New epidemic strain of C. difficile seen emerging in North America

Two reports highlight the emergence of a new, highly toxic strain of Clostridium difficile that is resistant to fluoroquinolones and is causing geographically dispersed outbreaks. The reports were released early by the New England Journal of Medicine to coincide with this week's paper in the Morbidity and Mortality Weekly Report describing C. difficile infections in low-risk patients. The Centers for Disease Control and Prevention has received an increased number of reports from health care facilities of cases of severe C. difficile-associated disease, according to one of the NEJM papers. Dr. L. Clifford McDonald, from the CDC in Atlanta, and colleagues say this suggests the emergence of an epidemic strain with either increased virulence or antimicrobial resistance or both. To test this hypothesis, the research team collected 187 C. difficile isolates from outbreaks since 2001 in eight health care facilities in six states, and compared their characteristics with those of 6000 historical isolates obtained between 1984 and 1990. One strain, comprising 51% of recent isolates, was identified by restriction-endonuclease analysis as belonging to group BI, and by pulsed-field gel electrophoresis as belonging to NAP1. Isolates of this strain were positive for binary toxin, and contained an 18-base pair deletion in the toxin A and B repressor gene tcdC. In contrast, only 14 cases from the historic database belonged to BI/NAP1 type. All of the current BI/NAP1 isolates, and none of the historic isolates, were resistant to gatifloxacin and moxifloxacin. "If this epidemic strain continues to spread and to contribute to increased morbidity and mortality, it will be important either to reconsider the use of fluoroquinolones or to develop other innovative measures for controlling C. difficile-associated disease," Dr. McDonald's group writes. They stress the need for strict infection-control measures. Because alcohol does not kill C. difficile spores, they recommend that health care workers wash their hands with soap and water instead of using alcohol-based waterless hand sanitizers during outbreaks. According to a second report in the Journal, Canadian researchers, led by Dr. Vivian G. Loo from McGill University Health Center in Montreal, identified 1719 episodes of C. difficile-associated diarrhea at 12 Quebec hospitals between January and June of 2004. The incidence was 22.5 per 1000 admissions, up from a mean incidence of 6 per 1000 admissions at 18 Canadian institutions in 1997. The 30-day attributable mortality rate was 6.9% -- compared with 1.5% in 1997 -- ranging from 1.6% for patients less than 40 years old to 14.0% for those over age 90. The predominant strain was similar to that observed by Dr. McDonald's group. Characterization of 157 isolates showed that the binary toxin genes and partial deletions in the tcdC gene were present in 84.1%. The predominant strain was resistant to ciprofloxacin, moxifloxacin, gatifloxacin, and levofloxacin. Dr. Loo's team conducted a case-control study comparing 237 cases with 237 controls. Independent risk factors for C. difficile-associated diarrhea included exposure to cephalosporins (odds ratio 3.8) and fluoroquinolones (odds ratio 3.9). In an editorial accompanying the two papers, Drs. John G. Bartlett and Trish M. Perl, from Johns Hopkins University School of Medicine in Baltimore, point out that standard stool assays will not identify this epidemic strain. They therefore advise that "physicians and infection-control personnel need to monitor for an increasing incidence of C. difficile-associated disease on the basis of some classic features: the administration of antibiotics complicated by diarrhea, fever, leukocytosis, sometimes with a leukemoid reaction, and hypoalbuminemia or toxic megacolon, or both." They agree with both research teams that "antibiotic stewardship with restraint in the use of epidemiologically implicated antimicrobial agents" is required to control the epidemics. N Engl J Med 2005;353:2433-2449,2503-2505.
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