Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 5) pps

Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 5) Recurrent CDAD Overall, ~15–30% of patients experience recurrences of CDAD, either as relapses caused by the original organism or as reinfections following treatment (Table 123-2). Recurrence rates are higher among patients ≥65 years old and among patients who remain in the hospital after the initial episode of CDAD. Patients who have a first recurrence of CDAD have a high rate of second recurrence (33–65%). In the first recurrence, re-treatment with metronidazole is comparable to treatment with vancomycin. Recurrent disease, once thought to be relatively mild, has been documented to pose a significant (11%) risk of serious complications (shock, megacolon, perforation, colectomy, or death within 30 days). There is no standard treatment for multiple recurrences, but long or repeated metronidazole courses should be avoided because of potential neurotoxicity. Approaches include the administration of vancomycin followed by the yeast Saccharomyces boulardii; the administration of vancomycin followed by synthetic fecal bacterial enema; and the intentional colonization of the patient with a nontoxigenic strain of C. difficile. None of these biotherapeutic approaches has been approved by the FDA for use in the United States. Other strategies include (1) the use of vancomycin in tapering doses or with pulse dosing every other day for 4–6 weeks and (2) sequential treatment with vancomycin (125 mg four times daily) followed by rifaximin (400 mg twice daily) for 14 days. IV immunoglobulin, which has also been used with some success, presumably provides antibodies to C. difficile toxins. Fulminant CDAD Fulminant (rapidly progressive and severe) CDAD presents the most difficult treatment challenge. Patients with fulminant disease often do not have diarrhea, and their illness mimics an acute surgical abdomen. Sepsis (hypotension, fever, tachycardia, leukocytosis) may result from severe CDAD. An acute abdomen (with or without toxic megacolon) may include signs of obstruction, ileus, colon-wall thickening, and ascites on abdominal CT, often with peripheral- blood leukocytosis (≥20,000 cells/µL). Whether or not the patient has diarrhea, the differential diagnosis of an acute abdomen, sepsis, or toxic megacolon should include CDAD if the patient has received antibiotics in the past 2 months. Cautious sigmoidoscopy or colonoscopy to visualize PMC and an abdominal CT examination are the best diagnostic tests in patients without diarrhea. Medical management of fulminant CDAD is suboptimal because of the difficulty of delivering metronidazole or vancomycin to the colon by the oral route in the presence of ileus. Vancomycin (given via nasogastric tube and by retention enema) plus IV metronidazole have been used in uncontrolled studies with some success, but surgical colectomy may be life-saving if there is no response to medical management. The incidence of fulminant CDAD requiring colectomy appears to be increasing in the evolving epidemic. Prognosis The mortality rate attributed to CDAD, previously found to be 0.6–3.5%, has reached 6.9% in recent outbreaks and is progressively higher with increasing age. Most patients recover, but recurrences are common. Prevention and Control Strategies for the prevention of CDAD are of two types: those aimed at preventing transmission of the organism to the patient and those aimed at reducing the risk of CDAD if the organism is transmitted. Transmission of C. difficile in clinical practice has been prevented by gloving of personnel, elimination of the use of contaminated electronic thermometers, and use of hypochlorite (bleach) solution for environmental decontamination of patients' rooms. Hand hygiene is critical; hand washing is recommended in CDAD outbreaks because alcohol hand gels are not sporicidal. CDAD outbreaks have been best controlled by restricting the use of specific antibiotics, such as clindamycin and second- and third- generation cephalosporins. Outbreaks of CDAD due to clindamycin-resistant strains have resolved promptly when clindamycin use was restricted Further Readings Aslam S et al: Treatment of Clostridium difficile– associated disease: Old therapies and new strategies. Lancet Infect Dis 5:549, 2005 [PMID: 16122678] Johnson S et al: Interruption of recurrent Clostridium difficile– associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 44:846, 2007 [PMID: 17304459] Kyne L et al: Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhea. Lancet 357:189, 2001 [PMID: 11213096] ——— et al: Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 342:390, 2000 Loo VG et al: A predominantly clonal multi- institutional outbreak of Clostridium difficile– associated diarrhea with high morbidity and mortality. N Engl J Med 353:2442, 2005 [PMID: 16322602] McDonald LC et al: Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996- 2003. Emerg Infect Dis 12:409, 2006 [PMID: 16704777] ——— et al: An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med 353:2433, 2005 McFarland LV: Alternative treatments for Clostridium difficile disease: What really works? J Med Microbiol 54:101, 2005 [PMID: 15673502] Pepin J et al: The management and outcomes of a first recurrence of Clostridium difficile associated disease in Quebec. Clin Infect Dis 42:758, 2006 [PMID: 16477549] Zar FA et al: A comparison of vanco mycin and metronidazole for the treatment of Clostridium difficile– associated diarrhea, stratified by disease severity. Clin Infect Dis 45:302, 2007 [PMID: 17599306] Bibliography Bartlett JG: Narrative review: The new epidemic of Clostridium difficile– associated enteric disease. Ann Intern Med 145:758, 2006 [PMID: 17116920] Kuijper EJ et al: Emergence of Clostridium difficile– associated disease in North America and Europe. Clin Microbiol Infect 12(Suppl 6):2, 2006 Musher D et al: Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 40:1586, 2005 [PMID: 15889354] Pepin J et al: Increasing risk of relapse after treatment of Clostridium difficile colitis in Québec, Canada. Clin Infect Dis 40:159 1, 2005 [PMID: 15889355] . Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 5) Recurrent CDAD Overall, ~15–30% of patients. of Clostridium difficile colitis with metronidazole. Clin Infect Dis 40:1586, 2005 [PMID: 15889354] Pepin J et al: Increasing risk of relapse after treatment of Clostridium difficile colitis. toxin A and protection against recurrent Clostridium difficile diarrhea. Lancet 357:189, 2001 [PMID: 11213096] ——— et al: Asymptomatic carriage of Clostridium difficile and serum levels