Current knowledge on the laboratory diagnosis of Clostridium difficile infection

Abstract

Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.

Keywords: Clostridium difficile, Toxigenic culture, Nucleic acid amplification tests, Enzyme immunoassay, Diagnosis, Glutamate dehydrogenase

Core tip: This work is a review of the strategies that may be used for laboratory diagnosis of infection with Clostridium difficile. First, we provide general recommendations for testing of samples taking in account the guidelines of the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America and the American College of Gastroenterology. We reviewed diverse methods of diagnosis including, culture, toxigenic culture, cell cytotoxic neutralization assay and the use of enzyme immuno assays. Finally, we present an overview of singleplex and multiplex nucleic acid amplification tests.