Pseudomembranous Colitis Surgery Treatment & Management
- Author: Said Fadi Yassin, MD; Chief Editor: John Geibel, MD, DSc, MSc, MA more...
Pseudomembranous colitis usually is associated with antibiotic use. In mild or moderate cases, supportive therapy alone is sufficient. This includes discontinuing or changing the offending antibiotics, avoiding narcotics and antidiarrheal agents, maintaining fluid and electrolyte intake, and 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.
Therapeutic strategies to inhibit toxin A–induced colitis are being tested. APAZA, a new compound consisting of a molecule of 5-aminosalicylic acid linked to a molecule of 4-aminophenylacetic acid by an azo bond, has been 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. Sulfasalazine has been reported to have similar effects.
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, empirical 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 days) 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.
In cases with multiple recurrences, a few suggested therapeutic regimens exist. A long (4-6 weeks) course of oral antibiotic may be 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.
Vancomycin is 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 therapeutic trial in infants to establish the diagnosis.
Vancomycin 500 mg every 6 hours is 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 should 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, is recommended.
Metronidazole is an inexpensive, effective treatment for pseudomembranous colitis. It is the preferred first line of treatment, with a response rate of 86-92% when used orally in adult men. It is equal to vancomycin in relapse rate with higher side effect profile. An dosage of 250 mg PO every 6 hours for 7-10 days is recommended. It is not recommended for children or for women during pregnancy.
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.
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.
Cure rates for diarrhea were lower overall in cancer patients than in others (79.2% vs 88.6%). 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.
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 is not available in the United States. It compares favorably with vancomycin, with a longer half-life that allows less frequent dosage. The recommended dosage is 100 mg PO every 12 hours.
Other medical therapies
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.
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, 12, 13]
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 (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. A randomized study by Cammarota et al found this therapy to be significantly better than vancomycin for treating recurrent infection.
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. 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.
Diverting ileostomy or resection of diseased bowel (subtotal colectomy) was necessary treatment before antibiotic therapy was available. This treatment currently is used only as a life-saving measure, such as in cases of perforated cecum or toxic megacolon.
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.
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. Research groups have been trying to identify objective parameters that can be used to determine which patients are most likely to benefit from surgery.
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, hemorrhage, and sepsis also can occur.
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).
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