Pseudomembranous Colitis Surgery

Pseudomembranous colitis is an inflammatory disease of the colon. In some cases (5-19%), the disease is localized to the cecum and the proximal colon.

The antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile.[4] Colitis results from the bacterial production of large amount of toxins. The most important toxins are toxin A (enterotoxin) and toxin B (cytotoxin). One theory explains the variable severity of clinical disease through differential production rates of one toxin or the other by selected bacterial isolates. Most experts, however, believe that these variations are due to host factors.

The toxins bind to the mucosa, attack the membranes and the microfilaments of the mucosal cells, and subsequently result in cytoplasmic contraction, hemorrhage, inflammation, cellular necrosis, and protein loss. They also interfere with mucosal protein synthesis, stimulate granulocyte chemotaxis, and increase capillary permeability, intestinal myoelectric responses, and peristalsis. Intestinal tissue invasion by C difficile has been reported in fatal cases of pseudomembranous colitis in pediatric patients with hematologic malignancy.

Pseudomembranous colitis usually is associated with antibiotic use, which may alter the balance of normal gut flora and allow overgrowth of certain organisms.[4] Clindamycin, lincomycin, ampicillin, and cephalosporin have been implicated in most of the reported cases, but any antimicrobial agent (including antifungal, antiviral, and metronidazole) could incite the disease, regardless of the amount administered or the route of administration.

C difficile, a gram-positive, spore-forming, anaerobic bacillus, is isolated in almost all of these cases. Rare cases have been related to Staphylococcus aureus, Salmonella species, Clostridium perfringens, Yersinia species, Shigella species, Campylobacter species, cytomegalovirus, Entamoeba histolytica, and Listeria species.

Conditions other than antimicrobial administration could predispose to C difficile pseudomembranous colitis. Such conditions include bowel ischemia, recent bowel surgery, uremia, dietary change, change in bowel motility, malnutrition, chemotherapy, shock, and Hirschsprung disease.

The incidence of antibiotic-associated diarrhea ranges from 5% to 39%, depending on the antibiotic type. Pseudomembranous colitis complicates 10% of cases of antibiotic-associated diarrhea. C difficile is found in the stool of 15-25% of asymptomatic, antibiotic-treated, hospitalized adults. Similar numbers were found in debilitated patients and in patients who received one dose of prophylactic antibiotics before surgical procedure.

C difficile is an unusual component of healthy bowel flora. It is found in 3-5% of healthy adults; however, as many as 50% of infants and children harbor the bacteria and its toxins. Pseudomembranous colitis is a surprisingly rare disease in infants and young children—a population recognized as frequent asymptomatic colonizers. The low incidence of colitis in the pediatric population is attributed to the strength of the immune system. Antibodies to C difficile frequently are detected in infected young patients.

About 25% of human C difficile isolates are nontoxigenic. C difficile colitis is the fourth most common nosocomial disease reported to the Centers for Disease Control and Prevention. C difficile is one of the most frequently isolated enteric pathogens, second only to Campylobacter jejuni.[5]

High-risk populations[6] include elderly people, patients in the intensive care unit (ICU), people with uremia, people with burns, people undergoing abdominal surgery, women undergoing cesarean delivery, and patients with cancer. One suggestion is that these patients do not have greater susceptibility to the disease but are at heightened risk of nosocomial infection. C difficile can be transmitted nosocomially, via the hands of personnel or by contaminated objects. It can survive in spore form for as long as 5 months on hospital floors.

The overall mortality for pseudomembranous colitis is 2%. The mortality in untreated elderly or debilitated patients is 10-20%. Even with surgical intervention, mortality and morbidity in patients with toxic megacolon remain high (35% and 66%, respectively).[7]

Symptoms of pseudomembranous colitis may not begin until a few weeks after discontinuance of the antibiotic. They may range from loose stool in the mildest cases to toxic megacolon (fever, nausea, vomiting, and ileus)[8] and colonic perforation (rigid abdomen and rebound tenderness) in the most severe cases.

Symptoms include the following:

• Profuse, watery or mucoid, green, foul-smelling, liquid stool may contain small amounts of blood
• Cramping abdominal pain may occur
• The patient's temperature may reach 103-105°F (39.4-40.6ºC)
• Extraintestinal manifestations of oligoarthritis and iridocyclitis are extremely rare

One day to 6 weeks may elapse between the start of antibiotic therapy and the beginning of the clinical symptoms. In most cases, however, symptoms begin 3-9 days after the antibiotics are started.

In some cases (5-19%), the disease is localized to the cecum and the proximal colon. These patients may present with acute abdomen and localized rebound tenderness in the right lower quadrant but no diarrhea. With such a clinical presentation, considering this diagnosis and confirming it with stool studies (stool cytology results might be negative for C difficile toxins) and computed tomography (CT) may help avoid unnecessary surgery.

C difficile colitis should be suspected in infants and children with Hirschsprung disease when it is complicated by enterocolitis. These cases call for special attention because they often are associated with high risk.

Refractory C difficile colitis can be defined as disease that does not respond to vancomycin or metronidazole. Fulminant C difficile colitis can be defined as disease that progresses rapidly to cause systemic manifestation, including hypotension, renal failure, and anasarca. In practice, these two forms often overlap; their management is challenging, and their incidence is rising.

With these conditions, abdominal distention and tenderness may be present, and diarrhea may be absent or minimal as a consequence of ileus, which may obscure the diagnosis. Subtotal colectomy can be lifesaving, but the optimal timing is difficult to establish. Early surgical consultation when fulminant or refractory disease is suspected is highly recomended.[9]

Hypovolemic shock, dehydration, and electrolytes depletion may occur. Hypoproteinemia as a result of protein-losing enteropathy may occur in patients with prolonged diarrhea. Cecal perforation, toxic megacolon,[8]  hemorrhage, and sepsis also can occur.

Laboratory studies to be considered include the following:

• Complete blood count (CBC) - This will reveal leukocytosis, with the white blood cell (WBC) count in the range of 10,000-50,000/μL
• Blood chemistry - Hypoalbuminemia is common
• Fecal leukocytes - Positive tests for fecal leukocytes (3-5 leukocytes per high-power field [HPF]) excludes benign diarrhea; however, a negative result does not exclude colitis
• Stool culture - Culture of C difficile is relatively demanding, with low predictive value because of the large number of asymptomatic carriers; many laboratories do not perform this test
• Stool assay for C difficile toxins (mostly toxin B) - This test requires 2 days and is considered positive when cultured cells undergo cytopathic changes when exposed to stool, with the result then confirmed by neutralizing these toxins with specific antitoxins; although this is the criterion standard test (sensitivity is 95% in patients with antibiotic-induced diarrhea and increases with the severity of the colitis), results are negative in 5-10% of patients with endoscopic evidence of pseudomembranous colitis
• Enzyme-linked immunoabsorbent assay (ELISA) for toxin A - This test is less expensive than stool assay for C difficile toxins and is completed in 2.5 hours; however, sensitivity (75-85%) is lower
• Latex agglutination test - This test has poor sensitivity and specificity
• Polymerase chain reaction (PCR) - The PCR test is expensive but fast and highly sensitive and specific; it is currently used only as a research tool in laboratories for detecting C difficile toxin genes A and B in fecal specimens ^[10]
• Glutamate dehydrogenase - This enzyme (also referred to as the common antigen ^[10] ) is expressed at high levels by all strains of C difficile; ELISA screening tests are highly sensitive, simple, and cost-effective for detecting it; although none of these screening tests specifically identify toxigenic strains, since the enzyme is produced by toxigenic and nontoxigenic strains, they have negative predictive values of roughly 99%, which supports their value for ruling specimens negative for C difficile ^[10]

Plain abdominal radiography may show mucosal edema and abnormal haustral pattern (see the image below). Ileus pattern was described in 28% of the patients. It is useful for ruling out toxic megacolon or perforation.

Frontal abdominal radiograph in a patient with proved pseudomembranous colitis. Note the nodular haustral thickening, most pronounced in the transverse colon.

Air contrast barium enema study can outline the mucosal abnormalities further; however, these are late and nonspecific findings. This procedure is not recommended, because it carries the risk of perforation and may precipitate toxic megacolon.

Computed tomography (CT) may show distention and diffuse and focal thickening of the wall of the colon, along with pericolonic inflammation.

Indium-labeled leukocyte scans will show nonspecific inflammation of the colonic mucosa.

Pseudomembranous colitis is uncommon in infants and young children. They commonly harbor C difficile and its toxins in their stool, which makes it difficult to diagnose the disease in this age group. A therapeutic trial with vancomycin may be the only way to confirm the clinical significance of the positive toxins in the stool.

Rigid proctosigmoidoscopy is diagnostic in 77% of patients. Endoscopic visualization of the pseudomembranes characteristic of the disease (see the images below) is the most rapid and definitive diagnostic method. When the pseudomembranes are manipulated, ulcerated mucosa is uncovered. In early stages of the disease, lesions may be confused with Crohn disease, Behçet disease, and viral colitis.

Colonic pseudomembranes of pseudomembranous colitis. Photographs courtesy of Eric M. Osgard, MD.

Endoscopic visualization of pseudomembranous colitis, a characteristic manifestation of full-blown Clostridium difficile colitis. Classic pseudomembranes are visible as raised yellow plaques, which range from 2-10 mm in diameter and are scattered over the colorectal mucosa. Courtesy of Gregory Ginsberg, MD, University of Pennsylvania.

Flexible sigmoidoscopy is diagnostic in 91% of the patients.

Colonoscopy may be required in 10% of the cases where the disease is localized to the cecum or transverse colon with rectal sparing. It is a hazardous procedure in patients with toxic megacolon.

Gross pathologic analysis reveals raised exudative plaques 2-5 mm in size, the coalescence of which gives rise to yellowish pseudomembranes lining the colonic mucosa (see the images below).

Gross pathology specimen from a case of pseudomembranous colitis revealing characteristic yellowish plaques.

Gross pathology specimen from a case of pseudomembranous colitis, again demonstrating characteristic yellowish plaques.

Pseudomembranous colitis usually is associated with antibiotic use. In mild or moderate cases, supportive therapy alone is sufficient. Such therapy includes the following:

• Discontinuing or changing the offending antibiotics
• Avoiding narcotics and antidiarrheal agents
• Maintaining fluid and electrolyte intake
• Employing enteric isolation

In fulminant or intractable cases, hospitalization for intravenous (IV) hydration will be necessary. Two thirds of patients with toxic megacolon require surgical intervention.[8]

Therapeutic strategies to inhibit toxin A–induced colitis are being tested. 5-Aminosalicylic acid (ASA) is an area of interest.[11] In an animal model, APAZA, a compound consisting of a molecule of 5-ASA linked to a molecule of 4-aminophenylacetic acid by an azo bond, was found to significantly inhibit toxin A–induced myeloperoxidase activity, luminal fluid accumulation, and structural damage to the colon when administered for 5 days in drinking water.[12] Sulfasalazine has been reported to have similar effects, as has resiniferatoxin.[13]

Clinical practice guidelines on the management of C difficile infection have been published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA).[14, 15] ; the American Society of Colon and Rectal Surgeons[16] ; and the World Society of Emergency Surgery (WSES).[17]  (See Guidelines.) 

In mild or moderate cases of pseudomembranous colitis, supportive therapy alone is sufficient. This includes discontinuing or changing the offending antibiotics, avoiding narcotics and antidiarrheal agents, maintaining fluid and electrolyte intake, and enteric isolation. Most patients—75% of symptomatic patients and 25% of patients with colitis—will experience complete recovery within 10 days. In fulminant or intractable cases, hospitalization for IV hydration will be necessary.

Oral treatment with antimicrobial agents effective against C difficile is the preferred treatment. No reliable parenteral treatment for pseudomembranous colitis exists.

In elderly patients and in severely ill patients, empiric antibiotic treatment should be started when the diagnosis is suspected. In severe cases, in cases where supportive therapy fails, and in cases where the offending antibiotic cannot be discontinued, a short (7-10 d) course of specific antibiotic therapy should be administered along with the supportive therapy, and the offending antibiotic should be changed to another appropriate agent when possible. Recurrent diseases respond well to repeat treatment with vancomycin or fidaxomicin.

In cases with multiple recurrences, a few therapeutic regimens have been suggested. In one, a long (4-6 wk) course of oral antibiotic is administered, followed by gradual tapering, or pulsing, of vancomycin (125 mg q6hr for 1 week, 125 mg q12hr for 1 week, 125 mg q24hr for 1 week, or 125 mg q48hr for 1 week; followed by 125 mg q72hr for 2 weeks). Another suggested regimen is administering 5-7 days of intermittent antibiotic treatment periods alternating with periods off antibiotics.

Treatment with a combination of vancomycin and rifampin was reported to be successful in some cases.

Antimicrobial therapy

Vancomycin

Vancomycin has been the most reliable treatment of the disease (90-100% response rate in adult men). The risk of developing resistant bacterial strains should be considered. Because oral vancomycin is absorbed poorly, the high stool concentration that is required for the treatment of C difficile can be achieved without systemic side effects. The recommended dosage is 125 mg orally (PO) every 6 hours for 7-14 days for adults and 500 mg/1.73 m2 every 6 hours for infants. It can be used as a therapeutic trial in infants to establish the diagnosis.

Vancomycin 500 mg every 6 hours has been the treatment of choice for staphylococcal enterocolitis, typhlitis, and severely ill patients with C difficile colitis. In patients who do not improve promptly, reassessment is warranted to make sure that no other diagnosis has been missed. If the diagnosis remains the same, vancomycin may be switched to metronidazole. When parenteral therapy is the only possible treatment due to paralytic ileus, using both vancomycin and metronidazole IV, supplemented by vancomycin 500 mg every 6 hours via nasogastric tube or by enema, has been recommended.

The updated IDSA-SHEA guidelines published in 2021 favored fidaxomicin over vancomycin for initial and recurrent episodes of C difficile infection but noted that the latter agent remains an acceptable alternative.[14]

Metronidazole

Metronidazole is an inexpensive, effective treatment for pseudomembranous colitis. It has a response rate of 86-92% when used orally in adult men. It is equal to vancomycin in relapse rate with a higher side-effect profile. An dosage of 250 mg PO every 6 hours for 7-10 days has been recommended. It is not recommended for children or for women during pregnancy. The 2021 ASCRS guidelines stated that metronidazole alone is no longer considered appropriate first-line treatment for C difficile infection.[16]

Fidaxomicin

Fidaxomicin is a macrolide antibiotic that is bactericidal against C difficile in vitro. The recommended dosage is 200 mg PO every 12 hours for 10 days. The risk for recurrence is lower after fidaxomicin therapy than after vancomycin therapy.[18]  The 2021 IDSA-SHEA guidelines favor fidaxomicin over vancomycin.[14]

Fidaxomicin was found to be superior to vancomycin for patients with cancer who have C difficile. In a multicenter study including 1105 subjects with C difficile–associated diarrhea, 183 of whom had solid tumors or hematologic malignancies, fidaxomicin treatment was superior to vancomycin treatment in cancer patients, resulting in higher cure and sustained response rates for diarrhea, shorter time to resolution of diarrhea (TTROD), and fewer recurrences.[18]

Cure rates for diarrhea were lower overall in cancer patients than in others (79.2% vs 88.6%).[18] Whereas cure rates for noncancer patients were approximately the same with fidaxomicin as with vancomycin (88.5% vs 88.7%), those for cancer patients were higher with fidaxomicin than with vancomycin (85.1% vs 74.0%), though the difference was not statistically significant.

In a systematic review and meta-analysis (10 studies, mostly of poorer quality) comparing fidaxomicin and vancomycin/metronidazole regimens in the treatment of C difficile infection,[19] Dai et al did not find significant differences in treatment outcomes (eg, clinical cure, sustained cure, recurrence, and all-cause mortality); however, they did find a significantly higher risk of treatment failure with fidaxomicin.

Bacitracin

The recommended dosage of bacitracin is 500-1000 mg PO every 6 hours for 7-19 days. As alternative therapy for symptomatic relief, it is less effective than vancomycin in clearing C difficile from stool. An oral form is not available, but the parenteral form may be administered orally.

Teicoplanin

Teicoplanin is not available in the United States but is widely used in Europe, Asia, and South America. It compares favorably with vancomycin, with a longer half-life that allows less frequent dosing. The recommended dosage is 100 mg PO every 12 hours.

Bezlotuxumab

Studies suggested that the monoclonal antibody bezlotoxumab may be effective for the prevention of recurrent C difficile infection.[20]  The 2021 IDSA-SHEA guidelines suggested that for patients with a recurrent episode of C difficile infection within the preceding 6 months, bezlotoxumab may be given as a cointervention along with standard-of-care antibiotics.[14]

Other medical therapies

Cholestyramine

Cholestyramine contains anion exchange binding resins, which exert their beneficial effect in pseudomembranous colitis by binding C difficile toxins and eliminating these toxins from the colonic lumen. It is used in patients with mild disease and in relapses. The response rate is variable and low in general. The recommended dose is 4 g PO every 6 hours. Obstipation is the most common adverse effect. It should not be used simultaneously with vancomycin.

Intravenous immunoglobulin

It is known that individuals with high antitoxin immunoglobulin G (IgG) titers are more likely to recover quickly or be asymptomatic carriers, whereas patients with low titers are reported to have more severe, more prolonged, or recurrent disease. Because more than 50% of the population has detectable serum IgG antibodies to C difficile toxins A and B, pooled normal IV immunoglobulin (IVIg) has toxin-neutralizing activity. Thus, IVIg (400 mg/kg) may be a worthwhile intervention in fulminant or refractory disease.[9, 21, 22]

Antidiarrheal agents

Antiperistaltic drugs should be avoided. They may provide temporary symptomatic relief, but they may protract the disease by prolonging the mucosal exposure to the bacterial toxins, resulting in more severe colonic damage. Postoperative narcotics may play a similar role. Diphenoxylate-atropine is especially dangerous in infants.

Restoration of normal flora

In patients with multiple relapses, attempts have been made to recolonize the colon by introducing organisms to suppress C difficile. Some of the results were encouraging. Oral Lactobacillus GG has been used. Oral nonpathogenic yeast, such as Saccharomycesboulardii, also has been used effectively in treatment of multiple relapses.

Fecal microbiota transplantation (FMT; given as an enema or through a nasogastric tube) from selected healthy donors, though it carries the risk of disease transmission, holds considerable promise as a therapy for recurrent or refractory cases.[23, 24]  A randomized study by Cammarota et al found this therapy to be significantly better than vancomycin for treating recurrent infection.[25]  Mironova et al, in a study of 106 patients with severe and fulminant C difficile infection, found that FMT may decrease mortality in this setting.[26]

Steroids

Corticosteroid therapy was reported to be safe and effective in the treatment of severe cases but is not widely recommended.

Nontoxigenic clostridial spores

Gerding et al studied oral administration of spores of nontoxigenic C difficile (NTCD) strain M3 (NTCD-M3) to 173 adult patients with C difficile infection who had successfully completed treatment with metronidazole, oral vancomycin, or both with the goal of preventing recurrent infection.[27]  Oral NTCD-M3 was well tolerated and apparently safe, and it was associated with a significant decrease in recurrent C difficile infection.

Two thirds of patients with toxic megacolon require surgical intervention.[8]  Research has been focusing on identification of objective parameters that can be used to determine which patients are most likely to benefit from surgery.

Diverting ileostomy or resection of diseased bowel (subtotal colectomy) was necessary treatment before antibiotic therapy was available. With the development of antibiotic therapy, such procedures came to be used only as a life-saving measure, such as in cases of perforated cecum or toxic megacolon.[28]

Colostomy or ileostomy is used rarely for direct instillation of antibiotic into the colon lumen in patients with paralytic ileus. Pseudomembranous colitis could be the cause of early dysfunction of the colostomy. Ileal involvement in the disease has been reported as a complication of ileostomy. These treatments have been shown to reduce morbidity and preserve the colon.[29]

Early subtotal colectomy is advocated by some surgeons in fulminant toxic cases that do not respond after a week of intensive medical therapy because the risk of perforation increases after 7 days of ineffective medical therapy.

A study by Ahmed et al that assessed total abdominal colectomy for toxic megacolon resulting from C difficile colitis found that mortality was 21% in those who underwent colectomy early (before the development of septic shock), compared with 45% who underwent colectomy late (after the development of septic shock).[30]

A 2017 multicenter study from the Eastern Association for the Study of Traum (EAST) compared loop ileostomy with total colectomy for the treatment of C difficile–associated disease.[31]  The two groups were not significantly different with respect to preoperative patient conditions, preprocedure predictors of mortality, or APACHE score. Overall mortality was 32%, with a 75% rate of postoperative complications. Adjusted mortality was significantly lower in the ileostomy group (17.2%) than in the total colectomy group (39.7%).

A 2020 systematic review and meta-analysis (N = 3683; five studies) by Shellito et al evaluated diverting loop ileostomy with colonic lavage (n = 733) as an alternative to total abdominal colectomy (n = 2950) for fulminant C difficile infection.[32]  The findings suggested that loop ileostomy may be a viable surgical alternative to total colectomy in this setting, with similar mortality, though further study is required to determine which specific patient characteristics might warrant routine use of the former.

For prevention, use antibiotics prudently. Wash hands, and use examination gloves routinely. Clean potentially contaminated surfaces. Use glutaraldehyde disinfection of instruments that come into contact with gastrointestinal secretions. Enteric isolation of patients at risk is recommended. Treatment of asymptomatic carriers is not recommended, because treatment may prolong carriage, which usually resolves spontaneously.

Passive immunization, which has been effective in animals, may be potentially useful in protecting patients with a high risk of acquiring the disease. Immunologic studies of toxin A, toxin B, and other virulence factors have led to toxoids that have been used for the production of antibodies that might be used to generate a vaccine in this group of patients.

Many patients remain asymptomatic carriers of C difficile, and most of them never relapse.

Between 10% and 20% of all treated patients will have a relapse, regardless of the therapeutic agent used. This could be due either to germination of spores or reinfection. Response to retreatment with vancomycin usually is favorable. In patients with multiple symptomatic relapses, vancomycin pulsing is recommended (125 mg q6hr for 1 week, 125 mg q12hr for 1 week, 125 mg q24hr for 1 week, or 125 mg q48hr for 1 week; followed by 125 mg q72hr for 2 weeks).

In 2021, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) published a focused update to their 2018 clinical practice guidelines on treatment of Clostridioides (Clostridium) difficile infection (CDI).[14, 15]  Recommendations included the following:

• In patients with a first C  difficile infection (CDI) episode, fidaxomicin is recommended instead of a standard course of vancomycin
• In those with recurrent CDI episodes, fidaxomicin (standard or extended-pulsed regimen), rather than a standard course of vancomycin, is recommended
• In patients who experience a recurrent CDI episode within the preceding 6 months, it is recommended to use bezlotoxumab as a co-intervention in combination with standard-of-care (SOC) antibiotics, rather than SOC antibiotics only

In 2021, the American Society of Colon and Rectal Surgeons (ASCRS) published clinical practice guidelines on the management of CDI.[16] Recommendations included the following:

• Oral vancomycin or fidaxomicin is first-line treatment for an initial CDI
• Metronidazole alone is no longer considered appropriate first-line treatment for CDI
• Surgery for C difficile colitis should be reserved for patients with colonic perforation or severe colitis who do not improve with medical therapy
• Subtotal colectomy with end ileostomy is recommended for severe-complicated or fulminant C difficile colitis
• A diverting loop ileostomy with antegrade colonic lavage may be an alternative to subtotal colectomy for the treatment of severe-complicated or fulminant CDI
• A prolonged course of vancomycin, adding bezlotoxumab or using fidaxomicin, is an acceptable therapy for recurrent or refractory CDI in stable patients
• Patients with recurrent or refractory CDI should be considered for fecal bacteriotherapy if conventional measures have failed

In February 2019, the World Society of Emergency Surgery (WSES) published the following guidelines on diagnosis and treatment of CDI in surgical patients.[17]

Diagnosis

Diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests. Stool testing should only be performed on diarrheal stools from at-risk patients with clinically significant diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation.

For patients with ileus who may be unable to produce stool specimens, polymerase chain reaction (PCR) testing of perirectal swabs is an acceptable alternative to stool specimen analysis.

Nucleic acid amplification testing (NAAT) for C difficile toxin genes appears to be sensitive and specific and may be used as a standard diagnostic test for CDI. NAAT may be performed as a single-step algorithm or included in a two-step algorithm starting with toxin enzyme immunoassay (EIA).

Glutamate dehydrogenase (GDH) testing is sensitive but does not differentiate between toxigenic and nontoxigenic strains. It may be used in association with toxin A/B EIA testing. Algorithms including screening with EIA for GDH followed by toxin assay may be suggested.

EIA for toxin A/B is fast, inexpensive, and highly specific but is relatively insensitive and is not recommended alone.

C difficile culture is relatively slow but sensitive and is rarely performed as a routine diagnostic test. It is recommended for subsequent epidemiologic typing and characterization of strains.

Repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with (a) ongoing clinical suspicion during an epidemic situation or (b) high clinical suspicion during endemic situations.

Computed tomography (CT) is suggested for patients with clinical manifestations of severe-to-complicated C difficile colitis; however, it is not sensitive enough for screening.

Ultrasonography (US) may be useful in critically ill patients suspected of having pseudomembranous colitis who cannot be transported to the CT suite.

Flexible sigmoidoscopy may be helpful in diagnosing C difficile colitis when there is a high level of clinical suspicion for CDI.

Antibiotic therapy

Unnecessary antibiotics should be discontinued if CDI is suspected. Unnecessary proton pump inhibitors (PPIs) should be discontinued in patients at high risk for CDI.

Empirical antibiotic therapy should be avoided unless CDI is strongly suspected. In such cases, empirical therapy for CDI should be considered while test results are awaited.

Oral metronidazole should be limited to treatment of an initial episode of mild-to-moderate CDI. Oral vancomycin is recommended for treatment of mild-to-moderate disease unresponsive to metronidazole. Repeated or prolonged courses of metronidazole should be avoided. Oral vancomycin and fidaxomicin are both recommended for treatment of severe CDI.

When oral antibiotics cannot reach the colon, vancomycin may be administered as a retention enema via a large rectal tube or catheter.

Fidaxomicin may be used to treat CDI, especially in patients at higher risk for recurrence (eg, elderly patients or those receiving concomitant antibiotics).

Surgical management

Patients with severe CDI who progress to systemic toxicity should undergo early surgical consultation and should be evaluated for potential surgical intervention.

For patients with fulminant colitis, total colectomy should be considered. However, diverting loop ileostomy with colonic lavage is a useful alternative.

Fulminant colitis should be treated with high-dose vancomycin (500 mg q6hr), orally or via enema or both, in combination with intravenous (IV) metronidazole (500 mg q8hr).

Supportive care

Early detection of shock and aggressive management of organ dysfunction are essential for improved outcomes in fulminant colitis. Supportive measures (eg, IV fluid resuscitation, albumin supplementation, and electrolyte replacement) should be provided to all patients with severe CDI.

Recurrent CDI

The first recurrence of CDI may be treated with vancomycin (particularly if metronidazole was used for the initial episode) or fidaxomicin. Antibiotic options for further recurrences include oral vancomycin in a tapered and pulsed regimen.

Probiotics

Limited direct evidence supports the use of probiotics in managing a first episode of CDI as an adjunct to antibiotics for immunocompetent patients.

Prophylactic probiotics may be considered for inpatients receiving antibiotics during a high-risk period before the disease develops. Probiotics should be not used in immunocompromised patients.

Probiotics for prevention of recurrent CDI may be an effective adjunct to standard antibiotic treatment (vancomycin) in patients with at least one prior episode of CDI.

Fecal microbiota transplantation

Fecal microbiota transplantation (FMT) may be an effective option for patients with multiple recurrences of CDI in whom appropriate antibiotic treatments have failed.

Monoclonal antibodies

Coadjuvant monoclonal antibody (bezlotoxumab) therapy may prevent CDI recurrences, particularly in patients who have CDI due to the 027 epidemic strain, are immunocompromised, or have severe CDI.

Intravenous immunoglobulin

IV immunoglobulin (IVIG) should be used only as adjunctive therapy in patients with multiple recurrences or fulminant CDI.

Enteral nutrition

Tube feeding patients should be clinically assessed due to their risk for developing CDI.

Antimotility agents

The use of antiperistaltic agents to treat CDI is discouraged. If such agents are used to control persistent symptoms, they must always be accompanied by medical therapy.