Clostridium difficile Infection in Solid Organ Transplant Patients

Authors: Sarah E. Ward, MS and Erik R. Dubberke, MD, MSPH

Clostridium difficile is an anaerobic, Gram-positive, spore-forming bacillus. It is a human pathogen that causes infectious diarrhea and antibiotic-associated colitis. C difficile causes 10% to 25% of antibiotic-associated diarrhea cases in hospitalized patients and more than 90% of cases of antibiotic-associated pseudomembranous colitis (5). It is among the most common healthcare-associated pathogens (18) and is recognized as the most common cause of nosocomial infectious diarrhea (27). C. difficile injures colonic mucosa and causes inflammatory diarrhea via its two exotoxins, toxin A and toxin B, which trigger a cytotoxic response, neutrophilic infiltrate, and cytokine release (5). The terms C. difficile-associated disease (CDAD) and C. difficile infection (CDI) are interchangeable and refer to patients with symptoms of infection due to C. difficile.

Diarrhea is a common problem in solid organ transplant recipients, with incidence rates of 10% to 20% (3). Solid organ transplant recipients who develop diarrhea are at risk for dehydration, malnutrition, skin breakdown, and changes in immunosuppression levels (29).

The incidence of CDI in solid organ transplant recipients is generally comparable to other post-operative patients, but varies according to the organ that is transplanted (52). Solid organ transplant recipients have unique risk factors that might contribute to more severe CDI. Fulminant colitis develops in up to 13% of solid organ transplant recipients with CDI (13). The incidence of CDI in solid organ transplant recipients is highest in the three months following the transplant procedure. This is likely a consequence of the recipient’s frequent exposures to antimicrobials, healthcare settings, and immunosuppressants. Late-onset CDI occurs months to years after the transplant and is associated with antimicrobial exposure, intensified immunosuppression to treat graft rejection, and repeat healthcare exposure.

Health care exposure is important because C. difficile is primarily a healthcare-acquired pathogen. Approximately 3% of patients without recent healthcare exposures are colonized with C. difficile and the risk of acquiring C. difficile after admission to an acute care facility is 8% per week. Overall, approximately 20% of hospitalized patients are colonized. In non-transplant patient populations, 30% of patients who acquire C. difficile progress to CDI and 70% remain asymptomatic (31). The incidence of CDI in all hospitalized patients is 1–2% and rising (38).

The incidence in solid organ and hemapoietic stem cell transplant recipients ranged from 1% to 31% (15, 26, 54). Notably, infection severity in all patient groups is rising. The increases in CDI incidence and severity are associated with the emergence in 2000 of a previously uncommon, hyper-virulent strain of C. difficile (59). This strain is known as North American pulsed field gel electrophoresis type 1 (NAP1), restriction enzyme analysis (REA) BI strain, and PCR-ribotype 027 strain (40).

The NAP1 strain possesses several important virulence factors. It is a toxinotype III strain of C. difficile. Toxinotype III strains of C. difficile have a non-functional tcdC gene. This gene is believed to be involved in down regulation of toxin production (59). In vitro, the NAP1 strain produces 16 times more of toxin A and 23 times more toxin B than the C. difficile toxinotype that has historically caused disease in humans. The NAP1 strain also produces a third toxin called binary toxin but the mechanism of this toxin and its role in CDI has not yet been elucidated. NAP1 also displays high level resistance to flouroquinolone (40). It is not yet known how the NAP1 strain affects CDI incidence and severity in solid organ transplant recipients relative to the general hospital population.

Exposure to antimicrobials is the most significant risk factor for development of CDI in the healthcare setting (8). CDI has been associated with most antimicrobial classes, but clindamycin, third-generation cephalosporins, and aminopenicillins are associated with high risk of developing CDI. In addition, fluoroquinolones have recently been identified as high-risk agents (48). Exposure to multiple antimicrobials and/or extended courses of antimicrobials increases risk. Despite this, only 80% of solid organ transplant recipients who develop CDI have recent history of microbial exposure (8) compared to ≥90% for other hospitalized patients. This might be explained by the many other risk factors for CDI that solid organ transplant recipients have such as high severity of underlying illness and immune suppression.

Proton-pump inhibitors (PPIs) might also contribute risk for developing CDI (12, 16, 17). Hospitalized patients who use proton-pump inhibitors (PPIs) are twice as likely to develop CDI (18). Many solid organ transplant recipients receive medications that suppress gastric acid. The stomach’s acidic environment is fatal to vegetative C. difficile and might prevent the organism’s spores from germinating (63). It is plausible that proton-pump inihibitors might disturb protective indigenous gastrointestinal flora because proton-pump inihibitors do have antimicrobial activity (56).

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Clinical manifestations of C. difficile colonization range from asymptomatic colonization, non-specific watery diarrhea, pseudomembranous colitis, to toxic megacolon (24). The most common clinical presentation of CDI (i.e. symptomatic infection) is diarrhea during or soon after antimicrobial therapy given for other indications. The clinical standard for suspecting CDI is clinically significant diarrhea, usually defined as 3 or more loose stools per day for 1 to 2 days (50). Diarrhea is usually watery although mucoid or soft stools also occur. Stools might have a characteristic foul (“barnyard”) odor. Grossly blood stool is uncommon. Onset might be days after antibiotic therapy is initiated or as long as eight weeks after therapy ends (31). For mild to moderate disease, diarrhea is usually the only symptom, but patients might have low grade fever and mild abdominal pain and/or cramping. Patients with severe disease can have more than 10 bowel movements per day (6).

Systemic symptoms are usually absent in mild disease but are common in moderate or severe disease (55). Patients with manifestations of severe disease can have fever, moderate to severe abdominal pain and/or cramping, abdominal distention, peritoneal signs, and systemic toxicity. A white blood cell count >15,000 cells/mm3 and acute renal failure are other signs of severe CDI. Paradoxically, some patients with severe or complicated CDI do not have diarrhea and present with ileus. In a situation that involves ileus, abdominal imaging might be useful. Radiologic features consistent with CDI include thickened colonic wall, ascites, or marked colonic dilatation consistent with toxic megacolon. Endoscopic visualization of pseudomembranes is generally considered diagnostic of CDI, but it is present in only 50% of patients at time of endoscopy. In addition, pseudomembranes are less commonly seen in patients on immunosuppressive medications (46) and CMV colitis can sometimes cause pseudomonas as well (22).

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CDI is a clinical diagnosis with laboratory confirmation. It is important to keep this in mind when interpreting test results in patients with minimal symptoms as clinical suspicion should outweigh test results. Laboratory analysis of stool samples is the standard to confirm diagnosis of CDI in patients with a clinical syndrome compatible with CDI. Laboratory testing for C. difficile is recommended for patients who have otherwise unexplained diarrhea and recent history of antimicrobial use. A variety of pathogens cause diarrhea but C. difficile is the most common infectious cause of diarrhea in patients hospitalized for more than 72 hours (45). A variety of laboratory-based assays confirm the diagnosis of CDI and each has advantages and disadvantages (Table 1). No assay is 100% specific for C. difficile infection. In severe cases, flexible sigmoidoscopy can provide an immediate diagnosis.

Most U.S. institutions use commercially available enzyme-linked immunosorbent assays (ELISAs) to detect C. difficile toxins. Toxin ELISAs are easy to perform, relatively inexpensive, and results are typically available in two to four hours. Toxin ELISA specificity is generally greater than 90%, but a disadvantage is a decreased sensitivity (70%-80%) compared to other assays for detecting C. difficile or its toxins (7). Despite this modest sensitivity, the negative predictive value of a negative toxin ELISA is typically >95% (37). Automatic repeat testing after an initial test is not recommended because repeating a test in the absence of re-evaluating the patient to confirm a continued concern for CDI increases the likelihood of a false positive result. Diagnostic and treatment decisions should be based on continued clinical suspicion of disease rather than automatic retesting after an initial negative toxin assay (43, 50). It is important to keep in mind that some ELISAs detect only toxin A. These assays do not detect strains that produce only toxin B, strains that are capable of producing the same spectrum of disease as strains that produce toxins A and B.

The laboratory gold standard to detect C. difficile toxin is the cytotoxicity cell assay, however its use is limited because it is technically demanding, costly, and requires 24–48 h wait for results. Although the cytotoxicity cell assay is considered more sensitive than toxin ELISAs, the sensitivity of the cytotoxicity cell assay is not significantly greater (51). ELISAs for C. difficile toxins A and/or B have largely replaced the cytotoxicity cell assay, but the cytotoxicity cell assay remains the most sensitive test available to detect toxin B (57).

Polymerase chain reaction (PCR) for C. difficile is being investigated as a diagnostic strategy. Real-time PCR detects toxigenic C. difficile in stool in a few hours with higher sensitivity than toxin ELISAs and cytotoxicity cell assays (47). At present two commercially produced assays are available for use in the US and several more assays are on the way. The potential disadvantages of PCR are that it is expensive and not all labs are able to perform PCR because they do not possess the specialized and dedicated equipment.

Stool culture, when properly performed, is the most sensitive method to detect C. difficile. However, stool culture is expensive and impractical for swift diagnosis: culturing is labor and time intensive, turnaround is >48 hours, and culturing does not differentiate toxigenic and nontoxigenic strains (62). Because culture does not differentiate between toxin and non-toxin producing strains, it is also necessary to test C. difficile isolates for toxin production.

Another available assay type detects C. difficile glutamate dehydrogenase (GDH). The assay is inexpensive, rapid, and easy to perform. The disadvantage of this assay is that it has poor specificity (~50%) because it does not differentiate between toxin producing and non-toxin producing strains of C. difficile. In addition, other bacteria can also produce glutamate dehydrogenase and the assay might detect those organisms. Therefore glutamate dehydrogenase assays should not be used alone to diagnose CDI. Because of concerns of low sensitivity of toxin ELISAs and the high cost and turn-around time for cytotoxicity assays and stool culture, some investigators have evaluated the use of glutamate dehydrogenase assays as an initial screening test (57). In this two step process, stool is initially screened with the glutamate dehydrogenase assay. If the result is negative, no further testing is performed. A positive result, however, is followed by testing with the cytotoxicity cell assay or stool culture. This approach decreases costs compared to using only the cytotoxicity cell assay or stool culture, but there are concerns the glutamate dehydrogenase might not be sufficiently sensitive to utilize as a screening test (20).

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The most important risk factor for CDI in hospitalized patients is disruption of colonic flora. Colonic flora protects against both colonization with C. difficile as well as development of CDI if colonization occurs. The mechanism behind the colonic flora protective effect is unclear but might be related to competition for nutrients and/or bile acid metabolism (53). Colonic flora is most commonly disrupted by antimicrobials, but agents that alter gut motility, chemotherapy, and surgery can also alter colonic flora. The risk associated with any particular antimicrobial is based on the ability of the antimicrobial to alter the colonic flora, the frequency of antimicrobial use, and C. difficile resistance to the antimicrobial (if C. difficile exposure occurs while patient is still receiving the antimicrobial).

As C. difficile colonizes and replicates, it releases exotoxins into the colonic lumen. Pathogenic strains of C. difficile produce two large, single-unit exotoxins: Toxin A, an enterotoxin, induces fluid secretion into the intestinal lumen and causes mucosal damage and inflammation in vivo; and Toxin B, a potent cytotoxin, causes mucosal damage and is a potent inducer of neutrophilic inflammation. The homologous toxins have similar modes of intracellular operation, but different cell receptor specificity. The toxins bind to colonic cell membrane receptors and are endocytosed. Interaction between the toxins and surface receptors in the colonic mucosa result in actin filament degradation which induces cytoskeletal disruption and cell death. This leads to necrosis and subsequent cellular debris that sloughs into the colonic lumen. Contact with the submucosa induces localized edema and neutrophil activation. This process leads to pseudomembrane formation, characterized by a protein-rich exudate that consists of neutrophils, monocytes, and cellular debris. In addition, both toxins and other surface proteins further induce an inflammatory response by triggering cytokine release from monocytes and dendritic cells.

A host's immune response to C. difficile and its toxins appears to play an important role in determining disease expression. The risk of symptomatic disease is higher in newly exposed and infected patients, possibly because people who are already colonized have pre-existing immunity to C. difficile toxins. After infection, the patient’s immune response to toxins appears to play a role in determining whether or not a person becomes asymptomatically colonized or whether disease develops. High titers of serum or intestinal antibodies against toxin A are associated with asymptomatic carriage of toxigenic C. difficile with shorter and less severe episodes of C. difficile diarrhea (35, 36).

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Oral vancomycin is the only FDA-approved treatment of C. difficile, but metronidazole has considerable historical use. CDI severity can generally be divided into three categories for treatment considerations: mild or moderate, severe, and severe disease with complications (Table 2) (11). Mild-to-moderate CDI can be loosely defined as diarrhea and abdominal cramping that is not accompanied by systemic symptoms. Indictors of severe disease include profuse diarrhea, abdominal pain, leukocytosis, and fever or other systemic symptoms. Severe disease with complications includes life-threatening conditions such as paralytic ileus, toxic megacolon, and multiorgan failure.

Discontinue the precipitating antimicrobial whenever possible. This alone is curative in over 20% of immunocompetent patients (25). If the solid organ transplant recipient must be treated with antimicrobials, consider changing the antimicrobial coverage to a more narrow-spectrum regimen or using antimicrobials that are less often associated with CDI. It is noteworthy that no data are available to support this recommendation. Regardless, consider a change in antimicrobial coverage if available alternatives provide acceptable treatment efficacy for the underlying infection without undue toxicity or potential drug interactions. There are no reports of CDI treatment failures due to continuation of precipitating antimicrobials, but continuation of antimicrobials is associated with an increased risk of recurrent CDI (30). In addition, provide such supportive therapy as intravenous fluids for rehydration and electrolyte replacement as necessary.

Oral metronidazole and oral vancomycin are the mainstays of treatment for CDI in both immunocompetent patients and solid organ transplant recipients. Intravenous metronidazole reaches adequate levels in the feces due to biliary excretion and exudation across inflamed colonic mucosa (9). Its use is supported by several case series, but it has not been formally studied as a treatment for CDI. Intravenous vancomycin does not reach adequate levels in the feces to treat CDI. If the immunosuppressive regimen contains tacrolimus, levels should be monitored during metronidazole treatment in order to avoid toxicity (49). Two recent studies indicate that the initial treatment choice should depend on the disease severity (39, 64). For mild-to-moderate disease, oral metronidazole is generally regarded as the drug of choice. This recommendation is based on comparable efficacy in both the general population and solid organ transplant recipients and the significantly lower acquisition costs compared to oral vancomycin. For severe CDI, oral vancomycin is becoming the preferred agent. Two randomized studies found that only 65–76% of patients with severe disease were cured with oral metronidazole, whereas cure rates improved to 85–97% with oral vancomycin (39, 64). These same two studies showed no significant difference between the two antimicrobials in the cure rate for mild-to-moderate disease. Vancomycin is typically administered at 125mg four times daily because this regimen has equal efficacy to higher doses and achieves concentrations in the stool that are hundreds of times greater than the minimum inhibitory concentration (MIC) of the organism.

In cases of severe CDI with complications, the efficacy of oral vancomycin might be limited by ileus. In these patients, higher doses of oral vancomycin may be indicated in order to increase the likelihood that adequate levels of the drug will reach the site of infection as quickly as possible. Intracolonic administration of vancomycin is also supported by case reports of patients who are unable to tolerate oral therapy. Intracolonic vancomycin use, however, might increase a patient’s risk for bloodstream infections due to colonic flora (4). When CDI is accompanied by life-threatening complications that limit oral intake or impair gut motility, intravenous metronidazole should be administered in addition to enteral vancomycin. This approach has not been well studied. Once the colitis has become this extreme, antimicrobial therapy alone might not be curative and it is important to consider surgical consultation.

Alternative Therapy

Severe CDI  

Surgical intervention has been shown to be an important component of treatment in patients with severe CDI. Up to 20% of cases of fulminant infection require surgery, but mortality remains high at 35% to 80%. Several studies show that early surgical intervention benefits patients with severe disease, bowel perforation, or multiorgan failure (14). Mortality might be reduced if surgical intervention occurs within 48 h of lack of response to medical therapy (2).

Therapeutic use of intravenous immunoglobulin (IVIG) has been attempted with variable success. IVIG contains C. difficile antitoxin antibodies; however its use is supported by only case studies and series (28). Dosages of IVIG used for fulminant CDI described in the literature range from 200 mg/kg to 500 mg/kg as a one-time dose. A retrospective analysis of 18 pair-matched patients with severe CDI did not show any benefit to combining IVIG with standard antimicrobial therapy. A limitation of this study is there was no attempt to control for the time from onset of symptoms to IVIG administration (34).

Recurrent CDI

Up to 35% of patients with CDI will have at least one recurrence (21). Treatment of the first relapse should again be based on disease severity. Comprehensive research is needed regarding the management of patients with multiple recurrences. Prolonged therapy with oral vancomycin in a tapering schedule or in pulsed doses has been successful, and is the preferred initial treatment for multiply recurrent CDI (11). Metronidazole does not achieve therapeutic concentrations in the stool in the absence of colonic inflammation and prolonged use is associated with the development of neuropathy. Therefore prolonged courses of metronidzole for treatment of recurrent CDI are discouraged.

Although there are numerous alternative and adjunctive therapies reported in the literature, supportive data are scarce (including for tapered/pulsed dose oral vancomycin). Probiotics are popular with patients and commonly used. However, no probiotic has been better than placebo when studied in a randomized fashion as adjunctive treatment for recurrent CDI. In addition, solid organ transplant recipients are at increased risk for developing infections due to the probiotic strain compared to other patient populations. Reports of successful treatment of recurrent CDI with IVIG exist. A retrospective observational study found heart transplant recipients with hypogammaglobulinemia who received IVIG seemed to be at lower risk for developing CDI (44). Bile acid binding resins have been used as well. Of note, colestipol was found to be no better than placebo for treatment of CDI and bile acid binding resins have notable drug-drug interactions (42).

Two antimicrobials available in the United States for other indications, nitazoxanide and rifaximin, have been used successfully for CDI treatment but lack United States Food and Drug Administration approval for this indication. Several studies suggest that rifaximin, which has in vitro activity against C difficile, might effectively treat recurrent disease (23, 33) but rifaximin resistance during therapy has been observed and might deter routine use.

Fecal flora restoration for treatment of CDI in immunocompetent adults (1) has been reported. Due to the lack of data regarding fecal flora restoration procedures in solid organ transplant recipients, and the potential risk of infection from infusion of fecal bacteria into the intestinal tract, it is prudent to avoid fecal flora restoration in solid organ transplant recipients outside of a study protocol.

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Patients typically show some symptomatic improvement within one to two days after initiation of appropriate antibiotic therapy for CDI. Abnormalities present when treatment is started (e.g. severity of diarrhea, fever, abdominal pain, peritoneal signs and WBC) should be monitored for improvement. Diarrhea improves in non-solid organ transplant patient populations in 3 to 6 days. Some patients might have delayed resolution of diarrhea, and this is more likely to occur with metronidazole (60). This does not represent failure; they “lag” as other parameters are improving. Persistence of diarrhea without improvement in the setting of complete resolution of other symptoms should prompt an investigation into other potential causes of diarrhea.

Patients who improve during initial metronidazole therapy, as evidenced by a decreased number of bowel movements per day and improvement in WBC count, fever, and abdominal findings, should continue to receive the metronidazole regimen on which they were started. Patients who do not demonstrate any improvement during the first 3 to 4 days of treatment, or who worsen at any point during therapy, should be switched to oral vancomycin. Consider consultation with infectious diseases, gastroenterology, and/or surgery services to evaluate possible need for alternative treatment options, an alternate route of therapy, and/or surgical intervention.

It is not recommended to repeat testing for C. difficile, especially in patients who respond to therapy. Persistence of C. difficile in stool after successful therapy is common. Persistent colonization after successful treatment is not associated with risk of recurrence and should not be used to determine the duration of therapy.

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At present, no vaccine against C. difficile is available and there is also no known effective prophylaxis against CDI. It is not recommended to treat asymptomatic C. difficile colonization. A placebo-controlled trial (32) demonstrated metronidazole was no more effective than placebo for decolonization. Although vancomycin initially decreased C. difficile colonization, it was associated with increased risk of recolonization after therapy was stopped. The only case of CDI in this study occurred in a patient who had received vancomycin. It is possible that pre-existing colonization with C. difficile protects a person against the development of CDI when s/he is hospitalized. Therefore the presence of the organism or its toxin in an asymptomatic patient would not be cause for pre-emptive therapy. Probiotics are a popular supplement, but they have not been found to consistently prevent CDI.

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C. difficile infection control involves two primary approaches: preventing transmission of the organism and its spores, and reducing the chance of developing CDI if transmission occurs. The approach to prevent transmission of C. difficile includes such traditional infection control strategies as contact precautions. Reducing the risk of developing CDI if transmission occurs involves antimicrobial stewardship.

All patients with CDI should be placed in contact precautions. Contact precautions involve donning gowns and gloves prior to entering a patient’s room. Wearing gowns and gloves is necessary even if no direct contact with a patient is anticipated. One study (41) demonstrated that C. difficile could be cultured from healthcare workers’ hands 59% of the time after workers exited the room of a patient with C. difficile. Contamination rates did not differ between the groups of workers who contacted the patient and workers who did not contact the patient. Contact precautions also includes placing the patient in isolation and using dedicated medical equipment (e.g. stethoscopes) whenever possible.

The optimal method of hand hygiene after caring for a patient with CDI is an area of controversy. Alcohol does not kill C. difficile spores. Despite this, studies have not documented an increase in CDI incidence when alcohol-based hand hygiene products are used for hand hygiene (10). Similarly, no publication has documented a reduction in CDI incidence when soap and water is used for hand hygiene after caring for a patient with CDI. These findings are likely because healthcare workers are supposed to wear gowns and gloves when entering the room of a patient with CDI, and the gloves prevent significant healthcare worker hand contamination with C. difficile spores. However, it is recommended to use soap and water for hand hygiene after caring for a patient with CDI during CDI outbreaks not controlled with other measures (18).

Another area of controversy is whether or not using a disinfectant that kills C. difficile spores is necessary. Most studies that have evaluated sporicidal disinfectants have used diluted bleach in outbreak settings in conjunction with other interventions. In this setting, it is difficult to know which intervention actually worked. Several studies in non-outbreak settings have had mixed results. One study demonstrated no decrease in the number of surfaces from which C. difficile was recovered regardless if the sporicidal or non-sporicidal (61) agent was used. At the very least, it is prudent to use diluted bleach in outbreak settings if environmental cleaning is otherwise deemed adequate.

Antimicrobial stewardship, by restricting high-risk agents or decreasing unnecessary antibiotic use, has been shown to be effective at reducing CDI incidence in both outbreak and non-outbreak settings (58). Antimicrobial stewardship has the potential to be the most effective CDI preventive measure. If there are fewer patients at risk for CDI, then fewer patients will develop CDI. If there are fewer patients who develop CDI, then there will be fewer patients who contribute to the spread of C. difficile (58). However, antimicrobial stewardship will theoretically have a lower impact in solid organ transplant recipients because of underling immunosuppression, widespread (but indicated) use of antimicrobial prophylaxis, and the need to administer antimicrobials promptly if there is concern for infection to prevent infection related morbidity and mortality.

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C. difficile is an important hospital-associated pathogen in solid organ transplant recipients. The incidence of CDI both inpatient and outpatient settings is increasing. Epidemics of severe disease in are more frequent. A hypervirulent strain has emerged. Optimal treatment recommendations are evolving but present data support using metronidazole for mild-to-moderate symptoms and vancomycin for severe disease (Table 3). To reduce the spread of C. difficile within healthcare setting, implement appropriate antimicrobial stewardship, hand hygiene, and environmental decontamination programs. 

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Table 1. Comparison of Stool Assays to Diagnose C. difficile Infection

Assay Advantages Disadvantages
Toxin enzyme ELISA High specificity, inexpensive, easy to perform, rapid Lower sensitivity, some assays detect only toxin A;
Cytotoxicity cell assay High specificity, high sensitivity Expensive, up to 72 hour wait for results, technically demanding
Glutamate dehydrongenase (GDH) EIA Inexpensive, results within 1 hour, high sensitivity Not specific as other bacteria also produce
Stool culture Most sensitive, provides isolates for strain typing Expensive, does not determine if isolate is toxigenic, ≥ 48 hours for results
PCR Rapid, high sensitivity, simple to perform Expensive, less experience


Table 2. CDI Severity and Associated Symptoms

Mild-to-moderate Severe Severe with complications
Mild to moderate diarrhea, mild to moderate abdominal pain, low grade fever Moderate to severe diarrhea, moderate to severe abdominal pain, leukocytosis >15,000 cells/mm3, and fever >38.5, peritoneal signs, acute renal failure, systemic toxicity ileus, toxic megacolon, refractory hypotension, leucosytosis >35,000 cells/mm3, or multiorgan failure


Table 3: General Recommendations for treatment of CDI

CDI Severity Treatment  
Mild-to-moderate Metronidazole 500mg PO TID x10-14d
Severe Vancomycin 125mg PO QID x 10-14d
Severe with complications Metronidazole

500mg IV TID


Oral vancomycin 125 mg to 500 mg qid (if tolerated)


Consider rectal vancomycin retention enemas 125 mg to 500 mg qid (especially if ileus is present)


Surgical consult


IVIG 250-500mg/kg IV x1

    Adapted from (26)


Bartlett JG.  Historical Perspectives on Studies of Clostridium difficile and C. difficile infection.  Clin Infect Dis 2008;46(Suppl 1):S4-S11.


Clostridium difficile Infection in Solid Organ Transplant Patients