976. Clostridium difficile colonization molecular epidemiology and anti-toxin serological responses in healthy infants: A prospective cohort study
Session: Oral Abstract Session: Healthcare Epidemiology: The Poop Pager and Other Novel Perspectives on C. difficile in the Healthcare Setting
Friday, October 5, 2018: 11:30 AM
Room: S 156

Background:

Infant C. difficile colonization is common, but the molecular epidemiology and immunologic consequences of colonization are poorly understood.

Methods:

In this prospective cohort study of healthy infants, serial stools collected between 1-2m and 9-12m old were tested for glutamate dehydrogenase (detects non-toxigenic or toxigenic C. difficile [TCD]), tcdB PCR (detects TCD), and cultured for C. difficile. Isolates underwent whole genome sequencing and multilocus sequence typing (MLST). Clonal strains were identified by single nucleotide variant (SNV) analysis. TCD was confirmed by BLAST identification of tcdA/tcdB. Serum collected at 9-12m old underwent ELISA for measurement of IgA, IgG, and IgM against TCD toxins A and B. For comparison, anti-toxin IgG was measured in cord blood of 50 consecutive full-term deliveries (unrelated to study infants). Arbitrary ELISA units were compared by Wilcoxon rank-sum.

Results:

Among 32 infants, 16 (50%) had at least one TCD+ stool, 12 of whom were colonized at least 1m prior to serology measurements (Figs. 1 and 2). A variety of STs were identified, and evidence of putative in-home (enrolled siblings) and outpatient clinic transmission was identified (Fig. 3). Infants with TCD colonization had significantly greater levels of anti-toxin IgA and IgG compared to non-colonized infants and IgG compared to unrelated cord blood (Table 1).

Conclusion:

Infant C. difficile colonization is a dynamic process with variable strain types and duration. Outpatient clinics may be a C. difficile reservoir for some patients. TCD colonization is associated with a humoral immune response against toxins A and B, but whether natural TCD immunization protects against CDI later in life requires further investigation.

Table 1: Anti-toxin serology (arbitrary ELISA units)

Group

Tox A IgA

Tox A IgG

Tox A IgM

Tox B IgA

Tox B IgG

Tox B IgM

Not colonized with TCD (n=16)

1.37

10.14

2.74

0.8

6.50

6.14

Colonized with TCD for at least 1 month (n=12)

4.23*

37.87*

2.54

1.73*

20.76*

5.96

Cord Blood (n=50)

10.81^

8.34^

*P<0.05 (colonized vs. non-colonized); ^P<0.05 (colonized vs. cord blood)


Fig. 1: Infant classification


Fig. 2: Chronology and results of infant stool C. difficile testing


Fig. 3: Molecular epidemiology of infant C. difficile isolates

Larry Kociolek, MD, MSCI1, Ciaran P. Kelly, MD2, Robyn Espinosa, MPH3, Maria Budz, MT3, Aakash Balaji, BS4, Egon Ozer, MD, PhD4, Robert Tanz, MD5, Xinhua Chen, PhD2 and Dale N Gerding, MD, FIDSA6, (1)Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, (2)Beth Israel Deaconess Medical Center, Boston, MA, (3)Ann & Robert H. Lurie Children's Hospital of Chica, Chicago, IL, (4)Northwestern University Feinberg School of Medicine, Chicago, IL, (5)Children's Memorial Hospital, Chicago, IL, (6)Loyola University, Hines, IL

Disclosures:

L. Kociolek, Alere/Techlab: Investigator , Research support .

C. P. Kelly, Actelion: Consultant , Consulting fee . Artugen: Consultant , Consulting fee . Facile: Consultant , Consulting fee . GSK: Consultant , Consulting fee . MSD: Consultant , Consulting fee . Seres: Consultant , Consulting fee . Summit: Consultant , Consulting fee . Vedanta: Consultant , Consulting fee .

R. Espinosa, None

M. Budz, None

A. Balaji, None

E. Ozer, None

R. Tanz, None

X. Chen, None

D. N. Gerding, Merck: Scientific Advisor , Consulting fee . Actelion: Scientific Advisor , Consulting fee . DaVolterra: Scientific Advisor , Consulting fee . Summit: Scientific Advisor , Consulting fee . Rebiotix: Medical Officer and Scientific Advisor , Consulting fee . Pfizer: Consultant , Consulting fee . MGB Pharma: Consultant , Consulting fee . Sanofi Pasteur: Consultant , Consulting fee . Seres: Investigator , Research grant . CDC: Investigator , Research grant . US Dept VA: Investigator , Research grant . Treatment/Prevention of C. difficile: Patent Holder , no license or royalties .

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