Advances and required improvements in methods to diagnosing Clostridioides difficile infections in the healthcare setting

ABSTRACT

Introduction

Clostrididioides difficile is associated with adverse clinical outcomes and increased morbidity, mortality, length of hospital stay, and health-care costs.

Areas Covered: We searched relevant papers in PubMed for the last 10 years. In major papers, we scanned the bibliographies to ensure that important articles were included. This review addresses the evolving epidemiology of Clostridioides difficile infection (CDI) and discusses novel methods/approaches for improving the diagnosis of this important disease.

Expert opinion

No single diagnostic test to date has demonstrated optimum sensitivity and specificity for detection of CDI. Many institutions have developed multi-step algorithms consistent with guidelines established by various professional societies. Some institutions have successfully tried to improve the pretest probability of molecular assays by implementing appropriate sample rejection criteria and establishing best practice alerts at the time of electronic order entry. Others have established PCR cycle threshold cutoffs to attempt to differentiate symptomatic patients from asymptomatic carriers or to make predictions about severity of disease with variable success. As research advances our understanding of C. difficile pathogenesis and pathophysiology, more information on CDI specific biomarkers is emerging. Finally, assessments of the microbiome and metabolome may expand the diagnostic armamentarium with advances in mass spectrometry and sequencing technologies.

KEYWORDS:

• Colitis
• Clostridioides difficile
• two step algorithm
• nucleic acid test
• toxin enzyme immunoassay
• biomarkers
• glutamate dehydrogenase
• best practice alerts
• microbiome
• metabolomics

Declaration of interest

K Carroll has received research funding from BD Diagnostics, Inc. and Singulex, Inc. both of whom manufacture assays for C.difficile testing. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Clostridioides difficile remains a significant cause of healthcare associated diarrhea.

• Rates of CDI have begun to decline, likely related to reduction in fluoroquinolone use through successful antimicrobial stewardship programs.

• As no single diagnostic test to date has demonstrated optimum sensitivity and specificity, multi-step algorithms are recommended by various professional societies’ guidelines.

• Strategies to improve the predictive value of NAATs include implementation of best practice alerts with test rejection if diarrhea can be linked to current laxative use.

• Biomarkers and cytokines may be useful in predicting severity of disease and remain a focus of research.

• Future novel diagnostic methods may make use of observed changes in microbiome profiles by using metabolomics to measure volatile ad non-volatile organic compounds.

Additional information

Funding

This paper was not funded.