Clostridium difficile–Associated Disease: Diagnosis, Prevention, Treatment, and Nursing Care

The authors provides an overview of Clostridium difficile—associated disease, its mode of transmission, diagnosis, prevention, and current methods of treatment.I magine that your beloved grandmother has been hospitalized with a stroke. You are devastated as you imagine the lifestyle changes that will shortly ensue. You contemplate rehabilitation, physical therapy, and extended care possibilities. Her progress is good, except for a small bout of pneumonia that is successfully treated with a course of oral antibiotics. Therapy resumes, as do discussions about moving forward. Then she begins to complain of abdominal pain, has a mild fever, and experiences multiple liquid, foul-smelling stools. She has been placed in isolation, and you don gloves and gown and lean over to listen as she whispers “I have something called C-diff.”Clostridium difficile–associated disease (CDAD) is a confounding complication. Experienced by patients in extended care facilities, acute care areas, and intensive care units, it has become increasingly prevalent in the United States since 2003, when 178000 cases were diagnosed.1 The rate of CDAD is 7 times higher in persons more than 65 years old than in persons from 45 to 64 years old.1 Possible explanations for these different rates include greater exposure to hospitals and extended care facilities, greater use of antimicrobial drugs, and decreased host defenses among older persons.2 CDAD has become so rampant that reporting infection with C difficile has become mandatory in Ohio.3 Conservative estimates suggest that patients with CDAD incur at least $3669 extra in hospital costs and spend at least 3.6 additional days in the hospital.4 Costs may exceed $600 million per year in short-term care facilities alone.1Nurses must care for patients with CDAD and are therefore in position to prevent its spread. In this article, I provide an overview of this disease, its mode of transmission, diagnosis, prevention, and current methods of treatment. I also discuss the nursing care of patients who have CDAD.CDAD is used to describe a constellation of illnesses caused by the toxins, A and B, produced by the C difficile bacillus. The illnesses include diarrhea, pseudomembranous colitis, toxic megacolon, perforation of the colon, and, in some instances, sepsis.5The emergence of a new, more virulent strain of C difficile partly explains the recent increase in CDAD. This new strain, the North American pulsed-field gel electrophoresis type I (NAP I) is more virulent and can produce greater quantities of toxin A (16 times more) and toxin B (23 times more) than other strains.2,5 Binary toxin, a third toxin, is also produced by NAP I, although its significance is unknown.5 Researchers6 in Quebec identified use of fluoroquinolones as the most important risk factor in the development of this new strain of C difficile. Other factors associated with diarrhea, such as predominant use of high-risk antibiotics, reduction in housekeeping staff, increased nursing workloads, antiquated facilities, and general changes in hospital populations (ie, increased number of immunocompromised, debilitated, and elderly patients) may also be contributing factors.7Clostridium difficile is an anaerobic, spore-forming, gram-positive bacillus.8 The spores are resistant to many types of disinfectants, heat, and dryness and may persist for months on surfaces such as bed rails, commodes, electronic thermometers, stethoscopes, skin folds, and the hands of caregivers.2 The spores can cause disease in persons at high risk for CDAD.Transmission of C difficile is via the fecal-oral route (see FigureF1). In healthy persons, growth of C difficile is kept in check by normal flora in the gut. Possibly, use of antibiotics and medications that decrease stomach acidity, such as proton pump inhibitors, cause C difficile bacteria to proliferate.9Once in the colon, C difficile, its growth unchecked by normal flora or stomach acid, produces 2 toxins: an enterotoxin (toxin A) and a more potent cytotoxin (toxin B).10,11 Toxin A activates macrophages and mast cells,11 which release inflammatory mediators. The mediators cause disruption of the cell wall junction, resulting in increased permeability of the intestinal wall and subsequent diarrhea.5,11 Meanwhile, toxin B causes degradation of epithelial cells in the colon.5 As the colitis worsens, purulent and necrotic debris accumulates and forms characteristic ulcers, the pseudomembranes11 (see FigureF1).A number of risk factors for CDAD, including the use of antimicrobials, particularly fluoroquinolones, have been identified6 (Table 1). Patients who are elderly, have severe underlying disease, have nasogastric tubes in place, have long hospital stays, or are taking proton pump inhibitors and histamine receptor antagonists are at particular risk.9CDAD can be mild, severe, or systemic (Table 2). Mild disease is characterized by nonbloody diarrhea, occasionally accompanied by cramping in the lower part of the abdomen without systemic signs and symptoms.5 The diarrhea is often mucoid and foul smelling. Some have described it as having a characteristic “barnyard” odor.13 Associated signs and symptoms include nausea, dehydration, and low-grade fever. Leukocytosis may occur.5,10Colitis occurs with severe forms of the disease and causes profuse diarrhea and abdominal pain, often with fever, nausea, abdominal distension, and dehydration. Characteristic raised white and yellow plaques may be visualized during sigmoidoscopy.5,10 Composed of neutrophils, fibrin, mucin, and cellular debris, these pseudomembranes appear on inflamed colonic mucosa as raised nodules, usually 2 to 10 mm in diameter.22Complications such as sepsis, volume depletion, electrolyte imbalance, hypotension, peritonitis, paralytic ileus, and toxic megacolon may be present in systemic CDAD.5 Hypoalbuminemia and ascites may also be evident.23 A decrease in diarrhea may occur in systemic disease as a result of toxic megacolon or paralytic ileus.5,10 Computed tomography scans may show thickening of the colon wall or obliteration of the lumen.23 Patients with systemic disease associated with megacolon may require surgery.5,10Diagnosis of CDAD is based on signs and symptoms, verification of the presence of toxins A and B in stool cultures, and, in many instances, detection of pseudomembranous colitis. Pseudomembranous colitis is verified via colonoscopy. Because of the risk of perforation and the cost of this test (mean, $1656 per test),24 experts suggest that colonoscopy be used with caution, and only for patients with severe colitis of unclear origin.10,23Stool cultures are highly specific and sensitive for detection of toxin B; however, they are time intensive and are not often used.22,23 The enzyme-linked immunosorbent assay test for toxin A or toxins A and B has excellent specificity, and results are usually available in about 2 hours.22,23 The sensitivity, however, is only 75% to 85%. Therefore, cultures of serial stool samples collected on different days are suggested, especially in suspicious cases in which the initial samples are negative for C difficile.23The large quantity of stool produced in CDAD allows ample opportunity for specimen collection. Of note, the toxins themselves are unstable at room temperature; therefore, false-negative results may occur in samples that are not tested within 2 hours of collection.25 For that reason, ensuring that stool samples are quickly sent for testing once obtained is prudent. Because the stools themselves harbor C difficile spores, great care must be taken to avoid contaminating surfaces with the specimens. Pimetel23 suggests that specimens be sent and tested before antibiotic therapy is started and that contact isolation be initiated on the basis of signs and symptoms, rather than waiting for culture results. Sunenshine and McDonald5 suggest that only watery or liquid stools be tested. A false-positive result could indicate that C difficile colonization is present. Infection is not likely in persons who do not have diarrhea.5Patients treated with antibiotics must be closely monitored for possible infection with C difficile. Patients who are elderly, have severe underlying illness, are immunocompromised, or have undergone surgery of the gastrointestinal tract also require heightened vigilance.Prevention of CDAD, however, entails multidisciplinary efforts to stem the disease for all patients. Three elements are required for prevention of CDAD: proper hand washing, contact isolation, and environmental measures.Hands must be washed with an antimicrobial soap for at least 15 seconds. Although generally beneficial, alcohol-based hand rubs may not be effective against C difficile spores.2 A paper towel should be used to turn off the faucet. Hands should be washed before and after contact with a patient and after glove removal. This technique must be taught to all of the patient’s family members as well as the patient. Reminders to healthcare workers are also important. In one study,26 effective staff education programs resulted in a significant reduction in infection rates. Recommendations include clustering of nursing care, hand hygiene education, and ongoing audit and surveillance programs.26Guidelines of the Centers for Disease Control and Prevention mandate contact isolation for all patients with CDAD. Private rooms are recommended if available; however, if necessary, 2 patients with CDAD can be placed together. All persons entering the patient’s room, including the patient’s family members, must use protective gowns and gloves. Use of dedicated equipment such as thermometers and stethoscopes is also recommended.2Such imposed isolation requires compassionate yet firm teaching and support for patients and their family members. All hospital employees, including physicians, therapists, clergy, and technicians, must abide by isolation guidelines, no matter how brief their visit.Spores of C difficile tend to thrive on hospital surfaces. For that reason, stringent daily cleaning of all hospital surfaces likely to be contaminated with feces is essential. A hypochlorite-based disinfectant that has been registered with the Environmental Protection Agency or a 1:10 bleach solution is recommended.2 Frequently touched surfaces such as doorknobs, light switches, call lights, television remote control devices, soap dispensers, faucets, bed rails, and telephones also require thorough daily cleaning. Hospital policies regarding dedicated equipment, dishes, linens, waste, and patient transport should be in place and enforced. Nondisposable equipment such as glucose meters, cardiac monitors and electrocardiography and x-ray machines should be disinfected according to manufacturers’ guidelines.Nurse managers at a hospital in England attribute a significant decrease in C difficile infection to changes in environmental policies and replacement of outdated commodes and mattresses. A decrease in length of stay and cost savings were also realized as a result of these changes.27The various treatments suggested for CDAD and their efficacy are matters of much debate. A review of basic and more recent innovative treatments follows (Table 3). As Bartlett14(p429) notes “It can be safely concluded that all of these treatments work some of the time, none work all of the time.” This comment reflects the confounding nature of CDAD and the necessity of impeccable nursing practices.The first treatment for CDAD is cessation of the suspected causative antibiotic.23 Although stopping the antibiotic may be effective, the reason the antibiotic was prescribed in the first place should be considered, and monitoring for recurrence or worsening of the underlying infection is essential.Oral metronidazole, 250 to 500 mg 4 times a day for 7 to 14 days, is generally recommended as an initial treatment.29 Metronidazole can also be given intravenously.30 Administered by either route, the same dosage provides bactericidal levels of the drug in the bowel lumen.Although equally effective as metronidazole when given orally,30 vancomycin, standard dosage 1 g/d for 10 days, is more expensive, and is therefore reserved for patients who can not tolerate metronidazole, are pregnant or breastfeeding, or have severe cases of CDAD.23,29,30 Alternative vancomycin dosing strategies may be effective for treatment of recurrent CDAD.31 A pulsed dosing regimen, intermittent delivery of between 125 and 500 mg every 3 days, and tapered dosing, administering the antibiotic over long periods at decreasing doses, may in some instances effectively eradicate vegetative C difficile cells.31In addition to its greater cost, a disadvantage of vancomycin is the occurrence of vancomycin-resistant strains.23 Intraluminal concentrations of vancomycin cannot be achieved by intravenous infusion as they can with metronidazole.30 However, vancomycin can be given via a nasogastric tube or as an enema.30 Instilling vancomycin as an enema can be challenging, particularly when a patient is experiencing diarrhea. This route is suggested as an adjunct for patients with persistent or severe CDAD, severe ileus, or fulminant colitis.15 The medication can be given at dosing intervals of 4 to 12 hours, with doses of 2 to 3 g/d, by using an 18F Foley catheter or a soft 6F pigtail catheter. The risk of bowel perforation, inherent any time an enema is given, mandates particular vigilance for these patients. Ideally, the enema should be retained for 60 minutes. Vancomycin can also be given via colostomy, ileostomy, or during colonoscopy.15Oral rifampin has been given with metronidazole as an adjunct therapy. A prospective, randomized, single-blind study16 of 39 patients was conducted to compare the efficacy of metronidazole therapy alone with that of metronidazole plus rifampin. The researchers could not demonstrate a therapeutic benefit of this drug combination and halted their study early, citing study futility and urging better treatment protocols.16More promising results are suggested by a study17 in which oral metronidazole was compared with nitazoxanide. A nitrothiazolide, nitazoxanide works by blocking anaerobic metabolism and is used to treat intestinal infections caused by the protozoa Cryptosporidium and Giardia. Patients receiving nitazoxanide were given 500 mg every 12 hours for 7 or 10 days. Those receiving metronidazole received 250 mg every 6 hours for 10 days. For both groups, the time of resolution of their signs and symptoms, clinical response after 7 days of treatment, and sustained response after 31 days were determined. Initial data suggest similar effectiveness for metronidazole and nitazoxanide. Further studies are being designed to compare this new medication with vancomycin.17Not yet available commercially, tolevamer can also be considered for treating CDAD. A soluble, high-molecular-weight, anionic polymer, tolevamer works by binding C difficile toxins A and B.18 Suggested for use with mild to moderately severe CDAD, tolevamer is given orally 3 times daily for a total of 3 to 6 g per day. Initial trial results indicted that the polymer was fairly well tolerated, provided resolution of signs and symptoms in 67% of patients, and was associated with a lower incidence of recurrence than was vancomycin.18 Resolution of diarrhea was comparable to that achieved with vancomycin; however, tolevamer is also associated with an increased risk of hypokalemia.18Immunoglobulin has been proposed as a treatment for intractable and severe cases of CDAD. In one study,19 patients were given 1 to 6 doses, ranging between 300 and 500 mg/kg. Of 5 patients with refractory disease, 3 had resolution of signs and symptoms within 11 days. Although this treatment looks promising, immunoglobulin is expensive and in short supply.19Probiotics are live organisms meant to treat particular diseases, including Helicobacter pylori infections, acute gastroenteritis, and antibiotic-associated diarrhea, including CDAD. The most commonly used probiotic agents produce lactic acid and are present in normal microflora. Examples include Saccharomyces boulardii, Lactobacillus acidophilus, and Lactobacillus plantarum.32 Many studies of probiotics have been done. Sullivan and Nord32 suggest that although S boulardii was somewhat effective, particularly in preventing recurrent CDAD, further studies are needed. Dendukuri et al20 similarly determined that evidence was insufficient to recommend the routine clinical use of probiotics to treat CDAD in adults.Use of corticosteroids in a child with refractory CDAD has been described.33 Typically used for acute flare-ups of inflammatory bowel disease, corticosteroids may also be beneficial in CDAD. Further studies are needed.A potential means of replacing normal bowel flora is transplanted stool. In one study,28 18 patients were given of stool via a nasogastric were persons who had not received antimicrobial therapy for 6 had contact with the patient (ie, or significant family or were healthy patients in the study of however, the patients a that of normal bowel Further studies are suggested before stool are used Although and may to be considered, et that the patients in the study were to the of stool that to paralytic ileus, toxic megacolon, or treatment may require pseudomembranous colitis is associated with high to hypotension, acute and in concluded that total abdominal within hours of of fulminant pseudomembranous colitis rates. therefore support is a by patients hospitalized for other therefore, must be monitored and treated for their underlying In they must be closely monitored for white cell fever, abdominal pain, and, most diarrhea. The of care include prevention of CDAD, and treatment of the disease, of and prevention of skin patients with CDAD require monitoring of signs and In addition to gastrointestinal monitoring of and is in to and treat systemic to treat and by is essential. Patients with liquid stools have with to skin and of is for patients with CDAD. and and levels of and must be monitored and as needed. of and C should be as Patients should be monitored for clinical of dehydration, including decreased increased rate and of decreased of and decreased with increased specific Patients should also be for the presence of skin with and should be intravenous therapy based on of and oral should be care should be provided and patients should be to avoid the use of and nausea, and to fulminant disease could result in hypotension, and Because agents such as and may patients with CDAD to toxic megacolon, these are not Use of should also be liquid bowel associated with abdominal pain, or cramping are cause for isolation may to can these Therefore, it is to for pain, as provide skin and care, and for or during isolation can be by that include ongoing of isolation, to and and the patient’s of of skin is of the and of stools in patients with CDAD. colonization with and to skin of skin care include skin exposure to and a that and are the normal skin of and provide should be The should be daily and with bowel or that as should be after A possible of is A recent the for staff and in the use of and in the prevention of this of and may also be such as the a catheter with a and a The catheter is the and when used can and liquid or stool from the should be especially with to the length of time this treatment may be recommended and before that CDAD may in patients care to provide and thorough of most at nursing care must be provided to with CDAD (Table In the “It may a to as the first in a hospital that it should do the no Prevention is the most important treatment.

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