Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies

Abstract

The increasing incidence of Clostridium difficile infection (CDI) in paediatric hospitalised populations, combined with the emergence of hypervirulent strains, community-acquired CDI and the need for prompt treatment and infection control, makes the rapid, accurate diagnosis of CDI crucial. We validated commonly used C. difficile diagnostic tests in a paediatric hospital population. From October 2011 to January 2012, 150 consecutive stools were collected from 75 patients at a tertiary paediatric hospital in Perth, Western Australia. Stools were tested using: C. Diff Quik Chek Complete, Illumigene C. difficile, GeneOhm Cdiff, cycloserine cefoxitin fructose agar (CCFA) culture, and cell culture cytotoxin neutralisation assay (CCNA). The reference standard was growth on CCFA or Cdiff Chromagar and PCR on isolates to detect tcdA, tcdB, cdtA, and cdtB. Isolates were PCR ribotyped. The prevalence of CDI was high (43 % of patients). Quik Chek Complete glutamate dehydrogenase (GDH) demonstrated a low negative predictive value (NPV) (93 %). Both CCNA and Quik Chek Complete toxin A/B had poor sensitivity (33 % and 29 % respectively). Molecular methods both had 89 % sensitivity. Algorithms using GDH + Illumigene or GeneOhm reduced the sensitivity to 85 % and 83 % respectively. Ribotype UK014/20 predominated. GDH NPV and GeneOhm and Illumigene sensitivities were reduced compared with adult studies. Quik Chek Complete and CCNA cannot reliably detect toxigenic CDI. A GDH first algorithm showed reduced sensitivity. In a high prevalence paediatric population, molecular methods alone are recommended over the use of GDH algorithm or culture and CCNA, as they demonstrate the best test performance characteristics.

Pitfalls in Diagnosis of Pediatric Clostridium difficile Infection

“…31 These tests have not been evaluated extensively in exclusively pediatric samples. [46][47][48] When they have, the sensitivity and specificity values are similar to those documented for adults, although 1 survey conducted in a large pediatric tertiary care center found an unusually low sensitivity for GDH compared with CCTA (81%). 48 Similar to adult specimens, pediatric stool subjected to different CDI diagnostic tests may yield discordant results; specimens that are positive by NAAT but negative by other tests likewise usually do not reflect CDI-consistent disease 46 and probably represent colonization.…”

“…48 Similar to adult specimens, pediatric stool subjected to different CDI diagnostic tests may yield discordant results; specimens that are positive by NAAT but negative by other tests likewise usually do not reflect CDI-consistent disease 46 and probably represent colonization. Hart and colleagues 47 assessed C difficile diagnostic test performances in 150 consecutive pediatric stool specimens and compared these values with those derived in 3 other studies in children. As in adults, toxin EIA had a measured sensitivity of only 35% to 56%.…”

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach

“…A limitation to our study is the small sample size (191 samples), and the exclusion of pediatric stool samples due to limited sample volume. The low sensitivity and NPV of GDH assay in pediatric population has been reported . It means that more confirmatory tests would be needed for pediatric samples under C. diff Quik Chek Complete/Xpert CD algorithm.…”

Diagnosis of Clostridium difficile Infections in Children

“…The 2-step algorithms (GDHϩPCR) showed reduced sensitivity compared to that of a NAAT alone (83% versus 89%). The authors postulate that this difference is probably due to the high prevalence of CDI in their patient population (mainly hematology/oncology patients), and they recommend the use of NAAT alone in high-risk patients (42). In another study comparing the illumigene and Quidel AmpliVue (Quidel Molecular, San Diego, CA) assays in a large number of pediatric patients, both tests performed similarly, suggesting that these tests can be used with this patient population.…”