SHEA Conference: C. difficile toxic strain emerges in U.S., Canada

SHEA Conference

C. difficile toxic strain emerges in U.S., Canada

More toxin production may spur transmission

A new virulent strain of Clostridium difficile rapidly continues to emerge in both the United States and Canada, infectious disease physicians reported recently in Los Angeles at the annual meeting of the Society for Healthcare Epidemiology of America (SHEA).

C. diff is a common cause of diarrhea in hospitalized patients following antibiotic therapy. However, the new strain is highly toxic and can cause severe diarrhea, colitis, surgical removal of the colon, or even death.

"C. difficile-associated diarrhea is nearly always linked to the use of antibiotics, prescribed for unrelated conditions," said L. Clifford McDonald, MD, medical epidemiologist in the division of healthcare quality promotion at the Centers for Disease Control and Prevention. "Antibiotics upset the natural balance of the colon, killing off many normally occurring bacteria and allowing C. difficile to flourish."

In one presentation at SHEA, scientists working with the CDC found that a strain of C. difficile responsible for an outbreak at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) in Quebec, Canada, produces much higher levels of toxins A and B than other strains of the bacteria.

"Toxins A and B are the cause of C. difficile-associated diarrhea and other symptoms," said Michel Warny, MD, PhD, director of bacterial process development at Acambis Inc. in Cambridge, MA. "The ability of this emerging strain to produce high levels of toxins A and B in the laboratory may explain its virulence in patients."

At CHUS, incidence of C. difficile-associated diarrhea has quadrupled from 1991 to 2003, and the case-fatality rate has more than doubled.

"Quebec has experienced over the last two to three years a very severe hospital-based epidemic of C. difficile," Warny said.

"There has been an overall increase in cases and a higher mortality rate with the new strains. The same isolate was reported by CDC last year in various states in the United States," he added.

Warny and colleagues tried to determine the molecular characteristics of C. diff isolates responsible for the outbreak at CHUS and assess the levels of toxin A & B production. They used pulsed-field gel electrophoresis (PFGE) and determined toxin A & B and accessory genes by toxinotyping. A single PFGE type, toxinotype III, was identified in 82% of isolates from CHUS. The strain was identical to the strain responsible for several geographically dispersed North American outbreaks. Both the level and pattern of toxin production in the epidemic strain is consistent with "defective tcdC regulation," enabling rapid and strong toxin production that may overcome immune defenses, Warny said. Future studies need to confirm whether increased toxin production is responsible for more severe disease and enhanced transmissibility.

"We are very interested in the epidemiology of these organisms," Warny said. "Does it have the ability to produce more toxins? We don’t know. [But] it is possible that a strain that makes more toxins is more contagious."

Complicating matters, the new strain of the bacteria is resistant to fluoroquinolines. According to data from two surveys conducted in 2004 that were presented at the SHEA meeting, 38% of infectious disease experts reported an increase in the frequency of C. difficile-related disease and 39% reported an increase in severity. Collectively, the 201 survey respondents who perceived an increase in cases of C. difficile reported an estimated 3,292 cases. Among these were 435 patients with toxic megacolon, a dangerous expanse of the colon; 181 of these patients required surgical removal of their colons, and 198 patients died of complications.