Laboratory diagnostic methods for clostridioides difficile infection

Sammendrag

Introduction. Clostridioides difficile is an anaerobic gram-positive, sporeforming, toxin-producing bacillus that is transmitted among humans through the fecal-oral route, as a result of ingestion of spores. Colonization of C. difficile is prevented by barrier properties of the fecal microbiota; weakening of this resistance by antibiotics is a major risk factor for disease. Toxin production is the key to pathogenesis, which leads to colonocyte death, loss of intestinal barrier function, and neutrophilic colitis. C. difficile infection is one of the most common healthcare-associated infections mainly occurring in developed countries. It is also estimated that 75% of antibiotic-associated colitis cases are caused by C. difficile, and of those, 90–100% are pseudomembranous colitis. In the USA, C. difficile has become a major healthcare problem with an estimated half a million infections and 14.000 deaths each year; which can also cause major economic problems in the healthcare system. Due to the rapid evolution of antibiotic resistance in C. difficile and the consequent effects on the prevention and treatment of C. difficile infection, it is very critical to diagnose patients as soon as possible.

The aime of the study was to carry out an analysis of the performance of current laboratory diagnostic methods for C. difficile infection.

Material and methods. We performed systematic review of studies in PubMed and Web of Science. The following methods were evaluated glutamate dehydrogenase (GDH) enzyme immunoassays (GDH EIAs), toxin A and B detection by enzyme immunoassays (toxin AB EIAs), and nucleic acid amplification tests (NAATs) for C. difficile toxin genes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each method were determinated.

Results. Various methods are used to diagnose C. difficile infection, including detection of glutamate dehydrogenase (GDH) – an antigen secreted by C. difficile – through enzyme immunoassays (GDH EIAs), detection of toxins A or B of C. difficile strains through enzyme immunoassays (toxin AB EIAs), or nucleic acid amplification tests (NAATs) for C. difficile toxin genes. Each assay has advantages and disadvantages and exhibits performance differences. Based on 39 studies, the pooled sensitivities/specificities were 92.7%/94.6%, 57.9%/97.0%, and 90.0%/95.8% for GDH EIAs, toxin AB EIAs, and NAATs, respectively, compared with those of toxigenic culture. The pooled sensitivities of automated EIAs were significantly higher than those of non-automated EIAs for both GDH and toxins A and B. The pooled sensitivity of Xpert C. difficile was significantly higher than those of other NAATs. PPVs increased as C. difficile infection prevalence increased, and NPVs were excellent when C. difficile infection prevalence was low; at C. difficile infection prevalence of 5%, PPV=37%-65% and NPV=97%-100%; at C. difficile infection prevalence of 50%, PPV=92%-97% and NPV=65%-98%.

Conclusions. Accurate diagnosis of C. difficile infection is essential as it guides patient management and infection control practices. The data from this study may be useful for C. difficile infection diagnosis in clinical microbiology laboratories and for clinicians diagnosing and treating C. difficile infection.