Clostridium difficile—Diagnostic and Clinical Challenges

Clostridium difficile is the most common cause of healthcare-associated infection in the US and is increasingly recognized as a pathogen in the community. C. difficile is considered one of the most urgent antibiotic-resistant threats to public health and can cause a variety of clinical manifestations, ranging from asymptomatic colonization, to mild diarrhea, to toxic megacolon and death. C. difficile infection is secondary to dysbiosis, or a condition whereby the microbiota of the gastrointestinal tract is disrupted (often secondary to antimicrobial therapy), creating an environment where C. difficile can flourish and cause a toxin-mediated illness. We have asked 4 experts with different roles in this field to share their thoughts on contemporary challenges in diagnosing, treating, and preventing C. difficile infection.What are some of the challenges in diagnosing Clostridium difficile infection (CDI)6? Larry Kociolek: There are 2 general types of tests to detect C. difficile: (1) tests that detect free toxin, and (2) tests that detect an organism with the potential to produce toxins (i.e., toxigenic strains of C. difficile). Cell culture cytotoxicity neutralization assay and toxigenic stool culture, the gold standards for detection of free toxin and toxigenic strains of C. difficile, respectively, have very limited utility in the clinical setting because of long turnaround times (several days) and excessive labor requirements. Therefore, these assays are primarily used for research. Toxin enzyme immunoassays (EIAs) and nucleic acid amplification tests (NAATs) are the most commonly used tests for C. difficile. Although toxin detection is more specific for CDI (i.e., symptomatic disease), most hospitals have abandoned toxin EIAs because of potentially suboptimal sensitivity and concerns for falsely negative results. NAATs are now the most commonly used diagnostic tests for the detection of C. difficile in US hospitals. NAATs are easy to perform, provide rapid results, and …