Clostridium difficile whole genome sequencing reveals limited transmission among symptomatic children: A single-center analysis

Larry K. Kociolek*, Dale N. Gerding, Robyn O. Espinosa, Sameer J. Patel, Stanford T. Shulman, Egon A. Ozer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background Although pediatric Clostridium difficile infections (CDIs) are increasing, C. difficile transmission patterns among children are poorly understood. Methods We performed whole genome sequencing (WGS) on C. difficile isolates collected from children diagnosed with CDI between December 2012 and December 2013 at a single academic medical center. Genome sequences of isolates from CDIs diagnosed ≥8 weeks after study initiation were compared to all study isolate genome sequences. Among patients with isogenic isolates (≤2-3 core genome single nucleotide variants [SNVs] identified by pairwise SNV analyses), common inpatient and/or outpatient healthcare exposures were investigated. Results Among 131 CDIs in 107 children, WGS identified 104 genetically distinct isolates. Of 84 incident CDIs occurring ≥8 weeks after study initiation, only 10 (11.9%) were caused by a strain isogenic to another cohort CDI isolate (putative transmission events). Proportions of each CDI class putatively associated with transmission were hospital-onset healthcare facility-associated (HCFA), 2/16 (12.5%); community-onset HCFA, 1/17 (5.9%); indeterminate, 1/11 (9.1%); community-associated (CA), 5/40 (12.5%); and recurrent, 1/21 (4.8%). Transmission events among CA and HCFA CDIs were similarly infrequent (5/40 [12.5%] vs 3/33 [9.1%]; P =.64). Shared healthcare facility exposures were only identified among 7/10 putative transmission events. Potential community transmission (same postal code) was not identified. Conclusions WGS identified a highly diverse group of C. difficile isolates among children with CDI, including those with HCFA CDI. Clostridium difficile transmission among symptomatic children was very uncommon. Among putatively transmitted cases, investigation of shared healthcare exposures often did not identify a potential transmission source.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalClinical Infectious Diseases
Volume67
Issue number2
DOIs
StatePublished - Jul 2 2018

Funding

Financial support. This work was supported by grants from the Thrasher Research Fund (Early Career Award 11854 to L. K. K.), the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (K23 AI123525 to L. K. K.), and the American Cancer Society (MRSG-13-220-01 to E. A. O.). Research reported in this publication was supported, in part, by the NIH’s National Center for Advancing Translational Sciences (grant UL1TR001422). Potential conflicts of interest. L. K. K. is a scientific advisor for Actelion and has received research supplies from Alere. L. K. K. and S. J. P. have received research grants from Merck and Cubist. D. N. G. holds patents for the prevention of Clostridium difficile infection; is a consultant for Sanofi Pasteur, DaVolterra, MGB, and Pfizer; and is an advisory board member of Merck, Rebiotix, Summit, and Actelion. E. A. O is a scientific advisor for Gladius Pharmaceuticals. All remaining authors: No reported conflicts of Interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords

  • Clostridium difficile
  • genomics
  • pediatrics
  • transmission
  • whole genome sequencing

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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