The C. diff conundrum: Deadly new strain raises tough questions for ICPs

The C. diff conundrum: Deadly new strain raises tough questions for ICPs

An enormous problem . . . we are all going to be facing’

A highly virulent strain of Clostridium difficile (C. diff) continues to emerge in the United States and Canada, posing formidable challenges for infection control professionals because it can be deadly upon arrival and notoriously difficult to eradicate.

"If you have a program that simply says if you get a C. diff case put them in contact isolation and that will protect you, you are dreaming in technicolor," says Allison McGeer, MD, director of infection control at Mount Sinai and Princess Margaret Hospitals in Toronto. "It’s not true. It also is probably delusional — now that [the C. diff strain is geographically dispersed] — to think that most of the rest of us aren’t going to have to deal with it."

Researchers recently reported that isolates of the new C. diff strain have been collected from eight health care facilities in six states (Georgia, Illinois, Maine, New Jersey, Oregon, and Pennsylvania) in which outbreaks occurred between 2000 and 2003.¹ In addition, in the past two years, the Centers for Disease Control and Prevention (CDC) has received increased reports from health care facilities of cases of antibiotic-resistant, severe C. diff infections that have resulted in admissions to intensive care units, colectomies, and deaths.

"Some hospitals have had some good success controlling this strain; others have had limited success," says L. Clifford McDonald, MD, lead author of the research and medical epidemiologist in the division of health care quality promotion at the CDC. "Several hospitals have been grappling with it for well over a year, two years, and some even as long as five years. They have had moderate success. They’ve gotten rates down from their peak, but not back to their baseline."

Montreal ICPs still trying to douse fire

The same strain has wreaked havoc in Canada, causing a large regional outbreak in the Montreal area in the province of Quebec. The Canadian outbreaks have been marked by striking mortality rates, which apparently stem from a genetic mutation that spurs increased toxin production in the strain. A recent study of the outbreaks in Quebec found an attributable mortality rate of 6.9%, compared to rates ranging from 0.5% to 5.5% in previous studies of C. diff.² Having seen only one case of the outbreak strain get within her hospital walls, McGeer views the situation in Quebec province like a distant fire that may ride the wind her way.

"I think I had one death in my hospital last year due to C. diff and we’re not even really sure it was [the attributable cause]," she says. "These hospitals are talking about 40 deaths a year, and one was really pleased because they had only 10 deaths [in 2005]."

The situation in Canada certainly could be a cautionary tale for hospitals in the United States because it has taken a massive and costly effort to get infection rates back to within hailing distance of baseline.

"The Canadians have the best experience with this and they have reduced their rate by about half in the last year by applying increased infection control measures and really beefing up what they are doing," says C. diff researcher Dale Gerding, MD, associate chief of staff for research at the Hines VA Hospital and professor of medicine at Loyola University of Chicago. "They received a $20 million cash infusion from the province of Quebec to try and improve their infection control, and have brought their rates down from 22.5 [infections] to 12 per 1,000 discharges. But they started with a rate that was more like five [per 1,000 discharges] so they still have a ways to go."

The emergence of the pathogen raises difficult questions for antibiotic use, infection control and environmental eradication. Transmission occurs primarily in health care facilities, where exposure to antimicrobial drugs sets up the gut for onset of disease, triggering diarrhea that leads to a contaminated patient environment by the spore-forming anaerobic bacillus. "It is difficult," Gerding says. "There are problems getting the spores out of the environment and there are problems trying to keep health care workers using good hand hygiene. Compounding that is the use of antibiotics at such a high rate in the hospitalized population."

Indeed, prior administration of fluoroquinolones in particular seems to trigger the appearance of cases. Given that, the aforementioned research paper — co-authored by Gerding — raises the question of "whether a large-scale restriction of the use of these antimicrobial agents will be necessary to slow the geographic spread of the strain. . . . 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," the researchers warn.

However, such a restriction would be difficult and potentially counterproductive because fluoroquinolones are used for the treatment of many common infections. "That is something that no one has really tested," Gerding says. "Can you just eliminate a whole class of fluoroquinolone drugs if you are having an outbreak or epidemic, and by restricting them reduce the frequency of disease? Nobody has tested that hypothesis yet."

Cutting back antibiotics a trade-off?

Noting that hospitals in the Montreal area have cut back antibiotic use — with the exception of vancomycin — by some 25% to 35%, McGeer wonders if the effort against C. diff is exacting a cost in other patient infections. "I don’t think we know whether that [antibiotic] decrease is good for people or bad for people," she says. "I am concerned that there is a trade-off happening there. I know we use way more antibiotics than we need. There are two ways of looking at the 25% to 35% reduction: either it is not harmful to patients — in which case all of the rest of us ought to be on the band wagon; or it is harmful to patients and it is one more reason why we have an enormous problem with C. diff that we are all going to be facing."

Making the situation all the more confusing, there is some emerging evidence that some detergent bleach solutions may actually induce spore formation in C. diff, enabling it to persist in the environment even as you attempt to eradicate it, McGeer notes. "C. diff is just full of these kinds of conundrums," she says.

The situation is sufficiently troublesome that ICPs are left to take solace in a recent study by Gerding that finds alcohol hand rubs are not as ineffective as generally thought against C. diff. Traditional hand washing with soap and water still is the most effective weapon against transmission of C. diff, but many ICPs are just now getting health care workers to comply with the new emphasis on alcohol hand rubs between patients.

"I was actually somewhat reassured by that [study] because I can’t go back to soap and water," McGeer says. One reason is that sinks in some of her hospital rooms are located in patient bathrooms, meaning health care workers would have to enter a contaminated environment if they are treating a C. diff patient, she explains.

"Even if I achieved getting people to wash their hands — and I am having enough trouble getting them to use the alcohol hand wash — the adherence will be lower, and I am not sure that washing your hands in the patient’s bathroom is better than an alcohol hand wash," McGeer says. "So I am still very solidly in the alcohol hand wash camp. We’re not switching from alcohol hand washing between each patient. In the ideal world — if the environment is cleaned adequately — then soap and water is a better option, but I don’t live in the ideal world."

Contact isolation overwhelmed

Moreover, contact isolation did not work sufficiently to prevent the rise of the outbreak strain in the affected hospitals, and ICPs have had to go well beyond those measures in an attempt to eradicate it, she argues.

"I was recently talking to one of [the ICPs] in Quebec," she says. "When they get their third nosocomial C. diff infection in one unit in a month they close down the unit, remove the patients and [decontaminate it] before putting them in again. All of these hospitals were doing the [standard] recommendations for C. diff when this outbreak happened so clearly contact precautions don’t work."

The most recent take on infection control measures comes in McDonald and Gerding’s paper, which recommends "strict infection-control measures, including contact precautions" that include:

• placing the patient in a private room or with another patient with C. diff-associated disease;
• requiring health care workers wear gloves and gowns when entering the room;
• patient care equipment (such as blood-pressure cuffs and stethoscopes) either is used only for the patient or is cleaned before it is used for another patient;
• enhanced environmental cleaning with diluted bleach should be used to eliminate C. diff spores.
• Because alcohol is ineffective in killing C. difficile spores, it is prudent for health care workers to wash their hands with soap and water, rather than with alcohol-based waterless hand sanitizers, when caring for patients with C. diff-associated disease during an outbreak.

Need for enhanced surveillance

Knowing that case detection is critical, public health officials and their clinical partners are urging inpatient health care facilities in North America to track the incidence of C. diff-associated disease. Clinical outcomes of infected patients also should be monitored, especially if an increase in rates is noted.

"We really want everyone to have their guard up and doing surveillance," McDonald says. "We are not proposing a large national surveillance system. I don’t think there is that consensus out there, but we are saying that every hospital should be looking at their own rates. We would like everyone to be at least counting the number of positive tests that are coming though their lab to make sure they are not seeing an increase."

The recommendation comes in the aforementioned research paper, which has a CDC lead author but not the formal weight of an official guideline by the agency. But clearly concern is mounting, as evidenced by recent publication of some relatively incomplete data on the possible emergence of C. diff in the community. While investigations are ongoing, some of the cases have a disturbing feature: acquisition of C. diff without prior exposure to antibiotics. "Those are the ones that really have to be looked at carefully — that would be virtually unheard of," Gerding says.

Given the changing epidemiology of the pathogen in both the clinical setting and the community, there have been discussions of making C. diff a nationally reportable infection.

"We don’t have a national C. diff surveillance plan," McDonald says. "There has been discussion, should something like C. diff be nationally reportable? I hear the question raised. We’re not there yet to make such recommendations."

In the interim, enhanced surveillance by individual ICPs may cast light on the scale of the problem. A recently published editorial in the New England Journal of Medicine stresses 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. Standard stool assays available in most laboratories will not identify this epidemic strain, but the strain might be suspected on the basis of the number and severity of cases."³

Initial detection and prevention certainly beats the alternative. The strain can be a persistent nemesis once established within hospital walls. "If you really pay attention to C. diff like these hospitals in Montreal have been doing, you can get the rate down by 50% to 70%," McGeer says. "The important question that is left is how to go from 50% to 70% to 90%. [The situation] is much better, but it is still twice what they had before and four times what is happening in other hospitals. And that is after a huge, unbelievable amount of effort with people working really hard."

An apt infectious disease analogy may be severe acute respiratory syndrome (SARS), which caused only minor problems at some hospitals and overwhelmed others. "Undoubtedly there are hospitals that have had this strain and not had a lot of trouble with it," McGeer says. "There were a few places that got SARS patients that did OK and there were a few that got one [case] that blew the lid off."

References

1. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Eng J Med2005; 353:2,433-2,441.
2. Loo VG, Poirier L, Miller M, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Eng J Med 2005; 353:2,442-2,449.
3. Bartlett JG, Perl TM. The new Clostridium difficile — What does it mean? Editorial. N Eng J Med 2005; 353:2,503-2,505.