C diff NAP1 Strain Associated With Symptomatic Infection

Emma Hitt, PhD

November 02, 2011

November 2, 2011 — Patients with symptomatic healthcare-associated Clostridium difficile infection are more likely to be infected with the North American pulsed-field gel electrophoresis type 1 (NAP1) strain and are more likely to be older than asymptomatic patients who are only colonized with the bacterium, according to new research.

Vivian G. Loo, MD, from the McGill University Health Centre in Montreal, Quebec, Canada, and colleagues reported their findings in the November 3 issue of the New England Journal of Medicine.

According to the researchers: "After exposure to C. difficile, some patients remain asymptomatic, whereas others have illness ranging from mild diarrhea to fulminant colitis." They add that "[v]ariability in host factors may explain the wide spectrum of symptoms and course."

The study sought to examine the relationships among host risk factors, bacterial virulence, and host immunity in healthcare-associated C difficile infection vs asymptomatic colonization.

Dr. Loo and colleagues collected demographic and other information and weekly stool samples or rectal swabs from 4143 patients in 6 hospitals throughout Quebec and Ontario, Canada.

The genotypes of C difficile isolates were determined with pulsed-field gel electrophoresis, and levels of serum antibodies against C difficile toxins A and B were assessed.

Of the patients, 2.8% had C difficile infection, and 3.0% were only colonized with the bacteria. The researchers found that patients who were older and who used antibiotics or proton-pump inhibitors had a significantly increased risk for infection.

In their multivariate analysis the investigators adjusted for age, sex, Charlson comorbidity index, previous hospitalization, serologic data, and medication use in the 8 weeks before hospitalization, infection, or colonization.

For every additional year of age after age 18 years, the adjusted risk for healthcare-associated C difficile infection increases by approximately 2%. Patients receiving antibiotics had about a 5-fold increased risk for infection vs colonization, and patients receiving proton pump inhibitors had a 2.64-fold risk of being infected vs a 1.71-fold risk of being colonized compared with those not using proton-pump inhibitors.

In addition, colonization was more likely if a patient was hospitalized in the previous 2 months; used chemotherapy, proton-pump inhibitors, or H2 blockers; and had antibodies against toxin B.

The NAP1 strain was predominant among patients with C difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. "Among patients with health care–associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the [NAP1] strain," the authors note.

"[O]ur study shows differential effects of age, medication use, and host immunity and pathogen variables on health care–associated C. difficile infection and health care–associated C. difficile colonization," the authors conclude. "The findings add to the understanding of C. difficile infection and colonization and have implications for prevention and therapy," they suggest.

The study was not commercially supported. Dr. Loo reports receiving consulting fees from Merck.

N Engl J Med. 2011;365:1693-1703. Abstract