C. difficile Epidemic Still Poses Clinical Challenges

WASHINGTON — Rates of Clostridium difficile diarrhea have declined in Quebec since the 2003–2004 outbreak of a new highly transmissible and lethal strain, but infectious disease experts do not believe this means that the disease has peaked in North America.

“Personally, I'm a bit pessimistic. I think the property of this specific strain is such that it will persist for a long time,” Dr. Jacques Pepin of the University of Sherbrooke (Que.), said at a press briefing during the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Dr. Dale N. Gerding of Hines Veterans Affairs Hospital, Chicago, agrees. “Have we hit the peak of the epidemic yet? In the United States, I don't think we have.”

The strain is now present in all 50 U.S. states and is largely responsible for the changing epidemiology of C. difficile infection (CDI), noted Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, who first reported the appearance of the strain in six U.S. states in 2005 (N. Engl. J. Med. 2005;353:2433–41.

Recent studies suggest that the strain is present in 30%–50% of U.S. isolates, but the lack of national surveillance data makes it difficult to monitor. It is estimated that in 2006 more than 500,000 total CDI cases resulted—directly or indirectly—in more than 15,000 deaths. “There is marked geographic variation in rates of cases and deaths. It's [affected] by the age of the population,” Dr. McDonald said in a symposium held during the meeting.

Hospital survey data suggest that the rate of discharges with C. difficile listed as a diagnosis for short-stay patients rose from 30.7/100,000 population in 1996 to 77.3/100,000 in 2006, a slight decline from the 84.8/100,000 seen in 2005. National inpatient survey samples show a similar trend. There appears to be a slight leveling off, but it's far too soon to declare the epidemic over, Dr. McDonald said.

In a prospective study conducted at 12 Quebec hospitals, there were 1,703 CDI patients, with an incidence of 22.5 per 1,000 admissions and an 30-day attributable mortality rate of 6.9% (N. Engl. J. Med. 2005;353:2442–9).

The Quebec outbreak represented the first multihospital epidemic of a new strain of C. difficile. Since the peak years of 2003–2004, the incidence has yet to fall back to what it was before the outbreak. Before the strain arrived, death certificates listed about 100 deaths per year caused by C. difficile. That rose to about 700 deaths per year during the outbreak, and is now about 400. The population of Quebec is about 7 million, so an extrapolation to the United States would equal about 100,000 deaths, Dr. Pepin said.

“The new strain is not going to disappear. The proportion of cases caused by this strain has remained stable. It's possible to reduce the incidence, but I don't think we will ever get back to the incidence levels we had prior to that unless we have a vaccine,” he said.

The current treatments of choice for C. difficile—vancomycin and metronidazole—have been used for 30 years, Dr. Gerding noted. Recent data suggest that metronidazole does not work as well as it used to, particularly in severely ill patients. But concern about the disease has led to increased research into antimicrobial agents as well as unconventional approaches such as toxin binders, monoclonal antibodies, and “biotherapeutic” treatments such as fecal transfusions.

“It's a desperate situation and we need new treatment approaches,” he said.

Improvements in diagnostic testing will also be needed, said Dr. Lance R. Peterson, director of microbiology and infectious disease research at NorthShore University HealthSystem, Evanston, Ill., who also spoke at the symposium.

About 20% of all hospitalized patients have loose stools, most of which are not infected with C. difficile. Current enzyme immunoassays give rapid results, but their sensitivity is only about 70–80%, with a 3–5% false-positive rate. The error rates among the current tests have led to confusion in the literature regarding the epidemiology of the disease. The confusion includes controversy over whether proton pump inhibitors are related to C. difficile and whether some strains may not be related to antimicrobial use.

New molecular diagnostics include real-time polymerase chain reaction (PCR) tests, which can accurately detect 95%–98% of C. difficile infections within 2 hours. At least three companies are developing commercial versions of the test.

“We're starting to have a rapid test that's useful. … This will be imperative to understand the epidemiology of this changing emerging infection going forward,” said Dr. Peterson, who also is professor of pathology and medicine at Northwestern University, Chicago.

The new emphasis on prevention of health care-acquired infections could make a difference, Dr. McDonald noted. The CDC is working with hospitals to prevent outbreaks by revising antimicrobial prescribing practices as well as environmental efforts, such as using gowns and enforcing hand-washing rules. “Data suggest that many more cases of CDI can be prevented than we currently realize. … It seems like it's something that will require a new way of doing business with regard to infection-control measures.”

Dr. Pepin is on the advisory board for Acambis, which is developing a C. difficile vaccine. Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma Inc., and is a consultant for and/or holds research grants from several companies. Dr. Peterson has received research funding and/or consulting fees from several companies and the National Institutes of Health. Dr. McDonald reported having nothing to disclose.

WASHINGTON — Rates of Clostridium difficile diarrhea have declined in Quebec since the 2003–2004 outbreak of a new highly transmissible and lethal strain, but infectious disease experts do not believe this means that the disease has peaked in North America.

“Personally, I'm a bit pessimistic. I think the property of this specific strain is such that it will persist for a long time,” Dr. Jacques Pepin of the University of Sherbrooke (Que.), said at a press briefing during the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Dr. Dale N. Gerding of Hines Veterans Affairs Hospital, Chicago, agrees. “Have we hit the peak of the epidemic yet? In the United States, I don't think we have.”

The strain is now present in all 50 U.S. states and is largely responsible for the changing epidemiology of C. difficile infection (CDI), noted Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, who first reported the appearance of the strain in six U.S. states in 2005 (N. Engl. J. Med. 2005;353:2433–41.

Recent studies suggest that the strain is present in 30%–50% of U.S. isolates, but the lack of national surveillance data makes it difficult to monitor. It is estimated that in 2006 more than 500,000 total CDI cases resulted—directly or indirectly—in more than 15,000 deaths. “There is marked geographic variation in rates of cases and deaths. It's [affected] by the age of the population,” Dr. McDonald said in a symposium held during the meeting.

Hospital survey data suggest that the rate of discharges with C. difficile listed as a diagnosis for short-stay patients rose from 30.7/100,000 population in 1996 to 77.3/100,000 in 2006, a slight decline from the 84.8/100,000 seen in 2005. National inpatient survey samples show a similar trend. There appears to be a slight leveling off, but it's far too soon to declare the epidemic over, Dr. McDonald said.

In a prospective study conducted at 12 Quebec hospitals, there were 1,703 CDI patients, with an incidence of 22.5 per 1,000 admissions and an 30-day attributable mortality rate of 6.9% (N. Engl. J. Med. 2005;353:2442–9).

The Quebec outbreak represented the first multihospital epidemic of a new strain of C. difficile. Since the peak years of 2003–2004, the incidence has yet to fall back to what it was before the outbreak. Before the strain arrived, death certificates listed about 100 deaths per year caused by C. difficile. That rose to about 700 deaths per year during the outbreak, and is now about 400. The population of Quebec is about 7 million, so an extrapolation to the United States would equal about 100,000 deaths, Dr. Pepin said.

“The new strain is not going to disappear. The proportion of cases caused by this strain has remained stable. It's possible to reduce the incidence, but I don't think we will ever get back to the incidence levels we had prior to that unless we have a vaccine,” he said.

The current treatments of choice for C. difficile—vancomycin and metronidazole—have been used for 30 years, Dr. Gerding noted. Recent data suggest that metronidazole does not work as well as it used to, particularly in severely ill patients. But concern about the disease has led to increased research into antimicrobial agents as well as unconventional approaches such as toxin binders, monoclonal antibodies, and “biotherapeutic” treatments such as fecal transfusions.

“It's a desperate situation and we need new treatment approaches,” he said.

Improvements in diagnostic testing will also be needed, said Dr. Lance R. Peterson, director of microbiology and infectious disease research at NorthShore University HealthSystem, Evanston, Ill., who also spoke at the symposium.

About 20% of all hospitalized patients have loose stools, most of which are not infected with C. difficile. Current enzyme immunoassays give rapid results, but their sensitivity is only about 70–80%, with a 3–5% false-positive rate. The error rates among the current tests have led to confusion in the literature regarding the epidemiology of the disease. The confusion includes controversy over whether proton pump inhibitors are related to C. difficile and whether some strains may not be related to antimicrobial use.

New molecular diagnostics include real-time polymerase chain reaction (PCR) tests, which can accurately detect 95%–98% of C. difficile infections within 2 hours. At least three companies are developing commercial versions of the test.

“We're starting to have a rapid test that's useful. … This will be imperative to understand the epidemiology of this changing emerging infection going forward,” said Dr. Peterson, who also is professor of pathology and medicine at Northwestern University, Chicago.

The new emphasis on prevention of health care-acquired infections could make a difference, Dr. McDonald noted. The CDC is working with hospitals to prevent outbreaks by revising antimicrobial prescribing practices as well as environmental efforts, such as using gowns and enforcing hand-washing rules. “Data suggest that many more cases of CDI can be prevented than we currently realize. … It seems like it's something that will require a new way of doing business with regard to infection-control measures.”

Dr. Pepin is on the advisory board for Acambis, which is developing a C. difficile vaccine. Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma Inc., and is a consultant for and/or holds research grants from several companies. Dr. Peterson has received research funding and/or consulting fees from several companies and the National Institutes of Health. Dr. McDonald reported having nothing to disclose.

WASHINGTON — Rates of Clostridium difficile diarrhea have declined in Quebec since the 2003–2004 outbreak of a new highly transmissible and lethal strain, but infectious disease experts do not believe this means that the disease has peaked in North America.

“Personally, I'm a bit pessimistic. I think the property of this specific strain is such that it will persist for a long time,” Dr. Jacques Pepin of the University of Sherbrooke (Que.), said at a press briefing during the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

Dr. Dale N. Gerding of Hines Veterans Affairs Hospital, Chicago, agrees. “Have we hit the peak of the epidemic yet? In the United States, I don't think we have.”

The strain is now present in all 50 U.S. states and is largely responsible for the changing epidemiology of C. difficile infection (CDI), noted Dr. L. Clifford McDonald of the Centers for Disease Control and Prevention, who first reported the appearance of the strain in six U.S. states in 2005 (N. Engl. J. Med. 2005;353:2433–41.

Recent studies suggest that the strain is present in 30%–50% of U.S. isolates, but the lack of national surveillance data makes it difficult to monitor. It is estimated that in 2006 more than 500,000 total CDI cases resulted—directly or indirectly—in more than 15,000 deaths. “There is marked geographic variation in rates of cases and deaths. It's [affected] by the age of the population,” Dr. McDonald said in a symposium held during the meeting.

Hospital survey data suggest that the rate of discharges with C. difficile listed as a diagnosis for short-stay patients rose from 30.7/100,000 population in 1996 to 77.3/100,000 in 2006, a slight decline from the 84.8/100,000 seen in 2005. National inpatient survey samples show a similar trend. There appears to be a slight leveling off, but it's far too soon to declare the epidemic over, Dr. McDonald said.

In a prospective study conducted at 12 Quebec hospitals, there were 1,703 CDI patients, with an incidence of 22.5 per 1,000 admissions and an 30-day attributable mortality rate of 6.9% (N. Engl. J. Med. 2005;353:2442–9).

The Quebec outbreak represented the first multihospital epidemic of a new strain of C. difficile. Since the peak years of 2003–2004, the incidence has yet to fall back to what it was before the outbreak. Before the strain arrived, death certificates listed about 100 deaths per year caused by C. difficile. That rose to about 700 deaths per year during the outbreak, and is now about 400. The population of Quebec is about 7 million, so an extrapolation to the United States would equal about 100,000 deaths, Dr. Pepin said.

“The new strain is not going to disappear. The proportion of cases caused by this strain has remained stable. It's possible to reduce the incidence, but I don't think we will ever get back to the incidence levels we had prior to that unless we have a vaccine,” he said.

The current treatments of choice for C. difficile—vancomycin and metronidazole—have been used for 30 years, Dr. Gerding noted. Recent data suggest that metronidazole does not work as well as it used to, particularly in severely ill patients. But concern about the disease has led to increased research into antimicrobial agents as well as unconventional approaches such as toxin binders, monoclonal antibodies, and “biotherapeutic” treatments such as fecal transfusions.

“It's a desperate situation and we need new treatment approaches,” he said.

Improvements in diagnostic testing will also be needed, said Dr. Lance R. Peterson, director of microbiology and infectious disease research at NorthShore University HealthSystem, Evanston, Ill., who also spoke at the symposium.

About 20% of all hospitalized patients have loose stools, most of which are not infected with C. difficile. Current enzyme immunoassays give rapid results, but their sensitivity is only about 70–80%, with a 3–5% false-positive rate. The error rates among the current tests have led to confusion in the literature regarding the epidemiology of the disease. The confusion includes controversy over whether proton pump inhibitors are related to C. difficile and whether some strains may not be related to antimicrobial use.

New molecular diagnostics include real-time polymerase chain reaction (PCR) tests, which can accurately detect 95%–98% of C. difficile infections within 2 hours. At least three companies are developing commercial versions of the test.

“We're starting to have a rapid test that's useful. … This will be imperative to understand the epidemiology of this changing emerging infection going forward,” said Dr. Peterson, who also is professor of pathology and medicine at Northwestern University, Chicago.

The new emphasis on prevention of health care-acquired infections could make a difference, Dr. McDonald noted. The CDC is working with hospitals to prevent outbreaks by revising antimicrobial prescribing practices as well as environmental efforts, such as using gowns and enforcing hand-washing rules. “Data suggest that many more cases of CDI can be prevented than we currently realize. … It seems like it's something that will require a new way of doing business with regard to infection-control measures.”

Dr. Pepin is on the advisory board for Acambis, which is developing a C. difficile vaccine. Dr. Gerding holds patents for the treatment and prevention of CDI licensed to ViroPharma Inc., and is a consultant for and/or holds research grants from several companies. Dr. Peterson has received research funding and/or consulting fees from several companies and the National Institutes of Health. Dr. McDonald reported having nothing to disclose.