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Further Insights into Worsening Clostridium difficile Disease

Two studies indicate widespread dissemination of a fluoroquinolone-resistant C. difficile strain with increased virulence.

Recently, numerous investigators have reported an increase in the frequency and severity of Clostridium difficile disease in institutions in the U.S. and Canada (see, for example, Journal Watch Infectious Diseases May 6 2005 and Oct 21 2005). Two new reports provide evidence linking this change in epidemiology to the dispersal within North America of a new, highly virulent strain of the organism.

McDonald and colleagues obtained 187 C. difficile isolates from eight U.S. healthcare facilities, in six states, where outbreaks had occurred since 2001. Molecular typing showed that one strain (BI/NAP1) was present in patients at all eight facilities and accounted for 50% of the isolates at five of the eight institutions. Further analyses indicated that all the isolates of this strain were highly related, had a similar combination of toxin A and B genes, contained a third binary toxin, and had a deletion in a regulatory gene that appears to limit toxin A and B production. Antibiotic-susceptibility testing of 24 B1/NAP1 isolates revealed that 19 were resistant to clindamycin and all were resistant to levofloxacin, gatifloxacin, and moxifloxacin.

Loo and colleagues undertook a prospective analysis of all cases of nosocomial C. difficile disease that occurred at 12 hospitals in Quebec, Canada, from January through June 2004. They identified 1719 episodes in 1703 patients (mean overall incidence, 22.5 cases per 1000 admissions). Among 422 patients who died 30 days after diagnosis of C. difficile disease, C. difficile infection was the attributable cause of death in 117 and a contributing factor in an additional 127. Recent use of either a cephalosporin or a fluoroquinolone (but not of other antibiotics) was significantly associated with C. difficile disease. Molecular and antibiotic susceptibility studies were performed on 157 available C. difficile isolates, and 132 shared the characteristics noted in the predominant clone in McDonald and colleagues’ study. Severe disease (defined as death within 30 days, or illness requiring intensive care or colectomy) was seen in 22 of the 132 patients infected with this strain, but in none of the 25 patients infected with other strains (P=0.03).

Comment: These complementary studies provide clear evidence that a more virulent, antibiotic-resistant C. difficile strain has emerged and has been disseminated within the U.S. and Canada. As noted in an accompanying editorial, institutions must monitor more carefully for C. difficile disease and, if increases are noted, should aggressively initiate both infection-control and antibiotic-stewardship policies.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases December 21, 2005

Citation(s):

McDonald LC et al. An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med 2005 Dec 8; 353:2433-41.

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• Medline abstract (Free)

Loo VG et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile–associated diarrhea with high morbidity and mortality. N Engl J Med 2005 Dec 8; 353:2442-9.

• Original article (Subscription may be required)
• Medline abstract (Free)

Bartlett JG and Perl TM. The new Clostridium difficile — What does it mean? N Engl J Med 2005 Dec 8; 353:2503-5.

• Original article (Subscription may be required)
• Medline abstract (Free)