Molecular methods in the diagnosis of Clostridium difficile infections: an update

Abstract

Nucleic acid amplification techniques (NAATs) represent a major advance in the diagnosis of Clostridium difficile (C. difficile) infection. This review analyzes the different options available for a molecular diagnosis of C. difficile infection, as well as the strengths and weaknesses of NAATs. The performances of seven commercials NAATs are compared (BD GeneOhm Cdiff, Illumigene C. difficile, Xpert C. difficile, BD Max Cdiff, Portrait Toxigenic C. difficile, ProGastro Cd, Seeplex Diarrhea ACE). The sensitivity and the rapidity of NAATs are excellent: additional efforts should focus on the discrimination between infection and colonization. Reporting the DNA load of toxigenic C. difficile in the stool sample may represent a solution. Diagnostic algorithms combining immunoassays and NAATs could also improve the specificity and reduce the global cost of this analysis.

Keywords::

• clinical severity
• inhibitor rate
• PCR
• toxigenic culture turnaround time

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Nucleic acid amplification techniques (NAATs) must only be performed on diarrheal stools (Bristol stool chart 5–7).

• • NAATs combine excellent positive and negative predictive values, in contrast to enzyme immunoassays (EIA) and glutamate dehydrogenase (GDH) assays.

• • Qualitative NAATs cannot discriminate colonization from infection, but reporting the DNA load of toxigenic C. difficile using quantitative NAATs may add diagnostic value.

• • The only ‘test of cure’ is the resolution of the diarrhea.

• • Positive C. difficile NAATs are difficult to interpret in children before 2 years of age and in inflammatory bowel disease patients.

• • Diagnostic algorithms reduce the cost of NAATs and individualize a subgroup of patients with free toxins in stools, which is more specific of the disease.

• • Even if NAATs are more expensive, this may be counterbalanced by a shorter technical working time and a decrease in costs due to healthcare-associated infections.

Notes