March 12, 2012

Combating Clostridium Difficile
By Jessica Girdwain
For The Record
Vol. 24 No. 5 P. 24

Patients of advanced age with antibiotic exposure, GI surgery, long institutional stays, or serious underlying illness are at increased risk of acquiring this bacterial infection.

Clostridium difficile (C diff) is a disease that causes severe diarrhea and primarily threatens older patients in hospitals and elder care facilities. To call it a thorn in the side of healthcare workers would be an understatement. The virulent bacterial infection is quick to spread and difficult to remove from hospital environments, and its incidence has exploded in the last decade. In fact, according to the Centers for Disease Control and Prevention (CDC), it has caused more deaths in the United States than all other intestinal infections combined.

While those infected are often only mildly sick, C diff can advance to a point where it “irreversibly damages the colon,” says William A. Petri, Jr, MD, PhD, a professor of internal medicine and pathology and the associate director of microbiology at the School of Medicine at the University of Virginia. In severe cases, C diff may cause sepsis, multiorgan failure, intestinal perforation, or death.

It’s a disease that traditionally affects adults over the age of 65, perhaps due to their weakened immune systems. “What’s at least a possibility is that they don’t develop a good immune response to the C diff toxins so they’re more prone to get infected in the first place. Add to that the fact that they can’t develop a good immune response, and they’re more likely to experience a recurrence of the infection,” says Stuart Cohen, MD, coauthor of “Clinical Practice Guidelines for Clostridium difficile Infection in Adults” published in the May 2010 issue of Infection Control & Hospital Epidemiology.

Additionally, older adults are more likely to suffer from other medical illnesses, such as heart disease and emphysema, so once they get an infection like C diff, it’s more likely to become severe, and “an elderly person doesn’t respond as well to aggressive infections, making outcomes worse,” says Cohen.

The origin of C diff infection (CDI) may not always point to antibiotics as the culprit, according to recent research. Results of the study “Predictors of Hospitalization in Community-Acquired Clostridium difficile Infection,” presented in October at the American College of Gastroenterology’s annual scientific meeting, notes that other undefined causes of the infection may exist and could predict a patient’s likelihood of requiring hospitalization.

Another study conducted by Winthrop-University Hospital in Mineola, New York, “An ‘On-Admission’ Prediction Model of Disease Severity in Clostridium difficile Infection,” suggests that clinicians pay particular attention to patients at the time of CDI diagnosis because the nursing home residence factor apparently serves as a significant predictor of outcomes.

In addition to the confined living quarters and daily group activities among nursing home residents, this population is more likely to be taking antibiotics, increasing the likelihood of contracting a more severe strain of the disease, according to researchers.

Skyrocketing Rates
The veritable explosion of CDI is staggering: Between 1996 and 2009, C diff rates for hospitalized people over the age of 65 increased 200%, according to the latest data from the CDC. As age increased, so did the risk of infection.

Several theories have emerged to explain what’s responsible for the huge increase. One is the overuse of antibiotics, including fluoroquinolones. “C diff flourishes where other bacteria get killed, so antibiotics we use on infections, like community-acquired pneumonia, kill normal gut flora. C diff comes in and is then able to grow like crab grass,” says Rebekah Moehring, MD, an infectious disease fellow at Duke University School of Medicine in Durham, North Carolina.

“The biggest risk factor for your patients acquiring C diff is antibiotic use—and judicious use is critical. One thing I often hear about in long-term elder care facilities is that when a resident’s urine looks cloudy, the first thing that happens is a doctor prescribes antibiotics before evaluating if it’s truly an infection,” Cohen says. He notes that the prudent use of antibiotics is something physicians should be aware of in efforts to control C diff rates. Such efforts are among the reasons many hospitals are instituting antibiotic stewardship programs led by infectious disease physicians to help doctors more appropriately use antibiotics.

Another factor responsible for the increase is a new strain of the bacteria that has rapidly emerged in the last decade, as noted by the CDC. In 2004, NAP1 was discovered and linked to several hospital outbreaks. Known to be more virulent than other strains, it produces more exotoxins along with an additional toxin called a binary toxin. “This new strain produces 10 times the toxins than previous strains,” says Petri. When it causes sickness, these cases are more severe, creating a greater number of complications, according to Petri.

 Treatment of this strain is often more difficult because it is resistant to fluoroquinolones, says Moehring.

She says more CDI cases are being reported simply because doctors are aware of the condition and looking for it. The increased awareness, which is good, increases the likelihood that doctors will properly identify the symptoms and quickly test and confirm the diagnosis.

“We also think that improved testing identifies more cases, and this may also contribute to the increase in C diff,” notes Moehring.

An Ounce of Prevention 
Preventing CDI is often more basic than healthcare workers might imagine, and many effective procedures stem from logical solutions. “We have precautions set in place because they make sense, though no studies tell us how helpful they are. The research in prevention of C diff is, unfortunately, just not very good,” says John Bartlett, MD, a professor of medicine and infectious diseases at Johns Hopkins University in Baltimore. Regardless, the following are wise precautionary steps to take:

• Healthcare providers should wear gowns and gloves to create a barrier between the worker and the environment and prevent transmission from practitioners to other patients via hands or other body parts.

• Promptly identify patients with C diff. Patients will exhibit clinical symptoms (watery diarrhea, fever, nausea, abdominal pain or tenderness, loss of appetite) and test positive for the C diff organism or its toxin.

• Place patients with C diff in private rooms or isolate them with other patients with C diff infections. However, “The time needed to keep the patients separated hasn’t been definitively answered. It’s important to know that even when the patient is starting to feel better, we can still detect C diff in stools,” says Moehring. It’s best to wait until a patient is discharged from the hospital or, in the event a patient is spending an extended time period in the hospital, doctors should wait until he or she has completed treatment and is symptom free, although “it’s a different situation for every patient,” Moehring says.

• Wash hands with soap and water before and after interacting with each patient. Avoid alcohol-based solutions, as these don’t readily kill C diff spores.

• Disinfect hospital rooms properly. As a spore-forming organism, C diff can remain on surfaces, such as bed rails or counters, for an extended period of time. “It doesn’t die and just sits there for days and days,” says Moehring. These spores are also resistant to a lot of antiseptics and hospital-grade disinfectants, making them a challenge to remove. The solution: Bleach is best, Moehring says. (Researchers are working to develop a better way to clean hospital rooms. For example, Duke University School of Medicine is set to begin testing on a promising new way to disinfect rooms using an ultraviolet light device.)

CDI Diagnosis
Bartlett says if a patient tests positive for CDI, the most important thing for physicians to do is carefully scrutinize the test they’re using. “There’s a fair amount of new testing that’s pretty complicated, and you have to know what type of results you’re looking at,” he says. Because these tests are different in terms of what results they show and their sensitivity, doctors must be in tune with the laboratory to be able to analyze the results accurately. One such test that’s appeared in the last five years, called polymerase chain reaction (PCR), identifies actual DNA from C diff vs. looking for toxins in a stool test. It’s more sensitive, making it less likely to turn up a false-negative.

Of the 40 hospitals affiliated with the Duke Infection Control Outreach Network, about seven or eight use PCR testing, says Moehring. “While it takes more lab expertise, it does perform better, and I suspect more facilities will start to move toward using it,” she says.

Before testing even begins, Cohen says doctors should be on alert for patients who are highly suspect for contracting the infection. “If an older patient is seriously ill with diarrhea, you have to treat them before you receive the results. The sooner you do that, the more likely you’ll get a good outcome,” he says. Additionally, many patients show an atypical presentation of CDI. In some, Cohen notes, they may have an ileus. “Many times, doctors should consider C diff even if their patient does not get diarrhea.”

Treatment Options
Most patients with CDI can be successfully treated with antibiotics; metronidazole, or vancomycin, is commonly prescribed. A new antibiotic called fidaxomicin has recently been approved by the FDA to treat CDI. One piece of information to note about the drug, Petri says, is that it offers lower rates of relapse (which are typically around 10% to 20%), though this claim is not yet FDA approved.

A 2011 study published in The New England Journal of Medicine compared fidaxomicin with vancomycin. Patients received 200 mg of fidaxomicin or 125 mg of vanomycin orally for 10 days. While both antibiotics cured patients with equal efficacy, those on fidaxomicin experienced a significantly lower recurrence rate (15.4%) than those on vanomycin (25.3%).

Although fidaxomicin is certainly promising, Moehring doesn’t expect the drug to take over as the primary form of treatment any time soon. “It’s very expensive right now. Since the research has shown that it’s equivalent in terms of efficacy in the first occurrence, it might make a good choice for patients with recurring infections,” she says. “We’ll need to see more data, and they’ll have to make it more practical to use in terms of price in order to see widespread use.”

While antibiotics may be a first-line treatment, many CDI cases are recurring and may require additional procedures. One such option, fecal transplant, takes stool from a healthy donor and replaces the colon’s contents in patients with C diff. However, the procedure is appropriate primarily for treating relapse. “About 250 cases have been reported, and the procedure is almost universally successful,” notes Bartlett. It’s an important procedure with which physicians should become familiar because patients often come into the office asking about these transplants after doing Internet research, he says.

Recent studies presented at the American College of Gastroenterology’s annual meeting attest to fecal transplant’s effectiveness. One study conducted at the Digestive Health Center at Integris Baptist Medical Center in Oklahoma City found that symptoms of C diff were resolved in 98% of patients who underwent the procedure.

But doctors should make patients aware that a fecal transplant is appropriate only when the standard method for treating relapse fails, he notes. The number of clinicians performing the procedure is limited so Bartlett recommends healthcare practitioners know where in their area it’s available.

A new surgical procedure is bringing hope to the 10% of severely sick patients who, because of CDI, require a total colectomy. In a recent study published in Annals of Surgery, the authors performed an ileostomy in 42 patients and compared the results with 42 patients who had previously undergone a colectomy. Of the ileostomy group, eight patients died compared with 21 in the colectomy group. Though researchers say that randomized trials are needed to confirm their results, Bartlett says the surgery is an exciting advancement. “The good news about the procedure is that it allows patients to keep their colon,” he says.

The Future for CDI
A vaccine to prevent C diff has already reached phase 2/early phase 3 trials. The vaccine would be appropriate only for at-risk patients, namely elders who are hospitalized and taking antibiotics, according to Bartlett. In the future, patients who have an anticipated hospital stay, such as for elective surgery, and who will be exposed to antibiotics will become good candidates for the vaccine. Also, patients who are immunosuppressed but still respond to vaccines may consider it, too. “We’re still awaiting results on the vaccine but do know that it will be effective,” says Bartlett.

Regardless, experts continue to advance the field to prevent future hospital outbreaks. “The series of new drugs and strategies coming down the pipeline are set to change the whole field of C diff in five years,” says Cohen.

One area on which infectious disease specialists are keeping a close eye is the transfer of CDI into the community. “People are getting C diff who had no exposure to healthcare facilities or hospitals. It’s concerning for everyone because the infection is getting out,” says Moehring. In addition, doctors remain unaware of how it is traveling into the community, though future research will determine where it’s coming from and how to contain this dangerous infection.

— Jessica Girdwain is a Chicago-based freelance writer who has contributed health-related articles to several national magazines.