Clostridium difficile infection (CDI), which ranges from mild diarrhea to life-threatening colitis, is one of the most common healthcare-associated infections (HAI). CDI causes substantial morbidity, mortality, and increased healthcare expenditures. The CDC recently classified CDI as an “immediate public health threat that requires urgent and aggressive action.” CDI is also increasing among children and is the most common HAI at our children’s hospital with twice the incidence of MRSA. Despite the significant burden and the CDC call to action, studies of CDI epidemiology, diagnosis, treatment, and prevention in children are relatively limited. Diagnosing CDI in children is very challenging. Compared to adults, children are commonly asymptomatic carriers of C. difficile. In asymptomatic carriers, C. difficile harmlessly inhabits the intestinal tract and can be detected in the stool. There are several types of CDI diagnostic tests that differ in sensitivity (Sn) in adult patients. CDI test types most commonly used are nucleic acid amplification tests (NAATs) and toxin enzyme immunoassays (EIAs). NAATs are most commonly used to diagnose CDI at US children’s hospitals. NAATs are highly sensitive and also detect C. difficile in children who are asymptomatic carriers. Because carriage is common in children, NAAT positivity does not necessarily indicate that C. difficile is the cause of a child’s diarrhea. Therefore, CDI misdiagnosis among asymptomatic carriers is a common consequence of using NAATs. In comparison, toxin detection by EIA is more specific for identifying CDI. Despite the specificity (Sp), lower cost and ease of performance of EIAs, children’s hospital preference for NAATs is based on adult studies suggesting suboptimal EIA Sn. However, we surmise that methodological constraints related to inappropriate reference methods in many adult CDI studies may have led to underestimation of EIA Sn. Nonetheless, to overcome the limitations of both NAATs and EIAs, a recently developed ultrasensitive toxin assay is under investigation in adult patients. None of these CDI tests have been well studied in children. More accurate CDI diagnostic approaches are needed in children because the impact of CDI misdiagnosis is substantial. CDI misdiagnosis leads to unnecessary antibiotic utilization for CDI among children who are carriers, increasing healthcare costs, antibiotic resistance, and adverse events. CDI misdiagnosis also biases investigation of pediatric CDI. Therefore, improved CDI diagnostic methods are necessary to improve patient care for this common HAI and reduce misclassification bias in future CDI investigation in children. To optimize CDI diagnosis in children, the proposed study will comprehensively evaluate various laboratory methodologies to better differentiate CDI and carriage. In addition, using whole genome sequencing (WGS), we aim to identify differences between strains causing CDI and carriage. WGS will augment our understanding of CDI pathogenesis in children and may reveal genomic targets unique to strains causing carriage or CDI that can be adapted for CDI diagnostic testing.
|Effective start/end date||2/1/17 → 1/31/21|
- Ann & Robert H. Lurie Children's Hospital of Chicago (001507-NU-02 // 5K23AI123525-04)
- National Institute of Allergy and Infectious Diseases (001507-NU-02 // 5K23AI123525-04)
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