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

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.


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


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.


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.


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.