a reference test even though this is not recognised as a gold standard. Exclusion criteria were failure to use a gold standard reference test and where the index test was used as the gold standard. Significant heterogeneity between study results justified the summary receiver operating characteristic (SROC) analysis. The meta-analysis demonstrated high diagnostic accuracy of GDH for the presence of C. difficile in faeces; when compared with culture it achieved a sensitivity and specificity of >90%. The SROC plot confirmed this finding. As a surrogate for toxigenic strains the GDH yields a specificity of 80-100% with a false positivity rate of ∼20%, as it detects toxigenic and non-toxigenic strains of the organism. However, GDH test has high sensitivity and negative predictive value and would be a powerful test in a dual testing algorithm when combined with a test to detect toxin.