Restriction endonuclease analysis of stool culture isolates from children with multiple episodes of Clostridium difficile infection demonstrates some unexpectedly long intervals to relapse with the initial infecting strain
Background: The incidence of pediatric Clostridium difficile infection (CDI) is increasing, and up to 25% of children with CDI experience a recurrence. Recurrent CDI results from relapse with the original infecting strain or reinfection with a new strain. Current standardized CDI definitions classify a subsequent infection as new or recurrent if it occurs > 8 weeks or ≤ 8 weeks after the original infection, respectively.
Methods: Saved C. difficile toxin B gene PCR-positive stool specimens at an academic children's hospital were cultured and typed by restriction endonuclease analysis (REA). REA patterns of consecutive C. difficile isolates from patients with multiple CDI episodes were compared to differentiate relapse (infection with the same strain) from reinfection (infection with a new strain) irrespective of the time interval between infections.
Results: Two or more saved stool specimens were identified from 40 children diagnosed with CDI between 4/2011 and 12/2013. Among the 55 paired specimens, 13 were not evaluable because C. difficile culture from either the initial and/or subsequent CDI episode was negative. Among the 42 remaining paired specimens, REA demonstrated the same C. difficile strain from a greater proportion of stool cultures collected within 26 weeks of the initial infection compared to those that recurred after 26 weeks (23/34 [68%] vs 1/8 [13%], p=0.01; Figure). Strain DH was isolated from the initial stool of 9 paired specimens and from the subsequent stool from 8 (89%) of those pairs. Of those 8 DH CDI relapses, 4 (50%) occurred after 8 weeks and up to 48 weeks after the original infection.
Conclusion: Relapses with the same strain as the initial infection accounted for the majority of subsequent CDI episodes within 26 weeks after infection, suggesting that the definition of recurrence may need to be extended beyond 8 weeks. Strain DH, the predominant strain in this cohort, accounted for half of relapses occurring after 8 weeks. Defining recurrent CDI as that occurring only within 8 weeks of the original infection may lead to misclassification of some recurrent CDI as new CDI episodes, although infections after reacquisition of the same initial C. difficile strain cannot be definitively ruled out.
Figure: Time Interval Between CDI Episodes
Merck: Grant Investigator, Grant recipient
Actellion: Board Member, Consulting fee
Merck: Board Member, Consulting fee
Rebiotix: Board Member, Consulting fee
Viropharma: Consultant, Consulting fee
Summit: Consultant, Consulting fee
Viropharma: patent holder, patent
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