Clostridium difficile-Associated Diarrhea and Colitis
2001; Elsevier BV; Volume: 76; Issue: 7 Linguagem: Inglês
10.4065/76.7.725
ISSN1942-5546
AutoresSaid Fadi Yassin, Tonia M. Young‐Fadok, Nizar N. Zein, Darrell S. Pardi,
Tópico(s)Gastrointestinal motility and disorders
ResumoClostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea and colitis, typically after the use of broad-spectrum antibiotics. The clinical presentation ranges from self-limited diarrhea to fulminant colitis and toxic megacolon. The incidence of this disease is increasing, resulting in major medical and economic consequences. Although most cases respond quickly to medical treatment, C difficile colitis may be serious, especially if diagnosis and treatment are delayed. Recurrent disease represents a particularly challenging problem. Prevention is best accomplished by limiting the use of broad-spectrum antibiotics and following good hygienic techniques and universal precautions to limit the transmission of bacteria. A high index of suspicion results in early diagnosis and treatment and potentially reduces the incidence of complications. Clostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea and colitis, typically after the use of broad-spectrum antibiotics. The clinical presentation ranges from self-limited diarrhea to fulminant colitis and toxic megacolon. The incidence of this disease is increasing, resulting in major medical and economic consequences. Although most cases respond quickly to medical treatment, C difficile colitis may be serious, especially if diagnosis and treatment are delayed. Recurrent disease represents a particularly challenging problem. Prevention is best accomplished by limiting the use of broad-spectrum antibiotics and following good hygienic techniques and universal precautions to limit the transmission of bacteria. A high index of suspicion results in early diagnosis and treatment and potentially reduces the incidence of complications. During the past century, Clostridium difficile infection has changed from an often fatal postoperative event to primarily a nosocomial disease associated with antibiotic use. Because of widespread antibiotic use, C difficile–associated diarrhea (CDAD) has become a common problem with pronounced medical and economic effects. This is particularly important for surgeons because the most frequent indication for antibiotic use is perioperative prophylaxis and surgical patients comprise 55% to 75% of all patients with CDAD.1Jobe BA Grasley A Deveney KE Deveney CW Sheppard BC Clostridium difficile colitis: an increasing hospital-acquired illness.Am J Surg. 1995; 169: 480-483Abstract Full Text PDF PubMed Scopus (164) Google Scholar, 2Gerding DN Olson MM Peterson LR et al.Clostridium difficile-associated diarrhea and colitis in adults: a prospective case-controlled epidemiologic study.Arch Intern Med. 1986; 146: 95-100Crossref PubMed Scopus (317) Google Scholar The overall incidence is increasing,1Jobe BA Grasley A Deveney KE Deveney CW Sheppard BC Clostridium difficile colitis: an increasing hospital-acquired illness.Am J Surg. 1995; 169: 480-483Abstract Full Text PDF PubMed Scopus (164) Google Scholar and C difficile now is one of the most frequently implicated enteric pathogens (second only to Campylobacter jejuni) and the fourth most common nosocomial disease reported to the Centers for Disease Control and Prevention.3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar This article summarizes the existing literature on C difficile disease. We performed a MEDLINE search to identify articles with the key words Clostridium difficile, pseudomembranous enterocolitis, or antibiotic-associated diarrhea (as a text word). The resultant articles were initially limited to review articles of human studies in the English language between 1990 and 2001. The resultant citations were reviewed for appropriate articles. These references were then supplemented with original articles as identified in the bibliographies of the selected citations, including references before 1990. The first case of pseudomembranous colitis (PMC) was reported in 1893 as diphtheritic colitis,4Finney JMT Gastroenterostomy for cicatrizing ulcer of the pylorus.Johns Hopkins Hosp Bull. 1893; 4: 53-55Google Scholar and the C difficile organism was first described in 1935.5Hall IC O'Toole E Intestinal flora in new-born infants.Am J Dis Child. 1935; 49: 390-402Crossref Google Scholar Early cases of PMC were thought to be due to Staphylococcus aureus, and it was not until the 1970s that C difficile was implicated as a causative factor.6Larson HE Price AB Honour P Borriello SP Clostridium difficile and the aetiology of pseudomembranous colitis.Lancet. 1978; 1: 1063-1066Abstract PubMed Google Scholar, 7Tedesco FJ Stanley RJ Alpers DH Diagnostic features of clindamycin-associated pseudomembranous colitis.N Engl J Med. 1974; 290: 841-843Crossref PubMed Scopus (75) Google Scholar Although PMC was described before the antibiotic era, currently the vast majority of cases are associated with antibiotics, which alter the balance of normal gut flora and allow overgrowth of C difficile.3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar, 8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar Clindamycin, lincomycin, ampicillin, or the cephalosporins have been implicated in most reported cases, but almost any antimicrobial agent (including antifungals, antivirals, vancomycin, and metronidazole) can incite the disease.9Bingley PJ Harding GM Clostridium difficile colitis following treatment with metronidazole and vancomycin.Postgrad Med J. 1987; 63: 993-994Crossref PubMed Scopus (32) Google Scholar, 10Silva J Fekety R Werk C et al.Inciting and etiologic agents of colitis.Rev Infect Dis. 1984; 6: S214-S221Crossref PubMed Google Scholar, 11Colarian J Clostridium difficile colitis following antiviral therapy in the acquired immunodeficiency syndrome [letter].Am J Med. 1988; 84: 1081Abstract Full Text PDF PubMed Scopus (28) Google Scholar However, the aminoglycosides, erythromycin, trimethoprim-sulfamethoxazole, and the fluoroquinolones appear less likely to be causes.8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 10Silva J Fekety R Werk C et al.Inciting and etiologic agents of colitis.Rev Infect Dis. 1984; 6: S214-S221Crossref PubMed Google Scholar Factors other than antimicrobial use that can predispose to CDAD include bowel ischemia, recent bowel surgery, uremia, malnutrition, chemotherapy, shock, and possibly Hirschsprung disease.8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 12Zimmerman RK Risk factors for Clostridium difficile cytotoxin-positive diarrhea after control for horizontal transmission.Infect Control Hosp Epidemiol. 1991; 12: 96-100Crossref PubMed Scopus (28) Google Scholar, 13Cudmore MA Silva Jr, J Fekety R Liepman MK Kim KH Clostridium difficile colitis associated with cancer chemotherapy.Arch Intern Med. 1982; 142: 333-335PubMed Google Scholar, 14Brearly S Armstrong GR Nairn R et al.Pseudomembranous colitis: a lethal complication of Hirschsprung's disease unrelated to antibiotic usage.J Pediatr Surg. 1987; 22: 257-259Abstract Full Text PDF PubMed Scopus (40) Google Scholar The clinical spectrum of C difficile includes an asymptomatic carrier state, diarrhea without colitis, and variable degrees of colitis with or without pseudomembranes. C difficile carriage is uncommon in healthy adults (1%-3%) but is common in debilitated patients and antibiotic-treated hospitalized adults (15%-25%), including those who received 1 dose of antibiotic before surgery.2Gerding DN Olson MM Peterson LR et al.Clostridium difficile-associated diarrhea and colitis in adults: a prospective case-controlled epidemiologic study.Arch Intern Med. 1986; 146: 95-100Crossref PubMed Scopus (317) Google Scholar, 8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 12Zimmerman RK Risk factors for Clostridium difficile cytotoxin-positive diarrhea after control for horizontal transmission.Infect Control Hosp Epidemiol. 1991; 12: 96-100Crossref PubMed Scopus (28) Google Scholar, 15Privitera G Scarpellini P Ortisi G Nicastro G Nicolin R de Lalla F Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery.Antimicrob Agents Chemother. 1991; 35: 208-210Crossref PubMed Scopus (133) Google Scholar, 16McFarland L Surawicz CM Stamm WE Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients.J Infect Dis. 1990; 162: 678-684Crossref PubMed Scopus (379) Google Scholar, 17Thomas DR Bennett RG Laughon BE Greenough III, WB Bartlett JG Postantibiotic colonization with Clostridium difficile in nursing home patients.J Am Geriatr Soc. 1990; 38: 415-420Crossref PubMed Scopus (56) Google Scholar Up to 50% of infants and children harbor the bacteria.18Bacon AE Fekety R Schaberg DR Faix RG Epidemiology of Clostridium difficile colonization in newborns: results using a bacteriophage and bacteriocin typing system.J Infect Dis. 1988; 158: 349-354Crossref PubMed Scopus (44) Google Scholar The incidence of CDAD in ambulatory adults has been estimated at 7 to 12 cases per 100,000 person-years.19Hirschhorn LR Trnka Y Onderdonk A Lee ML Platt R Epidemiology of community-acquired Clostridium difficile-associated diarrhea.J Infect Dis. 1994; 169: 127-133Crossref PubMed Scopus (205) Google Scholar, 20Levy DG Stergachis A McFarland LV et al.Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.Clin Ther. 2000; 22: 91-102Abstract Full Text PDF PubMed Scopus (72) Google Scholar The incidence of antibiotic-associated diarrhea (AAD) varies from 5% to 39% depending on the antibiotic used,8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar and most cases in outpatients are due to the antibiotic and not C difficile.21Bartlett JG Antibiotic-associated diarrhea.Clin Infect Dis. 1992; 15: 573-581Crossref PubMed Scopus (366) Google Scholar However, most hospital-based outbreaks of AAD are likely due to C difficile.8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar Pseudomembranous colitis occurs in only 10% of patients with AAD.8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 22Bartlett JG Clostridium difficile: clinical considerations.Rev Infect Dis. 1990; 12: S243-S251Crossref PubMed Scopus (184) Google Scholar Pseudomembranous colitis is rare in infants and young children, perhaps because of a higher prevalence of antibodies to C difficile in younger compared to older subjects18Bacon AE Fekety R Schaberg DR Faix RG Epidemiology of Clostridium difficile colonization in newborns: results using a bacteriophage and bacteriocin typing system.J Infect Dis. 1988; 158: 349-354Crossref PubMed Scopus (44) Google Scholar, 22Bartlett JG Clostridium difficile: clinical considerations.Rev Infect Dis. 1990; 12: S243-S251Crossref PubMed Scopus (184) Google Scholar or to immature toxin receptors on colonocytes in infants.23Cleary RK Clostridium difficile-associated diarrhea and colitis: clinical manifestations, diagnosis, and treatment.Dis Colon Rectum. 1998; 41: 1435-1449Crossref PubMed Scopus (94) Google Scholar Populations at high risk for CDAD include elderly persons; patients with uremia, burns, or abdominal surgery or cesarean section; and cancer patients or those in the intensive care unit. Whether these groups have more exposure to nosocomial infections or are more susceptible to CDAD as a result of their illness is unknown.16McFarland L Surawicz CM Stamm WE Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients.J Infect Dis. 1990; 162: 678-684Crossref PubMed Scopus (379) Google Scholar Typically, CDAD presents within 1 to 2 weeks after an antibiotic has been instituted, although presentation varies from 1 day to 6 weeks.24Tedesco FJ Pseudomembranous colitis: pathogenesis and therapy.Med Clin North Am. 1982; 66: 655-664PubMed Google Scholar The disease usually presents with profuse watery or mucoid diarrhea that may contain blood, abdominal pain, and low-grade fever, although symptoms range from only loose stools in the mildest cases to toxic megacolon or perforation in the most severe cases.24Tedesco FJ Pseudomembranous colitis: pathogenesis and therapy.Med Clin North Am. 1982; 66: 655-664PubMed Google Scholar, 25Drapkin MS Worthington MG Chang TW Razvi SA Clostridium difficile colitis mimicking acute peritonitis.Arch Surg. 1985; 120: 1321-1322Crossref PubMed Scopus (41) Google Scholar Extraintestinal manifestations such as arthritis are rare.8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 24Tedesco FJ Pseudomembranous colitis: pathogenesis and therapy.Med Clin North Am. 1982; 66: 655-664PubMed Google Scholar, 26Hannonen P Hakola M Mottonen T Oka M Reactive oligo-arthritis associated with Clostridium difficile colitis.Scand J Rheumatol. 1989; 18: 57-60Crossref PubMed Scopus (14) Google Scholar Dehydration, electrolyte depletion, and hypoproteinemia (from a protein-losing colonopathy) may occur with prolonged or severe disease.24Tedesco FJ Pseudomembranous colitis: pathogenesis and therapy.Med Clin North Am. 1982; 66: 655-664PubMed Google Scholar Other complications include hemorrhage, sepsis, and pneumatosis coli. Mortality is low (2%-5%), although it is higher in elderly or debilitated patients (10%-20%) or in those with fulminant colitis or toxic megacolon (30%-80%).27Morris JB Zollinger Jr, RM Stellato TA Role of surgery in antibiotic-induced pseudomembranous enterocolitis.Am J Surg. 1990; 160: 535-539Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 28Synnott K Mealy K Merry C Kyne L Keane C Quill R Timing of surgery for fulminating pseudomembranous colitis.Br J Surg. 1998; 85: 229-231Crossref PubMed Scopus (115) Google Scholar, 29Grundfest-Broniatowski S Quader M Alexander F Walsh RM Lavery I Milsom J Clostridium difficile colitis in the critically ill.Dis Colon Rectum. 1996; 39: 619-623Crossref PubMed Scopus (83) Google Scholar, 30Rubin MS Bodenstein LE Kent KC Severe Clostridium difficile colitis.Dis Colon Rectum. 1995; 38: 350-354Crossref PubMed Scopus (198) Google Scholar In 1 study, the only factor associated with death was delay in the diagnosis of CDAD.27Morris JB Zollinger Jr, RM Stellato TA Role of surgery in antibiotic-induced pseudomembranous enterocolitis.Am J Surg. 1990; 160: 535-539Abstract Full Text PDF PubMed Scopus (110) Google Scholar In some patients (5%-19%), disease will be localized to the proximal colon. These patients may present with an acute abdomen, localized rebound tenderness, no diarrhea, and normal findings on sigmoidoscopy. Considering this diagnosis in such a patient with subsequent confirmation based on stool studies and computed tomography (CT) may help avoid unnecessary surgery.25Drapkin MS Worthington MG Chang TW Razvi SA Clostridium difficile colitis mimicking acute peritonitis.Arch Surg. 1985; 120: 1321-1322Crossref PubMed Scopus (41) Google Scholar After recovery, patients may become asymptomatic carriers of C difficile, but most never have a relapse.31Fekety R Silva J Buggy B Deery HG Treatment of antibiotic-associated colitis with vancomycin.J Antimicrob Chemother. 1984; 14: 97-102Crossref PubMed Google Scholar However, 10% to 20% of patients will experience relapse regardless of the therapeutic agent used to treat CDAD. Such patients usually respond well to re-treatment with metronidazole or vancomycin,8McFarland LV Epidemiology, risk factors and treatments for antibiotic-associated diarrhea.Dig Dis. 1998; 16: 292-307Crossref PubMed Scopus (238) Google Scholar, 31Fekety R Silva J Buggy B Deery HG Treatment of antibiotic-associated colitis with vancomycin.J Antimicrob Chemother. 1984; 14: 97-102Crossref PubMed Google Scholar, 32Surawicz CM McFarland LV Elmer G Chinn J Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii.Am J Gastroenterol. 1989; 84: 1285-1287PubMed Google Scholar but the risk of further recurrences may be as high as 65%.33Fekety R McFarland LV Surawicz CM Greenberg RN Elmer GW Mulligan ME Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.Clin Infect Dis. 1997; 24: 324-333Crossref PubMed Scopus (317) Google Scholar Staphylococcal enterocolitis is an uncommon cause of AAD and is suspected when gram-positive cocci are seen on a stool smear with negative results on C difficile tests.34McDonald M Ward P Harvey K Antibiotic-associated diarrhoea and methicillin-resistant Staphylococcus aureus.Med J Aust. 1982; 1: 462-464PubMed Google Scholar Neutropenic enterocolitis (typhlitis) is suspected when a patient receiving chemotherapy develops diarrhea and abdominal pain in the setting of neutropenia.35Urbach DR Rotstein OD Typhlitis.Can J Surg. 1999; 42: 415-419PubMed Google Scholar Crohn disease and ulcerative colitis can mimic CDAD,36Hermens DJ Miner Jr, PB Exacerbation of ulcerative colitis.Gastroenterology. 1991; 101: 254-262PubMed Google Scholar and C difficile infection can cause a flare in such patients.36Hermens DJ Miner Jr, PB Exacerbation of ulcerative colitis.Gastroenterology. 1991; 101: 254-262PubMed Google Scholar, 37Gryboski JD Clostridium difficile in inflammatory bowel disease relapse.J Pediatr Gastroenterol Nutr. 1991; 13: 39-41Crossref PubMed Scopus (38) Google Scholar Other diseases in the differential diagnosis include chemical colitis (chemotherapy, gold), ischemic colitis, and other infections (Campylobacter, Salmonella, Shigella, Escherichia coli, Listeria, and cytomegalovirus).38Fortson WC Tedesco FJ Drug-induced colitis: a review.Am J Gastroenterol. 1984; 79: 878-883PubMed Google Scholar In general, C difficile is noninvasive. Rare cases of intestinal tissue invasion have been reported in children with malignancy or a compromised immune system.39Qualman SJ Petric M Karmali MA Smith CR Hamilton SR Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.Am J Clin Pathol. 1990; 94: 410-416PubMed Google Scholar The development of CDAD requires an alteration in normal gut flora or mucosal immunity, acquisition and germination of spores, overgrowth of C difficile, and toxin production.40Bartlett JG Chang TW Gurwith M Gorbach SL Onderdonk AB Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia.N Engl J Med. 1978; 298: 531-534Crossref PubMed Scopus (1023) Google Scholar, 41Pothoulakis C Pathogenesis of Clostridium difficile-associated diarrhoea.Eur J Gastroenterol Hepatol. 1996; 8: 1041-1047Crossref PubMed Scopus (91) Google Scholar The most important toxins are toxin A (enterotoxin and cytotoxin) and toxin B (cytotoxin).3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar, 40Bartlett JG Chang TW Gurwith M Gorbach SL Onderdonk AB Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia.N Engl J Med. 1978; 298: 531-534Crossref PubMed Scopus (1023) Google Scholar Toxin A binds to mucosal receptors and causes cytotoxicity by disrupting cytoplasmic microfilaments. Toxin B then enters the damaged mucosa and causes further toxicity, resulting in hemorrhage, inflammation, and necrosis. The toxins interfere with protein synthesis, attract granulocytes, and increase capillary permeability and peristalsis.3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar, 24Tedesco FJ Pseudomembranous colitis: pathogenesis and therapy.Med Clin North Am. 1982; 66: 655-664PubMed Google Scholar, 41Pothoulakis C Pathogenesis of Clostridium difficile-associated diarrhoea.Eur J Gastroenterol Hepatol. 1996; 8: 1041-1047Crossref PubMed Scopus (91) Google Scholar In patients with severe disease, inflammation may involve deep layers, resulting in toxic dilatation or perforation.27Morris JB Zollinger Jr, RM Stellato TA Role of surgery in antibiotic-induced pseudomembranous enterocolitis.Am J Surg. 1990; 160: 535-539Abstract Full Text PDF PubMed Scopus (110) Google Scholar The diagnosis of CDAD is based on a combination of clinical findings, laboratory tests, and sometimes endoscopy. Sudden occurrence of an otherwise unexplained leukocytosis in a hospitalized patient might suggest underlying CDAD and should prompt investigation.42Bulusu M Narayan S Shetler K Triadafilopoulos G Leukocytosis as a harbinger and surrogate marker of Clostridium difficile infection in hospitalized patients with diarrhea.Am J Gastroenterol. 2000; 95: 3137-3141Crossref PubMed Google Scholar Fecal leukocytes can be seen, but their absence does not exclude colitis. Culture for C difficile is demanding and has a low predictive value because of the rate of asymptomatic carriers in antibiotic-treated patients and the prevalence of nonpathogenic isolates.3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar, 15Privitera G Scarpellini P Ortisi G Nicastro G Nicolin R de Lalla F Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery.Antimicrob Agents Chemother. 1991; 35: 208-210Crossref PubMed Scopus (133) Google Scholar Stool cytotoxicity assays are considered positive when cultured cells undergo cytopathic changes after exposure to stool filtrates. The result is confirmed by neutralizing these effects with specific antitoxins. This is considered the gold standard diagnostic method because of its high sensitivity and specificity.3Lyerly DM Krivan HC Wilkins TD Clostridium difficile: its disease and toxins.Clin Microbiol Rev. 1988; 1: 1-18Crossref PubMed Scopus (438) Google Scholar, 43Fekety R American College of Gastroenterology Practice Parameters Committee Guidelines for diagnosis and management of Clostridium difficile-associated diarrhea and colitis.Am J Gastroenterol. 1997; 92: 739-750PubMed Google Scholar Of note, however, 5% to 10% of patients with PMC have negative tests by cytotoxin assay.43Fekety R American College of Gastroenterology Practice Parameters Committee Guidelines for diagnosis and management of Clostridium difficile-associated diarrhea and colitis.Am J Gastroenterol. 1997; 92: 739-750PubMed Google Scholar, 44Gerding DN Brazier JS Optimal methods for identifying Clostridium difficile infections.Clin Infect Dis. 1993; 16: S439-S442Crossref PubMed Scopus (66) Google Scholar Furthermore, cytotoxicity assays are expensive and time consuming. The enzyme-linked immunosorbent assay (ELISA) for detection of toxin A or B is less expensive and faster than the cytotoxicity assay43Fekety R American College of Gastroenterology Practice Parameters Committee Guidelines for diagnosis and management of Clostridium difficile-associated diarrhea and colitis.Am J Gastroenterol. 1997; 92: 739-750PubMed Google Scholar and thus is preferred at many institutions. Sensitivity is lower (75%-85%),43Fekety R American College of Gastroenterology Practice Parameters Committee Guidelines for diagnosis and management of Clostridium difficile-associated diarrhea and colitis.Am J Gastroenterol. 1997; 92: 739-750PubMed Google Scholar but performing the test on 2 to 3 separate stool specimens should increase the sensitivity to the 90% range. A newer ELISA to detect the presence of either toxin has excellent specificity (about 100%) and overall agreement (>98%) compared with the cytotoxicity assay.45Aldeen WE Bingham M Aiderzada A Kucera J Jense S Carroll KC Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools.Diagn Microbiol Infect Dis. 2000; 36: 211-213Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 46Lyerly DM Neville LM Evans DT et al.Multicenter evaluation of Clostridium difficile TOX A/B TEST.J Clin Microbiol. 1998; 36: 184-190PubMed Google Scholar By detecting strains that only produce toxin B, this assay (TOX A/B test) improves sensitivity compared with ELISAs that detect only toxin A.45Aldeen WE Bingham M Aiderzada A Kucera J Jense S Carroll KC Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools.Diagn Microbiol Infect Dis. 2000; 36: 211-213Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 46Lyerly DM Neville LM Evans DT et al.Multicenter evaluation of Clostridium difficile TOX A/B TEST.J Clin Microbiol. 1998; 36: 184-190PubMed Google Scholar The latex agglutination test has poor sensitivity and specificity and does not distinguish toxigenic from nontoxigenic strains.47Lyerly DM Ball DW Toth J Wilkins TD Characterization of cross-reactive proteins detected by Culturette Brand Rapid Latex Test for Clostridium difficile.J Clin Microbiol. 1988; 26: 397-400PubMed Google Scholar Abdominal radiographs may show mucosal edema or ileus and are useful for ruling out megacolon or perforation.7Tedesco FJ Stanley RJ Alpers DH Diagnostic features of clindamycin-associated pseudomembranous colitis.N Engl J Med. 1974; 290: 841-843Crossref PubMed Scopus (75) Google Scholar A barium enema examination has a risk of perforation and precipitating megacolon and therefore is not recommended.7Tedesco FJ Stanley RJ Alpers DH Diagnostic features of clindamycin-associated pseudomembranous colitis.N Engl J Med. 1974; 290: 841-843Crossref PubMed Scopus (75) Google Scholar Abdominal CT may show colonic distention, thickening, pericolonic inflammation, or free air and is most valuable in severe cases and those localized to the proximal colon.25Drapkin MS Worthington MG Chang TW Razvi SA Clostridium difficile colitis mimicking acute peritonitis.Arch Surg. 1985; 120: 1321-1322Crossref PubMed Scopus (41) Google Scholar, 48Yankes JR Baker ME Cooper C Garbutt J CT appearance of focal pseudomembranous colitis.J Comput Assist Tomogr. 1988; 12: 394-396Crossref PubMed Scopus (17) Google Scholar The diagnosis of CDAD is difficult to establish in infants because they commonly carry the organism and toxins. A therapeutic trial with vancomycin may be the only noninvasive method to confirm the clinical importance of toxins in the stool. Although findings on endoscopy may be normal in patients with mild CDAD, most patients have abnormal mucosa, ranging from minimal erythema or edema to ulcerated mucosa, often with nodular exudates, which may coalesce to form yellowish “pseudomembranes”49Gebhard RL Gerding DN Olson MM et al.Clinical and endoscopic findings in patients early in the course of Clostridium difficile-associated pseudomembranous colitis.Am J Med. 1985; 78: 45-48Abstract Full Text PDF PubMed Scopus (68) Google Scholar consisting of mucus and fibrin filled with dead leukocytes and mucosal cells.50Sumner HW Tedesco FJ Rectal biopsy in clindamycin-associated colitis: an analysis of 23 cases.Arch Pathol. 1975; 99: 237-241PubMed Google Scholar Flexible sigmoidoscopy will be diagnostic in most patients, but colonoscopy may be necessary when the disease is localized above the splenic flexure. Endoscopy can suggest CDAD quickly44Gerding DN Brazier JS Optimal methods for identifying Clostridium difficile infections.Clin Infect Dis. 1993; 16: S439-S442Crossref PubMed Scopus (66) Google Scholar, 49Gebhard RL Gerding DN Olson MM et al.Clinical and endoscopic findings in patients early in the course of Clostridium difficile-associated pseudomembranous colitis.Am J Med. 1985; 78: 45-48Abstract Full Text PDF PubMed Scopus (68) Google Scholar and should be safe in a patient with a nondistended abdomen, but it may be dangerous in patients with severe disease with colonic dilatation. In experienced hands, however, gentle flexible sigmoidoscopy with minimal air insufflation may provide the diagnosis and allow initiation of therapy before stool test results are available. In patients with mild CDAD, supportive care alone may be sufficient, including discontinuing or changing the offending antibiotic, rehydration, and enteric isolation of hospitalized patients. Diarrhea will resolve with conservative therapy (ie, no antibiotics) in 15% to 23% of patients.18Bacon AE Fekety R Schaberg DR Faix RG Epidemiology of Clostridium difficile colonization in newborns: results using a bacteriophage and bacteriocin typing system.J Infect Dis. 1988; 158: 349-354Crossref PubMed Scopus (44) Google Scholar, 51Olson MM Shanholtzer CJ Lee Jr, JT Gerding DN Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982–1991.Infect Control Hosp Epidemiol. 1994; 15: 371-381Crossref PubMed Scopus (289) Google Scholar, 52Zimmerman MJ Bak A Sutherland LR Review article: treatment of Clostridium difficile infection.Aliment Pharmacol Ther. 1997; 11: 1003-1012Crossref PubMed Scopus (33) Google Scholar Antidiarrheal agents and narcotics sho
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