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 journalArticle

5 Citations (Scopus)

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

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Clostridium difficile
Clostridium Infections
Genome
Delivery of Health Care
Community Health Services
Nucleotides
Inpatients

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{46c9e281d645485981423c66dad5968e,
title = "Clostridium difficile whole genome sequencing reveals limited transmission among symptomatic children: A single-center analysis",
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.",
keywords = "Clostridium difficile, genomics, pediatrics, transmission, whole genome sequencing",
author = "Kociolek, {Larry K.} and Gerding, {Dale N.} and Espinosa, {Robyn O.} and Patel, {Sameer J.} and Shulman, {Stanford T.} and Ozer, {Egon A.}",
year = "2018",
month = "7",
day = "2",
doi = "10.1093/cid/ciy060",
language = "English (US)",
volume = "67",
pages = "229--234",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
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TY - JOUR

T1 - Clostridium difficile whole genome sequencing reveals limited transmission among symptomatic children

T2 - A single-center analysis

AU - Kociolek, Larry K.

AU - Gerding, Dale N.

AU - Espinosa, Robyn O.

AU - Patel, Sameer J.

AU - Shulman, Stanford T.

AU - Ozer, Egon A.

PY - 2018/7/2

Y1 - 2018/7/2

N2 - 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.

AB - 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.

KW - Clostridium difficile

KW - genomics

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KW - whole genome sequencing

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