<i>Clostridium difficile</i> Infection in Infants and Children

Schutze, Gordon E.; Willoughby, Rodney E.

doi:10.1542/peds.2012-2992

Cited by 226 publications

(119 citation statements)

References 28 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…The American Academy of Pediatrics does not recommend routine testing for C. difficile in children Ͻ1 year of age and suggests that positive C. difficile results be interpreted with suspicion in children Ͻ3 years old (60). In this study, toxigenic C. difficile was identified in 40.5% (49 of 121) of the stool specimens from infants under the age of one.…”

Section: Discussionmentioning

confidence: 66%

Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis

et al. 2015

View full text Add to dashboard Cite

fThe appropriate treatment and control of infectious gastroenteritis depend on the ability to rapidly detect the wide range of etiologic agents associated with the disease. Clinical laboratories currently utilize an array of different methodologies to test for bacterial, parasitic, and viral causes of gastroenteritis, a strategy that suffers from poor sensitivity, potentially long turnaround times, and complicated ordering practices and workflows. Additionally, there are limited or no testing methods routinely available for most diarrheagenic Escherichia coli strains, astroviruses, and sapoviruses. This study assessed the performance of the FilmArray Gastrointestinal (GI) Panel for the simultaneous detection of 22 different enteric pathogens directly from stool specimens: Campylobacter spp., Clostridium difficile (toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibrio spp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx 1 and stx 2 ) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus. Prospectively collected stool specimens (n ‫؍‬ 1,556) were evaluated using the BioFire FilmArray GI Panel and tested with conventional stool culture and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100% for 12/22 targets and >94.5% for an additional 7/22 targets. For the remaining three targets, sensitivity could not be calculated due to the low prevalences in this study. The FilmArray GI Panel specificity was >97.1% for all panel targets. The FilmArray GI Panel provides a comprehensive, rapid, and streamlined alternative to conventional methods for the etiologic diagnosis of infectious gastroenteritis in the laboratory setting. The potential advantages include improved performance parameters, a more extensive menu of pathogens, and a turnaround time of as short as 1 h. Infectious gastroenteritis (IGE) is a leading cause of global morbidity and mortality. It is estimated that IGE contributes to the death of 2,195 children each day (1). IGE also contributes to serious morbidities, such as malnutrition, stunting, and impaired cognitive function (2, 3). Diarrheal disease disproportionately affects developing nations, but IGE remains a significant problem in industrialized countries as well. For example, it is estimated that each year, approximately 178.8 million cases of gastrointestinal illness occur in the United States, resulting in 474,000 hospitalizations and 5,000 deaths (4). Although the etiologic agents responsible for about 80% of these illnesses are unidentified or otherwise unspecified (4), norovirus and Salmonella spp. are currently the most commonly identified pathogens associated with food-borne disease in the United States and account for 5.5 and 1.0 million cases each year, resp...

show abstract

Section: Discussionmentioning

confidence: 66%

Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Toxigenic culture (TC) is the most widely recognized laboratory gold standard for the diagnosis of CDI (2,4), and thus our sample size calculations were built around the TC results. Our goal was to estimate digital ELISA sensitivities and specificities with a margin of error (determined by 95% confidence interval) for each of Ͻ10%.…”

Section: Methodsmentioning

confidence: 99%

“…he recent increases in the global incidence and severity of Clostridium difficile infection (CDI) (1-3) are of major concern, and CDI now consumes substantial resources for diagnosis, treatment, and infection control (2,4). A recent U.S. prevalence survey of health care-associated infections (HAI) (5) found that C. difficile was the most commonly reported pathogen, causing 12.1% of HAI.…”

mentioning

confidence: 99%

Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in Stool

et al. 2015

View full text Add to dashboard Cite

The currently available diagnostics for Clostridium difficile infection (CDI) have major limitations. Despite mounting evidence that toxin detection is paramount for diagnosis, conventional toxin immunoassays are insufficiently sensitive and cytotoxicity assays too complex; assays that detect toxigenic organisms (toxigenic culture [TC] and nucleic acid amplification testing [NAAT]) are confounded by asymptomatic colonization by toxigenic C. difficile. We developed ultrasensitive digital enzymelinked immunosorbent assays (ELISAs) for toxins A and B using single-molecule array technology and validated the assays using (i) culture filtrates from a panel of clinical C. difficile isolates and (ii) 149 adult stool specimens already tested routinely by NAAT. The digital ELISAs detected toxins A and B in stool with limits of detection of 0.45 and 1.5 pg/ml, respectively, quantified toxins across a 4-log range, and detected toxins from all clinical strains studied. Using specimens that were negative by cytotoxicity assay/TC/NAAT, clinical cutoffs were set at 29.4 pg/ml (toxin A) and 23.3 pg/ml (toxin B); the resulting clinical specificities were 96% and 98%, respectively. The toxin B digital ELISA was 100% sensitive versus cytotoxicity assay. Twenty-five percent and 22% of the samples positive by NAAT and TC, respectively, were negative by the toxin B digital ELISA, consistent with the presence of organism but minimal or no toxin. The mean toxin levels by digital ELISA were 1.5-to 1.7-fold higher in five patients with CDI-attributable severe outcomes, versus 68 patients without, but this difference was not statistically significant. Ultrasensitive digital ELISAs for the detection and quantification of toxins A and B in stool can provide a rapid and simple tool for the diagnosis of CDI with both high analytical sensitivity and high clinical specificity.T he recent increases in the global incidence and severity of Clostridium difficile infection (CDI) (1-3) are of major concern, and CDI now consumes substantial resources for diagnosis, treatment, and infection control (2, 4). A recent U.S. prevalence survey of health care-associated infections (HAI) (5) found that C. difficile was the most commonly reported pathogen, causing 12.1% of HAI. Despite available therapies, treatment failure and recurrence are common (1, 2, 6). The emergence of epidemic strains capable of toxin hyperproduction and increased disease severity/mortality (2, 7, 8) has further increased the urgency to improve methods for diagnosis and treatment. Accurate diagnosis remains the cornerstone of effective management.Disease caused by C. difficile infection is due to the effects of two large protein exotoxins, toxins A and B (9, 10). While the presence of toxin is necessary to cause disease, the optimal method for diagnosing CDI remains controversial. Appropriate patient selection can improve diagnostic accuracy for all assays (2, 11). The classic gold standard stool assay, toxigenic culture (TC), is complex, lengthy, and unstandardized; furthermore, it is...

show abstract

“…With a recurrence of symptoms, repeat testing should not be performed before 4 weeks after the initial positive test result. A specific testing methodology is not clearly endorsed; however, NAAT is mentioned as the most sensitive method for the detection of the organism (35). The guidelines do acknowledge that there are not enough published data to assess the diagnosis of disease in children with a NAAT alone (35).…”

Section: Guidelines Addressing C Difficile Infection: General Testinmentioning

confidence: 99%

“…The study results raise concerns about the use of toxin EIAs in the diagnosis of CDI in children due to the high rates of false positives; however, this seems in contrast with other publications demonstrating a lack of sensitivity with EIAs (39). The AAP guidelines also question the usefulness of EIAs in the pediatric population due to poor performance characteristics and the low positive predictive value (35).…”

Section: Difficile Diagnostic Testsmentioning

confidence: 99%

Diagnosis of Clostridium difficile Infections in Children

Antonara

Leber

2016

J Clin Microbiol

View full text Add to dashboard Cite

The detection and diagnosis of Clostridium difficile infection in pediatric populations have some unique considerations in comparison to testing in adults. The testing methodologies, including toxigenic culture, cell cytotoxicity, antigen detection, and, more recently, molecular testing, are the same in all age groups. However, limited data exist on the specific performance characteristics in children. In this review, we focus on the challenges of testing in pediatric populations and assess the available data on test performance in these populations. Additionally, a review of the existing guidance for testing is provided.

show abstract

Clostridium difficile Infection in Infants and Children

Cited by 226 publications

References 28 publications

Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis

Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis

Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in Stool

Diagnosis of Clostridium difficile Infections in Children

Contact Info

Product

Resources

About