Getting C. Diff Under Control

Excerpt from RN Web
By TERRI METULES, RN, BSN, clinical editor

Clostridium difficile, the most common cause of antibiotic-associated diarrhea, poses a huge threat to hospitalized patients. But do you know all you should about the new therapies that are in the pipeline, and what you can do to protect your patient - now?

Surfing the Web, I stumbled upon a professional chat room in which a nurse had asked for information about Clostridium difficile, the spore-forming, anaerobic bacillus that causes most cases of antibiotic-associated diarrhea. The response she received from a colleague was that "C diff," as it's nicknamed, is the "in" bacteria and companies are making a lot of money selling drugs to treat it.

A physician in the same chat room disagreed with a nurse's decision to place a patient diagnosed with C. difficile-associated disease (CDAD) in isolation. He told the nurse that "C. difficile isn't infectious." The nurse asked if anyone "knew for sure" if CDAD is no longer considered contagious, and wondered if there was research to back it up.

As I read on, it became clear to me that there was more confusion than clarity surrounding C. difficile. The organism is indeed infectious; it can easily be spread from patient to patient, and is now on the growing list of antibiotic-resistant organisms.

C. difficile's toxins damage the gut wall, causing problems ranging from mild diarrhea to severe pseudomembranous colitis, toxic megacolon, and bowel perforation. Immunocompromised patients are among those at highest risk for severe infection.

The good news is that there are several developments underway—a new drug, a vaccine, and a rapid test for detecting the bacteria—that could bring an end to C. difficile's scourge. But until these developments (summarized in "New weapons are poised to combat CDAD") make their way to the bedside, nurses need to know how to stem the spread of this infection and help patients who have the disease heal.

C. difficile is destructive when given the chance:

The organism known as C. difficile inhabits the gut of up to 70% of healthy newborns and 3% of healthy adults, so it hasn't always been considered a pathogen. (This may be why some practitioners don't consider it infectious.) The microbe's destructive nature emerged only after the use of broad-spectrum antibiotics came into vogue.

During normal human growth and development, bacterial competitors crowd this slow-growing anaerobe out of the gut of the majority of people. Whatever C. difficile remains is held in check by the gut's normal flora. However, if the bacterial competition is killed off—which is what happens when patients are given broad-spectrum antibiotics—C. difficile can grow out of control and CDAD develops.

Symptoms include loose, watery, and foul-smelling stools that smell like horse manure; crampy abdominal pain; and in most cases, fever. Severe diarrhea is confirmed when there is more than 10 stools a day. Patients can develop signs and symptoms within the first week of antibiotic therapy and up to 10 weeks after its discontinuation.

For antibiotics to "cause" CDAD, a person must be exposed to the C. difficile organism or already have the bacteria in his colon. Most people who come into contact with C. difficile do so during a hospital stay. Studies show that more than 30% of all hospitalized patients in the United States become infected with C. difficile. Of those infected, 60% are diagnosed after admission. Also noteworthy: A full 97% of the cases of diarrhea acquired in ICUs are caused by C. difficile.

Hospitals have become the major source of C. difficile infection because infected patients shed thousands of these organisms in each stool. The expelled organisms rapidly develop a protective coat and live for months as spores, cocooned from conditions that would normally kill them. Animal studies show that it takes only two C. difficile bacteria to trigger infection. If that's also the case in humans, almost all hospitalized patients may be at risk.

C. difficile spores have been cultured from specimens taken from bed rails, blood pressure cuffs, thermometers, telephones, tabletops, and other surfaces in the rooms of infected patients. Healthcare workers caring for an infected patient, pick up the spores on their hands, and inadvertently spread them to other patients. Nosocomial outbreaks of C. difficile are common and are directly related to poor handwashing by caregivers.

Taking a look at who's at risk:

Not all patients exposed to C. difficile will become ill. Infants generally don't because the cells of a newborn's colon are too immature to bind the toxins produced by the bacteria. As the "Bacterial invasion of the gut wall is progressive" box explains, these toxins cause the damage seen in CDAD.

Normal gut flora and a healthy immune system usually prevents exposed adults from acquiring the microbe. However, some adults become colonized, meaning that C. difficile is present in their colon, but is either not causing damage or the damage is too insignificant to cause symptoms. These adults are referred to as asymptomatic carriers.

Because antibiotics destroy the normal gut flora that keeps C. difficile in check, or out of the gut in the first place, any adult patient taking antibiotics is at risk for developing CDAD. Any antibiotic can cause it, including those that might be used to treat it. The most potent offenders are amoxicillin (Amoxil, Trimox, others), clindamycin (Cleocin), and all generations of the cephalosporins, such as cefazolin sodium (Ancef, Kefzol, others), cefuroxime sodium (Zinacef, Kefurox), and ceftriaxone sodium (Rocephin).

While antibiotic therapy is the major cause of CDAD, any breach in the gut's mucosal layer can lead to it. CDAD has developed after nasogastric tube insertion, or during enteral feedings from the tip of the tube hitting the gut wall, enema administration, and gastric surgery. It can also develop in patients receiving chemotherapy, because of the antibiotic-like action of some antineoplastic agents.

Why some exposed adults remain asymptomatic carriers while others develop severe disease is directly related to the strength of a person's immune response to the C. difficile toxins. Patients who produce high levels of antibodies against the toxins fare better than those who don't. A poor antibody response to the toxins is associated with severe, prolonged, and recurrent CDAD. Groups at highest risk for severe CDAD include the elderly, the immunocompromised, and the critically ill.

Confirming a diagnosis can take a bit of time:

Endoscopy is the best way to confirm a fulminant case of CDAD when a rapid diagnosis is needed. For example, pseudomembranous plaques found during endoscopy can confirm CDAD in patients with suspected antibiotic-associated diarrhea. Endoscopy is less useful in mild to moderate diarrhea; results may be normal in mild cases and may show nonspecific colitis in moderate cases.

The gold standard for diagnosing CDAD is the tissue culture cytotoxicity assay. For this test, a stool sample is obtained and tested for toxins. The test takes 48 hours to complete.

While it's the most accurate test for "ruling in" CDAD, a negative cytotoxicity test does not completely rule out the disease. If the stool sample isn't fresh or placed on ice immediately, the toxins will be destroyed and the accuracy of the results affected.

Therefore, the lab test most widely used to detect C. difficile toxins is the enzyme-linked immunoassay (EIA). It's less expensive, needs no special equipment for testing, and provides results in two to six hours. While the EIA is highly specific, it's not as sensitive and, therefore, not as accurate as the cytotoxicity assay. In addition, the most frequently used EIA detects only one of the two toxins produced by C. difficile: toxin A. The EIA of choice should have the capacity to detect both toxin A and its counterpart—toxin B.

Treatment depends on the severity of CDAD:

Early identification and treatment of CDAD can often keep diarrhea from becoming severe. For a patient with only mild diarrhea, discontinuation of the offending antibiotic may be all that's needed.1,5,7 For patients who have or are at high risk for severe disease, or who must remain on antibiotics for another condition, the current treatment of choice is an antibiotic.

We don't fully understand why some antibiotics are more strongly associated with the development of CDAD than others. However, we do know that narrow-spectrum antibiotics, such as metronidazole (Flagyl) and vancomycin HCl (Vancocin, Vancoled), rarely cause diarrhea; therefore, these two antibiotics are the drugs of choice for treating CDAD. When either metronidazole or vancomycin is used to treat antibiotic-associated diarrhea, the diarrhea resolves within 10 days of initiating therapy in 96% of the cases. However, 25% of patients relapse when the antibiotic is stopped.

Metronidazole is preferred over vancomycin because it can be given orally or parenterally, is less expensive, and, unlike vancomycin, isn't associated with the development of resistant strains of enteric bacteria. When used to treat CDAD, the usual dose of metronidazole is 250 – 500 mg three or four times a day for 10 – 14 days. Adverse effects such as nausea, vomiting, and a metallic taste make oral metronidazole less appealing to patients than vancomycin.

Vancomycin is given orally to treat CDAD. When given IV, the drug won't reach concentrations high enough to eradicate C. difficile from the gut. Because vancomycin is poorly absorbed in the gut, it has few side effects and is, therefore, the drug of choice for treating CDAD in pregnant women and children under 10.

When used for mild to moderate diarrhea, the recommended oral adult dose of vancomycin is 125 mg four times a day for 10 days. Vancomycin is also the drug of choice for treating CDAD in critically ill patients and in patients who have pseudomembranous colitis, ileus, or colonic dilation. The recommended dose in these cases is 500 mg four times a day for 10 days.

Other strategies and treatment options:

In addition to giving vancomycin or metronidazole, there are other things you can do to stop or slow down the progression of CDAD. If a patient must remain on antibiotics for another condition, that antibiotic may need to be changed to one that's less likely to cause diarrhea. Examples include IV aminoglycosides, macrolides, or rifampin (Rifadin, Rimactane).

Make sure a patient with CDAD doesn't receive medications like loperamide HCl (Imodium) or diphenoxylate HCl plus atropine sulfate (Lomotil). By slowing down gastric motility, these drugs can impede toxin removal from the gut, triggering toxic megacolon.

Cholestyramine resin (Questran) has been used as an adjunct to treatment because it binds toxins A and B, similar to the way it binds cholesterol. It's been used with moderate success—but only in chronic cases. Because cholestyramine also binds with vancomycin, the two drugs should be given at least an hour apart.

Intravenous human immunoglobulin (IVIG) has also been studied as a treatment for CDAD. One study showed that it boosted the anti-toxin antibody production in patients with severe colitis who didn't respond to metronidazole or vancomycin. IVIG is now considered an alternative treatment for severe cases.

Probiotics, which are live microorganisms, are often given to bolster the gut's normal flora. They've been used with some success to manage recurrent infection. The probiotics most frequently used to treat CDAD include Lactobacillus GG, which is a concentrate that can be added to skim milk; Lactobacillus acidophilus, found in yogurt; Saccharomyces cerevisia, which is found in brewer's or baker's yeast; and Saccharomyces boulardii, a nonpathogenic yeast that's given in capsule form.

Emergency surgery is the last-ditch effort in life-threatening cases of CDAD. It may be necessary, for example, for patients with severe colitis that doesn't respond to medical therapy or for patients with impending bowel perforation. The operation of choice is subtotal colectomy and ileostomy.

Supporting the patient with CDAD:

The nurse's role in caring for patients with CDAD includes supporting the patient while he fights the infection, monitoring for complications of the disease, and preventing a nosocomial outbreak of C. difficile.

A patient with moderate to severe diarrhea is at high risk for dehydration and electrolyte imbalance because inflamed areas of the bowel can no longer absorb fluid and electrolytes. In addition, cramping abdominal pain may make the patient reluctant to eat or drink.

Monitor your patient for signs of dehydration, such as sunken eyes, dry mucous membranes, elevated urine specific gravity, and a drop in blood pressure greater than 10 mm Hg when taken immediately after the patient has risen from a lying to a sitting or standing position. Late signs of dehydration include tachycardia and sustained hypotension.

Because lethal dysrhythmias can arise from an electrolyte imbalance, assess the patient's heart rate for irregularities. Also monitor intake and output and serum sodium, potassium, calcium, magnesium, and phosphorus levels. Be prepared to administer oral or IV fluids and electrolytes. In addition, watch for signs of systemic infection, including a rise or drop in body temperature.

Prevent the spread of C. difficile:

Use contact isolation precautions when caring for patients known to have CDAD, as well as those suspected, or colonized with C. difficile. That means wearing gloves whenever you enter the patient's room and when touching the patient, anything he touches, or any surface or piece of equipment in his room.

Strict handwashing is imperative, and one way to prevent the spread of this infection. Wash your hands before and after all patient contacts, and between procedures on the same patient. Wash thoroughly after removing gloves in contact with any body fluids, non-intact skin, or potentially contaminated equipment and surfaces.

Wear gowns and masks when changing grossly contaminated linens. Place all soiled linen in leak-proof bags marked biohazard or marked in a way that indicates the bags contain potentially infectious material.

If possible, use disposable equipment, such as thermometers or blood pressure cuffs when caring for infected patients. Clean all surfaces in the infected patient's room with a hypochlorite-based disinfectant.

Finally, educate all staff about CDAD, how it develops, how it's treated, and how to prevent the spread of infection. Misconceptions about C. difficile clearly abound, as I found during my visit to a professional chat room. But armed with this article, you can clear up confusion wherever you find it.