Clostridium difficile: Diagnosis and the Consequence of Over Diagnosis

Abstract

Clostridium difficile infection (CDI) is a leading cause of healthcare-associated infections, accounting for significant disease burden and mortality. The clinical spectrum of C. difficile ranges from asymptomatic colonization to toxic megacolon and fulminant colitis. CDI is characterized by new onset of C 3 unformed stools in 24 h and is confirmed by laboratory test for the presence of toxigenic C. difficile. Currently, laboratory tests to diagnose CDI include toxigenic culture, glutamate dehydrogenase (GDH), nucleic acid amplification test (NAAT), and toxins A/B enzyme immunoassay (EIA). The sensitivities of these tests are variable with toxin EIA ranging from 53 to 60% and with NAAT at about 95%. Overall, the specificity is [ 90% for these methods. However, the positive predictive value (PPV) depends on the disease prevalence with lower CDI rates associated with lower PPVs.Notably, the widespread use of the highly sensitive NAAT and its relatively lower clinical specificity have led to overdiagnosis of C. difficile by identifying carriers when NAAT is used as the sole diagnostic method. Overdiagnosis of C. difficile has resulted in unwarranted treatment, possibly attributing to resistance to metronidazole and vancomycin, increased risk for overgrowth of vancomycin-resistant enterococci strains in stool specimens, and increased hospitalization thereby impacting patient safety and healthcare costs.Strategies to optimize the clinical sensitivity and specificity of current laboratory tests are critical to differentiate the clinical CDI from colonization. To achieve high diagnostic yield, if preagreed institutional criteria for stool submission are not used, a multistep approach to CDI diagnosis is recommended, such as either GDH or NAAT followed by toxins A/B EIA in conjunction with laboratory stewardship by evaluating C. difficile test orders for appropriateness and providing feedback. Furthermore, antimicrobial stewardship, along with provider education on appropriate testing for C. difficile, is vital to differentiate CDI from colonization.

C. difficilemay be overdiagnosed in adults and is a prevalent commensal in infants

“…Diarrheal symptoms, often the initial diagnostic prompt, are not specific to CDI [48][49][50][51] and pseudomembranous colitis, long thought to be characteristic (and often eponymously referred to as "C. difficile colitis"), may indeed be caused by other enteropathogens, such as C. innocuum or E. coli 8,9,52 . Additional challenges include the large variability in sensitivity and specificity in diagnostic laboratory tests 40,[53][54][55][56][57][58][59][60][61][62] , contradicting results between cultivation and toxin detection assays 63 and an excessive reliance on single molecular tests 64 . Recommended guidelines discourage stand-alone tests for CDI diagnosis and recommend a two-step procedure 53,57 , but due to costs, test availability, capacity and turnaround times, diagnostic algorithms vary between hospitals and often deviate from recommended procedures 58 .…”

Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

“…We analyzed data from this period because on March 1, 2020, the Clinical Hospital for Infectious Disease Iasi was declared a COVID-19 Unit, and as a result the Institute of Gastroenterology and Hepatology was designated the clinic to hospitalize patients with CDI. The diagnosis of CDI was based on the presence of diarrhea (≥ 3 watery stools within 24 h) associated with detection of C. difficile toxin A or B (by enzyme immunoassay) in stool samples[ 19 ]. Hospital-acquired CDI was defined as a stool sample positive for C. difficile toxin(s) at least 72 h after hospital admission.…”

The Role of CD4+ T Cells and Microbiota in the Pathogenesis of Asthma

“…Bacteria that exert harmful effects with respect to asthma include pathogens of the genera Clostridium , Staphylococcus and Pseudomonas . Under certain conditions, these harmful bacteria reportedly exacerbate enterocolitis and pneumonia [ 109 , 110 ]. Additionally, colonization by harmful bacteria reportedly increases the risk of asthma development [ 16 ].…”