High proportion of false-positive Clostridium difficile enzyme immunoassays for toxin A and B in pediatric patients.
OBJECTIVE
To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity.


METHODS
Nested case-control.


METHODS
Two tertiary care pediatric hospitals.


METHODS
As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays.


RESULTS
Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%-7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii.


CONCLUSIONS
Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.
Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA. pxt2@case.edu
Philip
P
Toltzis
Michelle M
MM
Nerandzic
Elie
E
Saade
Mary Ann
MA
O'Riordan
Sarah
S
Smathers
Theoklis
T
Zaoutis
Jason
J
Kim
Curtis J
CJ
Donskey
D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics; D001427:Bacterial Toxins / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D003015:Clostridium Infections / Q000175:diagnosis*; D004269:DNA, Bacterial / Q000032:analysis; D004768:Enterotoxins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile