Pseudomembranous Colitis Surgery Treatment & Management

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).