Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-05-08T14:16:07.280Z Has data issue: false hasContentIssue false
  • English
  • Français

Clostridium Difficile-Associated Diarrhea and Colitis

Published online by Cambridge University Press:  02 January 2015

Dale N. Gerding ,
Stuart Johnson ,
Lance R. Peterson ,
Maury E. Mulligan  and
Joseph Silva Jr.
Dale N. Gerding
Affiliation:
Veterans Affairs Lakeside Medical Center, Chicago, Illinois Northwestern University Medical School, Chicago, Illinois
Stuart Johnson
Affiliation:
Veterans Affairs Lakeside Medical Center, Chicago, Illinois Northwestern University Medical School, Chicago, Illinois
Lance R. Peterson
Affiliation:
Northwestern University Medical School, Chicago, Illinois
Maury E. Mulligan
Affiliation:
Veterans Affairs Long Beach Medical Center and University of California Irvine Medical School, Long Beach, California
Joseph Silva Jr.
Affiliation:
University of California Davis Medical School, Sacramento, California
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives:

To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile -associated disease (CDAD).

Diagnosis:

A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay.

Epidemiology:

C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly.

Infection Control:

Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction.

Treatment:

Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

Type
SHEA Position Paper
Information
Infection Control & Hospital Epidemiology , Volume 16 , Issue 8 , August 1995 , pp. 459 - 477
Copyright
Copyright © The Society for Healthcare Epidemiology of America 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Lyerly, DM, Krivan, HC, Wilkins, TD. Clostridium difficile its disease and toxins. Clin Microbiol Rev 1988;1:1–18.Google Scholar
2.Gerding, DN. Disease associated with Clostridium difficile infection. Ann Intern Med 1989;110:255–257.Google Scholar
3.McFarland, LV, Stamm, WE. Review of Clostridium difficile-associated diseases. Am J Infect Control 1986;14:99–109.Google Scholar
4.Siegel, DL, Edelstein, PH, Nachamkin, I. Inappropriate testing for diarrheal diseases in the hospital. JAMA 1990;263:979–982.Google Scholar
5.Yannelli, B, Gurevich, I. Schoch, PE, Cunha, BA. Yield of stool cultures, ova and parasite tests, and Clostridium difficile determinations in nosocomial diarrhea. Am J Infect Control 1988;16:246–249.Google Scholar
6.McFarland, LV, Mulligan, M, Kwok, RYY, Stamm, WE. Nosocomial acquisition of Closdridium difficile infection. N Engl J Med 1989;320:204–210.Google Scholar
7.Johnson, S, Clabots, CR, Linn, FV, Olson, MM, Peterson, LR, Gerding, DN. Nosocomial Clostridium difficile colonization and disease. Lancet 1990;336:97–100.Google Scholar
8.Fekety, R, Kim, KH, Brown, D, Batts, DH, Cudmore, M, Silva, J Jr. Epidemiology of antibiotic-associated colitis: isolation of Clostridium difficile from the hospital environment. Am Med 1981;70:906–908.Google Scholar
9.Kelly, CP, Pothoulakis, C, LaMont, JT. Clostridium difficile colitis. N Engl J Med 1994;330:257–262.Google Scholar
10.Gerding, DN, Brazier, JS. Optimal methods for identifying Clostridium difficile infections. Clin Infect Dis 1993;16(suppl 4):S439–S442.Google Scholar
11.Kelly, PJ, Peterson, LRThe role of the clinical microbiology laboratory in the management of Clostridium difficile-associated diarrhea. Infect Dis Clin North Am 1993;7:277–293.Google Scholar
12.Shanholtzer, CJ, Willard, KE, Holter, JJ, et al.Comparison of VIDAS C difficile toxin A immunoassay (CDA) with C difficile culture, cytotoxin, and latex test. J Clin Microbiol 1992;30:1837–1840.Google Scholar
13.Walker, RC, Ruane, PJ, Rosenblatt, JE, et al.Comparison of culture, cytotoxicity assays, and enzyme-linked immunosorbent assay for toxin A and toxin B in the diagnosis of Clostridium difFicile-related enteric disease. Diagn Microbiol Infect Dis 1986;5:61–69.Google Scholar
14.Gerding, 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;146:95–100.Google Scholar
15.Tedesco, FJ, Barton, RW, Alpers, DH. Clindamycin-associated colitis. Ann Intern Med 1974;81:429–433.Google Scholar
16.Bergstein, JM, Kramer, A, Wittman, DH, Aprahamian, C, Quebbeman, EJ. Pseudomembranous colitis: how useful is endoscopy? Surg Endosc 1990;4:217–219.Google Scholar
17.Bowman, RA, Riley, TVLaboratory diagnosis of Clostridium difficile-associated diarrhea. Eur J Clin Microbiol Infect Dis 1988;7:476–484.Google Scholar
18.Peterson, LR, Shanholtzer, CJ. Laboratory methods for the diagnosis of C difficile-related gastrointestinal disease. Lab Manag 1988;26:42–45.Google Scholar
19.Rolfe, RD. Diagnosis of Clostridium difficile-associated intestinal disease. Crit Rev Clin Lab Sci 1986;24:235–261.Google Scholar
20.Bartlett, JG. Antibiotic-associated colitis. Dis Mon 1984;30:1–55.Google Scholar
21.Knoop, FC, Owens, M, Crocker, IC. Clostridium difficile clinical disease and diagnosis. Clin Microbiol Rev 1993;6:257–265.Google Scholar
22.Aronsson, B, Mollby, R, Nord, CE. Diagnosis and epidemiology of Clostridium difficile enterocolitis in Sweden. J Antimicrob Chemother 1984;14(suppl D):85–95.Google Scholar
23.Larson, HE, Parry, JVPrice, AB, et al.Undescribed toxin in pseudomembranous colitis. Br Med 1977;i: 12461248.Google Scholar
24.Bartlett, JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573–581.Google Scholar
25.Borriello, SPWren, BW, Hyde, S, et al.Molecular, immunological, and biological characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile. Infect Immun 1992;60:4192–4199.Google Scholar
26.Lyerly, DM, Barroso, LA, Wilkins, TD, et al.Characterization of a toxin A-negative, toxinB-positive strain of Clostridium difficile. Infect Immun 1992;60:4633–4639.Google Scholar
27.Torres, JEPurification and characterization of toxin B from a strain of Clostridium difficile that does not produce toxin A. J Med Microbiol 1991;35:40–44.Google Scholar
28.Doern, GV, Coughlin, RT, Wu, L. Laboratory diagnosis of Clostridium difficile-associated gastrointestinal disease: comparison of a monoclonal antibody enzyme immunoassay for toxins A and B with a monoclonal antibody enzyme immunoassay for toxin A only and two cytotoxicity assays. J Clin Microbiol 1992;30:2042–2046.Google Scholar
29.Nachamkin, I, Lotz-Nolan, L, Skalina, D. Evaluation of a commercial cytotoxicity assay for detection of Clostridium difficile toxin. J Clin Microbiol 1986;23:954–955.Google Scholar
30.Tichota-Lee, J, Jaqua-Stewart, MJ, Benfield, D, et al.Effect of age on the sensitivity of cell cultures to Clostridium difficile toxin. Diagn Microbiol Infect Dis 1987;8:203–214.Google Scholar
31.Peterson, LR, Olson, MM, Shanholtzer, CJ, et al.Results of a prospective, 18-month clinical evaluation of culture, cytotoxin testing, and culturette brand (CDT) latex testing in the diagnosis of Clostridium difficile-associated diarrhea. Diagn Microbiol Infect Dis 1988;10:85–91.Google Scholar
32.Delmée, M, Mackey, THamitou, AEvaluation of a new commercial Clostridium difficile toxin A enzyme immunoassay using diarrheal stools. Eur J Clin Microbiol Infect Dis 1992;11:246–249.Google Scholar
33.Barbut, F, Kajzer, C, Planas, N, et al.Comparison of three enzyme immunoassays, a cytotoxicity assay and toxigenic culture for the diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 1X%31:963–967.Google Scholar
34.Kurzynski, TA, Kimball, JL, Schultz, DA, et al.Evaluation of C diff-Cube test for detection of Clostridium difficile-associated diarrhea. Diagn Microbiol Infect Dis 1992;15:493–498.Google Scholar
35.Woods, GL, Iwen, PC. Comparison of a dot immunobinding assay, latex agglutination, and cytotoxin assay for laboratory diagnosis of Clostridium difficile-associated dianhea. J Clin Microbiol 1990;28:855–857.Google Scholar
36.Borriello, SP, Vale, T, Brazier, JS, Hyde, S, Chippeck, E. Evaluation of a commercial enzyme immunoassay kit for the detection of Clostridium difficile toxin A Eur J Clin Microbiol Infect Dis 1992;11:360–363.Google Scholar
37.DeGirolami, PC, Hanff, PA, Eichelberger, K, et al.Multicenter evaluation of a new enzyme immunoassay for detection of Clostridium difficile enterotoxin. A. J Clin Microbiol 1992;30:1085–1088.Google Scholar
38.DiPersio, JR, Varga, FJ, Conwell, DL, Kraft, IA, Kozak, KJ, Willis, DH. Development of a rapid enzyme immunoassay for Clostridium difficile toxin A and its use in the diagnosis of C difficile-associated disease. J Clin Microbiol 1991;29:2724–2730.Google Scholar
39.Altaie, SS, Meyer, P, Dryja, D. Comparison of two commercially available enzyme immunoassays for detection of Clostridium difficile in stool specimens. J Clin Microbiol 1994;32:51–53.Google Scholar
40.Whittier, S, Shapiro, DS, Kelly, WEet al.Evaluation of four commercially available enzyme immunoassays for laboratory diagnosis of Clostridium difficile-associated disease. J Clin Microbiol 1993;31:2861–2865.Google Scholar
41.Merz, CS, Kramer, C, Formen, M, et al.Comparison of four commercially available rapid enzyme immunoassays with cytotoxin assay for detection of Clostridium difficile toxins from stool specimens. J Clin Microbiol 1994;32:1142–1147.Google Scholar
42.Arrow, SA, Croese, L, Bowman, RA, Riley, TVEvaluation of three commercial enzyme immunoassay kits for detecting faecal Clostridium difficile toxins. J Clin Pathol 1994;47:954–956.Google Scholar
43.George, WL, Sutter, VL, Citron, D, et al.Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol 1979;9:214–219.Google Scholar
44.Levett, PN. Effect of antibiotic concentration in a selective medium on the isolation of Clostridium difficile from faecal specimens. J Clin Pathol 1985;38:233–234.Google Scholar
45.Shanholtzer, CJ, Peterson, LRLaboratory quality assurance testing of microbiologic media from commercial sources, Am J Clin Pathol 1987;88:210–215.Google Scholar
46.Aspinall, ST, Hutchinson, DN. New selective medium for isolating Clostridium difficile from faeces. J Clin Pathol 1992;45:812–814.Google Scholar
47.Bartley, SL, Dowell, VR Jr. Comparison of media for the isolation of Clostridium difficile from fecal specimens. Lab Med 1991;22:335–338.Google Scholar
48.Iwen, PC, Booth, SJ, Woods, GL. Comparison of media for screening of dianheic stools for the recovery of Clostridium difficile. J Clin Microbiol 1989;27:2105–2106.Google Scholar
49.Mundy, LS, Shanholtzer, CJ, Willard, KE, Gerding, DN, Peterson, LRLaboratory detection of Clostridium difficile: a comparison of media and incubation conditions, Am J Clin Pathol 1994;103:52–56.Google Scholar
50.Marler, LM, Siders, JA, Wolters, LC, Pettigrew, Y, Skirt, BL, Allen, SD. Comparison of five cultural procedures for isolation of Clostridium difficile from stools. J Clin Microbiol 1992;30:514–516.Google Scholar
51.Peterson, LR, Holter, JJ, Shanholtzer, CJ. et al.Detection of Clostridium difficile toxins A (enterotoxin) and B (cytotoxin) in clinical specimens. Evaluation of a latex agglutination test. Am J Clin Pathol 1986;86:208211.Google Scholar
52.Berg, JD, Mills, RG, Coleman, DJ. Improved gasliquid chromatography method for the identification of Clostridium difficile. J Clin Pathol 1985;38:108–110.Google Scholar
53.Aspinall, STDealler, SENew rapid identification test for Clostridium difficile. J Clin Pathol 1992;45:956–958.Google Scholar
54.Bate, G. Comparison of Minitek Anaerobe II®, API An-Ident®, and Rapid ANA® systems for identification of Clostridium difficile. Am J Clin Pathol 1986;85:716–718.Google Scholar
55.Gresser, ME, Shanholtzer, CJ, Gerding, DN, et al.Evaluation of the 24-h API Anaerobe System® for identification of Clostridium difficile. J Clin Microbiol 1984;19:915–916.Google Scholar
56.Clabots, CR, Johnson, S, olson, MM, et al.Clostridium difficile-associated diarrhea (CDAD) diagnosis in patients with positive stool culture (CULT) and negative stool cytotoxin (CTX) assays (Abstract #1567). In: Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology. Washington, DC; 1993.Google Scholar
57.Lyerly, DM, Wilkins, TD. Commercial latex test for Clostridium difficile toxin A does not detect toxin A J Clin Microbiol 1986;23:622–623.Google Scholar
58.Lyerly, DM, Barroso, LA, Wilkins, TD. Identification of the latex test-reactive protein of Clostridium diffficile as glutamate dehydrogenase. J Clin Microbiol 1991;29:2639–2642.Google Scholar
59.Wren, BW, Clayton, CL, Castledine, NB, et al.Identification of toxigenic Clostridium difficile strains by using a toxin A gene-specific probe. J Clin Microbiol 1990;28:1808–1812.Google Scholar
60.Phelps, CJ, Lyerly, DL, Johnson, JL, et al.Construction and expression of the complete Clostridium difficile toxin A gene in Escherichia coll. Infect Immun 1991;59:150–153.Google Scholar
61.Kato, N, Ou, C-Y, Kato, H, et al.Identification of toxigenic Clostridium difficile by the polymerase chain reaction. J Clin Microbiol 1991;29:33–37.Google Scholar
62.McMillin, DE, Muldrow, LL. Laggette, SJ, et al.Simultaneous detection of toxin A and toxin B genetic determinants of Clostridium difficile using the multiplex polymerase chain reaction. Can J Microbiol 1992;38:81–83.Google Scholar
63.Wren, B, Clayton, C, Tabaqchali, S. Rapid identification of toxigenic Clostridium difficile strains by polymerase chain reaction. Lancet 1990;335:423.Google Scholar
64.Gumerlock, PH, Tang, YJ, Weiss, JB, Silva, J Jr. Specific detection of toxigenic strains of Clostridium difficile in stool specimens. J Clin Microbiol 1993;31:507–511.Google Scholar
65.Kuhl, SJ, Tang, YJ, Navarro, L, Gummerlock, PH, Silva, J Jr. Diagnosis and monitoring of Clostridium difficile infections with the polymerase chain reaction. Clin Infect Dis 1993;16(suppl 4):S234–S238.Google Scholar
66.Levine, HG, Kennedy, M, LaMont, JTCounterimmunoelectrophoresis vs cytotoxicity for the detection of Clostridium difficile toxin. J Infect Dis 1982;145:398.Google Scholar
67.Madan, E, Slifkin, M. Stool caproic acid for screening of Clostridium difficile. Am J Clin Pathol 1988;89:525–527.Google Scholar
68.Shanholtzer, CJ, Peterson, LR, Olson, MM, et al.Prospective study of Gram-stained stool smears in diagnosis of Clostridium difficile colitis. J Clin Microbiol 1983;17:906–908.Google Scholar
69.West, SEH, Wilkins, TD. Problems associated with counterimmunoelectrophoresis assays for detecting Clostridium difficile toxin. J Clin Microbiol 1982;15:347–349.Google Scholar
70.Hall, IC, O'Toole, E. Intestinal flora in new-born infants. Am J Dis Child 1935;49:390–402.Google Scholar
71.Hafiz, S, Oakley, CL. Clostridium difficile: isolation and characteristics. J Med Microbiol 1976;9:129–136.Google Scholar
72.Finney, JM. Gast-enterostomy for cicatrizing ulcer of the pylorus. Johns Hopkins Hosp Bull 1893;11:53–55.Google Scholar
73.Bartlett, JG, Chang, TW, Gurwith, M, Gorbach, SL, Onderdonk, AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing Clostridia. N Engl J Med 1978;298:531–543.Google Scholar
74.Larson, HE, Honour, PPrice, AB, Borriello, SPClostridium difficile and the etiology of pseudomembranous colitis. Lancet 1978;i:1063–1066.Google Scholar
75.Viscidi, R, Wiley, S, Bartlett, JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5–9.Google Scholar
76.Aronsson, B, Mollby, , Nord, C-E. Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiologic data from Sweden, 198(11982. J Infect Dis 1985;151:476–481.Google Scholar
77.Nakamura, S, Mikawa, M, Takabatake, M, et al.Isolation of Clostridium difficile from the feces and antibody in sera of young and elderly adults. Microbiol Immunol 1981;25:345351.Google Scholar
78.Larson, HE, Barclay, FE, Honour, P, Hill, ID. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982;146:727–733.Google Scholar
79.Burdon, DW. Clostridium difficile: the epidemiology and prevention of hospital-acquired infection. Infection 1982;10:203–204.Google Scholar
80.Toshniwal, R, Silva, J Jr, Fekety, R, Kim, K-H. Studies on the epidemiology of colitis due to Clostridium difficile in hamsters. J Infect Dis 1981;143:51–54.Google Scholar
81.Larson, HE, Price, AB, Borriello, SPEpidemiology of experimental enterocolitis due to Clostridium difficile. J Infect Dis 1980;42:408–413.Google Scholar
82.Greenfield, C, Aguilar Ramirez, JR, Pounder, RE, et al.Clostridium difficile and inflammatory bowel disease. Gut 1983;24:713–717.Google Scholar
83.Bender, BS, Bennett, R, Laughon, BE, et al.Is Clostridium difficile endemic in chronic care facilities? Lancet 1986;ii:11–13.Google Scholar
84.Yablon, SA, Krotenberg, R, Fruhmann, K. Clostridium difficile-related disease: evaluation and prevalence among inpatients with diarrhea in two freestanding rehabilitation hospitals. Arch Phys Med Rehabil 1993;74:913.Google Scholar
85.Hirschhorn, LR, Trnka, Y, Onderdonk, A, Lee, M-LT, Piatt, REpidemiology of community-acquired Clostridium difficileu-associated diarrhea. J Infect Dis 1994;169:127–133.Google Scholar
86.Akhtar, SQ. Isolation of Clostridium difficile from diarrhea patients in Bangladesh. J Trop Med Hyg 1987;90:189192.Google Scholar
87.Ayyagari, A, Sharma, P, Venkateswarlu, , Mehta, S, Agarwal, KC. Prevalence of Clostridium difficile in pseudomembranous and antibiotic-associated colitis in north India. J Diarrhoeal Dis Res 1986;4:157–160.Google Scholar
88.Pear, S, Williamson, T, Bettin, K, Gerding, DN, Galgiani, JN. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med 1994;120:272–277.Google Scholar
89.Thibault, A, Miller, MA, Gaese, C. Risk factors for the development of Clostridium difficile-associated diarrhea during a hospital outbreak. Infect Control Hosp Epidemiol 1991;12:34M48.Google Scholar
90.Yee, J, Dixon, CM, McLean, APH, Meakins, JL. Clostridium difficile disease in a department of surgery: the significance of prophylactic antibiotics. Arch Surg 1991;126:241–246.Google Scholar
91.Anand, A, Glatt, AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993;17:109–113.Google Scholar
92.Pierce, PF Jr, Wilson, R, Silva, J Jret al.Antibiotic-associated pseudomembranous colitis: an epidemiologic investigation of a cluster of cases. J Infect Dis 1982;145:269–274.Google Scholar
93.McFarland, LV, Surawicz, CM, Stamm, WE. Risk factors for Clostridium difficile carriage and Clostridium difficile-associated diarrhea in a cohort of hospitalized patients J Infect Dis 1990;162:678–684.Google Scholar
94.Milligan, DW, Kelly, JK. Pseudomembraneous colitis in a leukaemia unit: a report of five total cases. J Clin Pathol 1979;32:1237–1243.Google Scholar
95.Barbut, F, Depitre, C, Delmee, M, Corthier, G, Petit, JC. Comparison of enterotoxin production, cytotoxin production, serogrouping, and antimicrobial susceptibilities of Clostridium difficile strains isolated from AIDS and human immunodeficiency vims-negative patients. J Clin Microbiol 1993;31:740–742.Google Scholar
96.Roberts, MC, McFarland, LV, Mullany, P, Mulligan, ME. Characterization of the genetic basis of antibiotic resistance in Clostridium difficile. J Antimicrob Chemother 1994;33:419–429.Google Scholar
97.McFarland, LV, Elmer, GW, Stamm, WE, Mulligan, ME. Correlation of immunoblot type, enterotoxin production, and cytotoxin production with clinical manifestations of Clostridium difficile infection in a cohort of hospitalized patients. Infect Immun 1991;59:2456–2462.Google Scholar
98.Peach, SL, Borriello, SPGaya, FE, et al.Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis. J Clin Pathol 1986;39:1013–1018.Google Scholar
99.Warny, M, Vaerman, J-P, Avesani, V, Delmée, M. Human antibody response to Clostridium dificile toxin A in relation to clinical course of infection. Infect Immun 1994;62:384–389.Google Scholar
100.Mulligan, ME, Miller, SD, McFarland, LV, Fung, HC, Kwok, RYY. Elevated levels of serum immunoglobulins in asymptomatic carriers of Clostridium difficile. Clin Infect Dis 1993;16;239–244.Google Scholar
101.Johnson, S, Gerding, DN, Janoff, EN. Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile. J Infect Dis 1992;166:1287–1294.Google Scholar
102.Kelly, CP, Pothoulakis, C, Orellana, J, LaMont, JT. Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A-receptor binding. Gastroenterology 1992;102:35–40.Google Scholar
103.Samore, MH, Bettin, KM, DeGirolami, PC, et al.Wide diversity of Clostridium difficile types at a tertiary referral hospital. J Infect Dis 1994;170:615–621.Google Scholar
104.Johnson, S, Adelnann, A, Clabots, CR, Peterson, LR, Gerding, DN. Recurrences of Clostridium difficile diarrhea not caused by the original infecting organism. J Infect Dis 1989;159:340–343.Google Scholar
105.O'Neill, GL, Beaman, MH, Riley, TVRelapse versus reinfection with Clostridium difficile. Epidemiol Infect 1991;107:627–635.Google Scholar
106.Clabots, CR, Johnson, S, Olson, MM, Peterson, LR, Gerding, DN. Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis 1992;166:561–567.Google Scholar
107.Heard, SR, Wren, B, Barnett, MJ, Thomas, JM, Tabaqchali, S. Clostridium difficile infection in patients with haematological malignant disease. Epidemiol Infect 1988;100:63–72.Google Scholar
108.Clabots, CR, Peterson, LH, Gerding, DN. Characterization of a nosocomial Clostridium difficile outbreak by using plasmid profile typing and clindamycin susceptibility testing. J Infect Dis 1988;158:731–736.Google Scholar
109.Johnson, S, Gerding, DN, Olson, MM, et al.Prospective, controlled study of vinyl glove use to interrupt Clostridium difficile nosocomial transmission. Am J Med 1990;88:137–140.Google Scholar
110.Malamou-Ladas, H, Farrell, SO, Nash, JO, Tabaqchali, S. Isolation of Clostridium difficile from patients and the environment of hospital wards. J Clin Pathol 1983;6:8&92.Google Scholar
111.Mulligan, ME, Rolfe, RD, Finegold, SM, George, WLContamination of a hospital environment by Clostridium difficile. Curr Microbiol 1979;3:173–175.Google Scholar
112.Savage, AM, Alford, RH. Nosocomial spread of Clostridium difficile. Infect Control 1983;4:31–33.Google Scholar
113.Brooks, SE, Veal, RO, Kramer, M, Dore, L, Schupf, N, Adachi, M. Reduction in the incidence of Clostridium difficile-associated diarrhea in an acute care hospital and a skilled nursing facility following replacement of electronic thermometers with single-use disposables. Infect Control Hosp Epidemiol 1992;13:98103.Google Scholar
114.Brooks, S, Real, R, Kramer, M, Adachi, M. Clostridium difficile-associated diarrhea. Infect Control Hosp Epidemiol 1990,11:574.Google Scholar
115.Mogg, GAG, Keighly, MRB, Burdon, DW, et al.Antibiotic associated colitis-a review of 66 cases. Br J Surg 1979;66:738–742.Google Scholar
116.Gurian, L, Ward, TT, Katon, RM. Possible foodborne transmission in a case of pseudomembranous colitis due to Clostridium difficile. Gastroenterology 1982;83:465–469.Google Scholar
117.Oishi, JS, Mulligan, ME, Finegold, SM. Failure to detect Clostridium diffficile in foods. J Infect Dis 1983;148:360.Google Scholar
118.Kim, K-H, Fekety, R, Batts, DH, et al.Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic associated colitis. J Infect Dis 1981;143:42–50.Google Scholar
119.Borriello, P, Honour, P, Turner, T, Barclay, F. Household pets as a potential reservoir for Clostridium difficile infection. J. Clin Pathol 1983;36:84–87.Google Scholar
120.Riley, TVAdams, JE, O'Neill, GL, Bowman, RA. Gastrointestinal carriage of Clostridium difficile in cats and dogs attending veterinary clinics. Epidemiol Infect 1991;107:659–665.Google Scholar
121.Hafiz, S, Morton, RS, McEntegart, MG, Waitkins, SA. Clostridium difficile in the urogenital tract of males and females. Lancet 1975;i:420–421.Google Scholar
122.Al-Jumaili, U, Shibley, M, Lishmann, AH, Record, CO. Incidence and origin of Clostridium difficile in neonates J Clin Microbiol 1984;19:77–78.Google Scholar
123.Clabots, CR, Johnson, S, Bettin, KM, et al.Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol 1993;31:1870–1876.Google Scholar
124.Wolfhagen, MJHM, Fluit, AC, Torensma, R, et al.Comparison of typing methods for Clostridium difficile isolates. J Clin Microbiol 1993;31:2208–2211.Google Scholar
125.Tabaqchali, S. Epidemiologic markers of Clostridium difficile. Rev Infect Dis 1990;12(suppl 2):S192–S198.Google Scholar
126.Tabaqchali, S, Holland, D, O'Farrell, S, Silman, R, Typing scheme for Clostridium difficile. Its application in clinical and epidemiological studies. Lancet 1984;1:935–938.Google Scholar
127.Poxton, IR, Aronsson, B, Molby, R, Nord, CE. Collee, JG. Immunochemical fingerprinting of Clostridium difficile strains isolated from an outbreak of antibiotic-associated colitis and diarrhea. J Med Microbiol 1984;17:317–324.Google Scholar
128.Mulligan, ME, Peterson, LR, Kwok, RYY, Clabots, CR, Gerding, DN. Immunoblots and plasmid fingerprints compared with serotyping and polyacrylamide gel electrophoresis for typing Clostridium difficile. J Clin Microbiol 1988;26:41–46.Google Scholar
129.Kato, H, Cavallaro, JJ, Kato, N, et al.Typing of Clostridium difficile by western immunoblotting with 10 different antisera. J Clin Microbiol 1993;31:413–415.Google Scholar
130.Delmee, M, Avesani, V, Delferriere, , Burtonboy, G. Characterization of flagella of Clostridium difficile and their role in serogrouping reactions. J Clin Microbiol 1990;28:2210–2214.Google Scholar
131.Sell, TL, Schaberg, DR, Fekety, FRBacteriophage and bacteriocin typing scheme for Clostridium difficile. J Clin Microbiol 1983;17:1147–1152.Google Scholar
132.Dei, R. Observations on phage-typing of Clostridium difficile: preliminay evaluation of a phage panel. Eur J Epidemiol 1989;5:351–354.Google Scholar
133.Bowman, RA. O'Neill, GL, Riley, TVNon-radioactive restriction fragment length polymorphism (RFLP) typing of Clostridium difficile. FEMS Microbiol Lett 1991;63:269–272.Google Scholar
134.Kristjansson, M, Samore, MH, Gerding, DN, et al.Molecular differentiation of Clostridium difficile: a comparison of restriction endonuclease analysis, ribotyping. and pulsed field gel electrophoresis. J Clin Microbiol 1994;32:1963–1969.Google Scholar
135.McMillin, DE, Muldrow, LL. Typing of toxic strains of Clostridium difficile using DNA fingerprints generated with arbitrary polymerase chain reaction primers. FEMS Microbiol Lett 1992;71:5–9.Google Scholar
136.Wren, BW, Heard, SR, al-Saleh, Al, Tabaqchali, S. Characterization of Clostridium difficile strains by polymerase chain reaction with toxin A-and B- specific polymers. J Med Microbiol 1993;38:109–113.Google Scholar
137.Silva, J JrTang, YJ, Gumerlock, PH. Genotyping of Clostridium difficile isolates. J Infect Dis 1994;169:661–664.Google Scholar
138.Bettin, K, Clabots, C, Mathie, P, Willard, K, Gerding, DN. Effectiveness of soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands. Infect Control Hosp Epidemiol 1994;15:697–702.Google Scholar
139.Nolan, NPM, Kelly, CP, Humphreys, JFH, et al.An epidemic of pseudomembranous colitis: importance of person-to-person spread. Gut 1987;28:1467–1473.Google Scholar
140.Brown, E, Talbot, GM, Axelrod, P, Provencher, M, Hoegg, C. Risk factors for Clostridium difficile toxin-associated diarrhea. Infect Control Hosp Epidemiol 1990;11:283–290.Google Scholar
141.Wilcox, MH, Spencer, RC. Clostridium difficile infection: responses, relapses and re-infections. J Hosp Infect 1992;22:85–92.Google Scholar
142.Struelens, MJ, Maas, A, Nonhoff, C, et al.Control of nosocomial transmission of Clostridium difficile based on sporadic case surveillance. Am J Med 1991;91(suppl 3B): 1385–1445.Google Scholar
143.Olson, MM, Shanholtzer, MT, Lee, JT JrGerding, 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;15:371–381.Google Scholar
144.Hughes, CE, Gebhard, RL, Peterson, LR, Gerding, DN. Efficacy of routine fiberoptic endoscope cleaning and disinfection for killing Clostridium difficile. Gastrointest Endosc 1986;32:7–9.Google Scholar
145.Rutala, WA, Gergen, MEWeber, DJ. Inactivation of Clostridium difficile spores by disinfectants. Infect Control Hosp Epidemiol 1993;14:3&39.Google Scholar
146.Kaatz, GW, Gitlin, SD, Schaberg, DR, et al.Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol 1988;127:1289–1294.Google Scholar
147.Delmee, M, Vandercam, B, Avesani, V, Michaux, JL. Epidemiology and prevention of Clostridium difficile infections in a leukemia unit. Eur J Clin Microbiol 1987;6:623–627.Google Scholar
148.Samore, MH, DeGirolami, PC, Tlucko, A, Lichtenberg, DA, Melvin, ZA, Karchmer, AW. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–187.Google Scholar
149.Kerr, RB, McLaughlin, DI, Sonnenberg, LW. Control of Clostridium difficile colitis outbreak by treating asymptomatic carriers with metronidazole. Am J Infect Control 1990;18:332–335.Google Scholar
150.Hoverstad, TCarlstedt-Duke, B, Lingaas, E, et al.Influence of ampicilliln, clindamycin, and mnetronidazole on faecal excretion of short-chain fatty acids in healthy subjects. Scand J Gastroenterol 1986;21:621–628.Google Scholar
151.Arabi, Y, Dimock, F, Burdon, DW, Alexander-Willliams, J, Keighley, MRB. Influence of neomycin and metronidazole on colonic microflora of volunteers. J Antimicrob Chemother 1979;5:531–537.Google Scholar
152.Johnson, S, Homann, SR, Bettin, KM, et al.Treatment of asymptomatic Clostridium dificile carriers (fecal excretors) with vancomycin or metronidazole. Ann Intern Med 1992;117:297–302.Google Scholar
153.Bartlett, JG. Antimicrobial agents implicated in Clostridium difficile toxin associated diarrhea or colitis. Johns Hopkins Med J 1981;149:6–9.Google Scholar
154.Surawicz, CM, Elmer, GW, Speelman, P, McFarland, LV, Chinn, J, Van Belle, G. Prevention of antibiotic-associated dianhea by Saccharomyces boulardii: a prospective study. Gastroenterology 1989;96:981–988.Google Scholar
155.Lyerly, DM, Bostwick, EFBinion, SB, Wilkins, TD. Passive immunization of hamsters against disease caused by Clostridium didficile by use of bovine immunoglobulin G concentrate. Infect Immun 1991;59:2215–2218.Google Scholar
156.Davidson, GP, Daniels, E, Nunan, H, et al.Passive immunization of children with bovine colostrum containing antibodies to human rotavirus. Lancet 1989;2:709–712.Google Scholar
157.Tacket, CO, Losonsky, G, Link, H, et al.Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N Engl J Med 1988;318:1240–1243.Google Scholar
158.Reid, G, Bruce, AW, McGroarty, JA, Cheng, K-J, Costerton, JW. Is there a role for lactobacilli in prevention of urogenital and intestinal infections? Clin Microbiol Rev 1990;3:335–344.Google Scholar
159.Siitonen, S, Vapaatalo, H. Salminen, S, et al.Effect of Lactobacillus GG yogurt in prevention of antibiotic associated diarrhea. Ann Intern Med 1990;22:57059.Google Scholar
160.Gorbach, S. Lactic acid bacteria and health. Ann Intern Med 1990;22:37–41.Google Scholar
161.Kotz, CM, Peterson, LR, Moody, JA, Savaiano, DA, Levitt, MD. Effect of yogurt on clindamycin-induced Clostridium difficile colitis in hamsters. Dig Dis Sci 1992;37:129–132.Google Scholar
162.Teasley, DG. Gerding, DN, Olson, MM, et al.Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficile-associated dianhea and colitis. Lancet 1983;ii:1043–1046.Google Scholar
163.Bartlett, JG. The 10 most common questions about Clostridium difficile-associated dianhea/colitis. Infect Dis Clin Pract 1992;1:254–259.Google Scholar
164.Kleinfeld, DI, Sharpe, RJ, Donta, ST. Parenteral therapy for antibiotic-associated pseudomembranous colitis. J Infect Dis 1988;157:389.Google Scholar
165.Bolton, RPCulshaw, MA. Fecal metronidazole concentrations during oral and intravenous therapy for antibiotic-associated colitis due to Clostridium difficile. Gut 1986;27:1169–1172.Google Scholar
166.Peterson, LR. Gerding, DN. Antimicrobial agents in Clostridium difficile-associated intestinal disease. In: Rambaud, J-C, Ducluzeau, R, eds. Clostridium difficile-Associated Intestinal Diseases. Paris, France: Springer-Verlag; 1990:115–127.Google Scholar
167.George, WL. Rolfe, RD, Finegold, SM. Treatment and prevention of antimicrobial agent-induced colitis and diarrhea. Gastroenterology 1980;79:366–372.Google Scholar
168.Cone, JB, Wetzel, W. Toxic megacolon secondary to pseudomembranous colitis. Dis Colon Rectum 1982;25:478–482.Google Scholar
169.Finegold, SM, George, WL. Therapy directed against Clostridium difficile and its toxins: complications of therapy. In: Rolfe, RD, George, WL, eds. Clostridium difficile: Its Role in Intestinal Disease. New York, New York: Academic Press: 1988:341–357.Google Scholar
170.Silva, J Jr. Batts, DH, Fekety, R, Plouffe, IF, Rifkin, GD, Baird, I. Treatment of Clostridium dificile colitis and diarrhea with vancomycin. Am J Med 1981;71:815–822.Google Scholar
171.Ings, RM, McFadzean, JA. Ormerod, WE. The fate of metronidazole and its implications in chemotherapy. Xenobiotica 1975;5:223–235.Google Scholar
172.Fekety, R, Shah, ABDiagnosis and treatment of Clostridium difficile colitis. JAMA 1993;269:71–75.Google Scholar
173.Fekety, R, Silva, J, Kauffman, C, Buggy, B, Deery, G. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989;86:15–19.Google Scholar
174.Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycin resistant-e. Infect Control Hosp Epidemiol 1995;16:105113.Google Scholar
175.deLalla, F, Nicolin, R, Rinaldi, E, et al.Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium dififcile-associated dianhea. Antimicrob Agents Chemother 1992;36:2192–2196.Google Scholar
176.Dudley, MN, McLaughlin, JC. Carrington, G, Frick, J, Nightingale, CH. Quintiliani, R. Oral bacitracin versus vancomycin therapy for Clostridium difficile-induced diarrhea: a randomized, double-blind trial. Arch Intern Med 1986;146:1101–1104.Google Scholar
177.Young, GP, Ward, PB, Bayley, N, et al.Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Gastroenterology 1985;89:1038–1045.Google Scholar
178.Mogg, GAG, Arabi, Y, Youngs, D, et al.Therapeutic trials of antibiotic associated colitis. Scand J Infect Dis 1980;(suppl 22):41–45.Google Scholar
179.Levett, PN. Time-dependent killing of Clostridium difficile by metronidazole and vancomycin. J Antimicrob Chemother 1991;27:55–62.Google Scholar
180.Surawicz, CM, McFarland, LV, Elmer, G, Chin, J. Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii. Am J Gastroenterol 1989;84:1285–1287.Google Scholar
181.Buggy, BEFekety, R, Silva, J Jr. Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomy-and rifampin. J Clin Gastroenterol 1987;9:155159.Google Scholar
182.Gorbach, SL, Chang, TW, Goldin, B. Successful treatment of relapsing Clostridium dificile colitis with lactobacillus GG. Lancet 1987;ii:1519.Google Scholar
183.Moncino, MD, Falletta, JM. Multiple relapses of Clostridium difficile-associated diarrhea in a cancer patient: successful control with long-term therapy. Am J Pediatr Hematol Oncol 1992;14:361–364.Google Scholar
184.Pruksananonda, P, Powell, KR. Multiple relapses of Clostridium difficile-associated diarrhea responding to an extended course of cholestyramine. Pediatr Infect Dis J 1989;8:175178.Google Scholar
185.Tvede, M, Rask-Madsen, J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhea in six patients. Lancet 1989;i:1156–1160.Google Scholar
186.Seal, D, Borriello, SF: Barclay, F, Welch, A, Piper, M, Bonnycastle, M. Treatment of relapsing Clostridium difficile diarrhea by administration of a non-toxigenic strain. Eur J Clin Microbiol 1987;6:51–53.Google Scholar
187.Tedesco, FJ, Gordon, D. Fortson, WC. Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis. Am J Gastroenterol 1985;80:867–868.Google Scholar
188.McFarland, LV, Surawicz, CM, Greenberg, RN, et al.Randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. J Amer Med Worn Assoc 1994;271:1913–1918.Google Scholar
189.Leung, DYM, Kelly, CP, Boguniewicz, M, Pothoulakis, C, LaMont, JTFlores, A. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991;118:633–637.Google Scholar
190.Morris, JB, Zollinger, RM, Stellato, TA. Role of surgery in antibiotic-induced pseudomembranous colitis. Am J Surg 1990;160:535–539.Google Scholar
191.Silva, J Jr. Update on pseudomembranous colitis. West J Med l989;151:644–648.Google Scholar
192.Nath, SK. Thornley, JH, Kelly, M, et al.A sustained outbreak of Clostridium difficile in a general hospital: persistence of a toxigenic clone in four units. Infect Control Hosp Epidemiol 1994;15:382–389.Google Scholar
193.Silva, J Jr. Clostridium difficile nosocomial infections-still lethal and persistent. Infect Control Hosp Epidemiol 1994;15:368–370.Google Scholar
194.Gross, PA, Barret, TL, Dellinger, EPet al.Consensus development of quality standards. Infect Control Hosp Epidemiol 1994;15:18@181.Google Scholar
195.Bartlett, JG. Treatment of Clostridium difficile colitis. Gastroenterology 1985;89:1192–1195.Google Scholar