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177 Impact of North American Pulsed-field Type 1 (NAP1) Clostridium difficile Strain on Disease Severity and Outcome

Saturday, April 2, 2011
Trinity Ballroom (Hilton Anatole)
Jessica Cohen, MPH , Centers for Disease Control and Prevention, Atlanta, GA
Duncan R. MacCannell, PhD , Centers for Disease Control and Prevention, Atlanta, GA
Stacy M. Holzbauer, DVM , CDC CEFO assigned to the MN Dept. of Hlth, St. Paul, MN
Kelly R. Kast, MSPH , Colorado Department of Health, Denver, CO
Ghinwa Dumyati, MD , University of Rochester, Rochester, NY
Lisa Winston, MD , UCSF Department of Medicine, San Francisco, CA
Michelle Whitbread , CT Emerging Infections Program, New Haven, CT
L. Clifford McDonald, MD , Centers for Disease Control and Prevention, Atlanta, GA
Fernanda C. Lessa, MD, MPH , Centers for Disease Control and Prevention, Atlanta, GA
Background:

Although increases in the incidence and severity of C.difficile infection (CDI) are often attributed to the emergence of the North American pulsed-field type 1 (NAP1) strain, the impact of NAP1 on disease severity and outcomes, particularly in non-outbreak settings, remains unclear.

Objective:

To evaluate the association of the NAP1 strain with severe disease and outcome.

Methods:

Data obtained between January and September 2010 from the CDC’s Emerging Infections Program (EIP) population-based CDI surveillance in select counties across 8 U.S. states were analyzed. A CDI case was defined as a positive C.difficile toxin assay in a surveillance area resident ≥1 years-old with no positive toxin assay in the preceding 8 weeks. For each CDI case identified, a standardized case report form was abstracted from patient records by trained EIP staff. CDI cases were classified as healthcare-associated if specimens were collected > 3 calendar days after hospital admission, in long term care-facilities, or within 3 days after admission, but in a patient with prior healthcare exposure ( (i.e. hospitalization or long-term care facility residency in prior 12 weeks). A convenience sample of stool specimens linked to case data was submitted to reference laboratories for culture and molecular characterization. Severe disease was defined as leukocytosis (>15,000/µL) and/or toxic megacolon or ileus; severe outcome included in-hospital mortality, ICU admission within 7 days after diagnosis, and/or colectomy related to CDI. Univariate and multivariate analyses were performed using stepwise logistic regression to identify independent predictors of severe disease and severe outcome.

Results:

A total of 322 C.difficile isolates linked to CDI case data were available from 5 of the 8 EIP sites. Of these, 89 (28%) were NAP1. CDI case-patients with the NAP1 strain were more likely than those with a non-NAP1 strain to be non-white (34% vs. 22%; P=0.04) and to have resided in a long-term care facility in the 12 weeks before infection (21% vs. 11%; P=0.02). NAP1 case-patients did not differ significantly from non-NAP1 case-patients in terms of sex, Charlson index, or association with healthcare. Of the 322 CDI case-patients, 42 (13%) developed severe disease and 17 (5%) had severe outcome. In multivariate analysis, independent predictors of severe C. difficile disease included: age > 65 years (aOR=2.3; P=0.004), white race (aOR=3.74; P=0.01) and infection with NAP1 (aOR=2.27; P=0.02); whereas only the Charlson index (OR=1.37; P=0.0014) was significantly associated with severe outcome.

Conclusions:

In a large cohort of CDI cases identified in non-outbreak settings across 5 geographically diverse areas, infection with a NAP1 strain was significantly associated with severe disease but not with severe outcome. Evaluating these associations across more surveillance sites will be critical to confirm these findings.