Hostname: page-component-5db58dd55d-d6ndz Total loading time: 0 Render date: 2026-05-30T10:51:13.056Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA)

Published online by Cambridge University Press:  02 January 2015

Stuart H. Cohen ,
Dale N. Gerding ,
Stuart Johnson ,
Ciaran P. Kelly ,
Vivian G. Loo ,
L. Clifford McDonald ,
Jacques Pepin  and
Mark H. Wilcox
Stuart H. Cohen
Affiliation:
Department of Internal Medicine, Division of Infectious and Immunologic Diseases, University of California Davis Medical Center, Sacramento, California
Dale N. Gerding
Affiliation:
Research Service, Edward Hines Jr. Veterans Affairs Hospital, and Infectious Disease Division, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois
Stuart Johnson
Affiliation:
Research Service, Edward Hines Jr. Veterans Affairs Hospital, and Infectious Disease Division, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois
Ciaran P. Kelly
Affiliation:
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Vivian G. Loo
Affiliation:
Department of Microbiology, McGill University Health Center, Montreal, Quebec, Canada
L. Clifford McDonald
Affiliation:
Division of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
Jacques Pepin
Affiliation:
Department of Microbiology and Infectious Diseases, University of Sherbrooke, Quebec, Canada
Mark H. Wilcox
Affiliation:
Department of Microbiology, Leeds Teaching Hospitals National Health Service Trust and Institute of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom
Get access Rights & Permissions [Opens in a new window]

Abstract

Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcare-associated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.

Information

Type
SHEA-IDSA Guideline
Information
Infection Control & Hospital Epidemiology , Volume 31 , Issue 5 , May 2010 , pp. 431 - 455
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2010 

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.)

Article purchase

Temporarily unavailable

References

1. McFarland, LV, Mulligan, ME, Kwok, RY, et al. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204–210.Google Scholar
2. Shanholtzer, CJ, Willard, KE, Holter, JJ, et al. Comparison of the VIDAS Clostridium difficile toxin A immunoassay with C. difficile culture and cytotoxin and latex tests. J Clin Microbiol 1992;30:1837–1840.Google Scholar
3. Shim, JK, Johnson, S, Samore, MH, et al. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998;351:633–636.Google Scholar
4. 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
5. Kyne, L, Warny, M, Qamar, A, et al. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000;342:390–397.Google Scholar
6. Louie, TJ, Peppe, J, Watt, CK, et al. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea. Clin Infect Dis 2006;43:411–420.Google Scholar
7. Musher, DM, Logan, N, Hamill, RJ, et al. Nitazoxanide for the treatment of Clostridium diffidle colitis. Clin Infect Dis 2006;43:421–427.Google Scholar
8. Kuijper, EJ, Coignard, B, Tuli, P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006;12(Suppl 6):2–18.Google Scholar
9. 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
10. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388–416.Google Scholar
11. Kyne, L, Merry, C, O'Connell, B, et al. Factors associated with prolonged symptoms and severe disease due to Clostridium difficile . Age Ageing 1999;28:107–113.Google Scholar
12. Bartlett, JG. Antibiotic-associated colitis. Dis Mon 1984;30:1–54.Google Scholar
13. Bartlett, JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 2002;346:334–349.Google Scholar
14. Kelly, CP, Pothoulakis, C, LaMont, JT. Clostridium diffidle colitis. N Engl J Med 1994;330:257–262.Google Scholar
15. Hall, IC, O'Toole, E. Intestinal flora in new-born infants. Am J Dis Child 1935;49:390–402.Google Scholar
16. Viscidi, R, Willey, S, Bartlett, JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5–9.Google Scholar
17. Aronsson, B, Mollby, R, Nord, CE. Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiological data from Sweden, 1980-1982. J Infect Dis 1985;151:476–481.Google Scholar
18. Nakamura, S, Mikawa, M, Nakashio, S, et al. Isolation of Clostridium diffidle from the feces and the antibody in sera of young and elderly adults. Microbiol Immunol 1981;25:345–351.Google Scholar
19. Burdon, DW. Clostridium difficile, the epidemiology and prevention of hospital-acquired infection. Infection 1982;10:203–204.Google Scholar
20. Larson, HE, Barclay, FE, Honour, P, et al. Epidemiology of Clostridium diffidle in infants. J Infect Dis 1982;146:727–733.Google Scholar
21. Larson, HE, Price, AB, Bordello, SP. Epidemiology of experimental en-terocecitis due to Clostridium difficile . J Infect Dis 1980;142:408–413.Google Scholar
22. Toshniwal, R, Silva, J Jr, Fekety, R, et al. Studies on the epidemiology of colitis due to Clostridium difficile in hamsters. J Infect Dis 1981;143:51–54.Google Scholar
23. Johnson, S, Clabots, CR, Linn, FV, et al. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97–100.Google Scholar
24. McDonald, LC, Killgore, GE, Thompson, A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile . NEngl J Med 2005;353:2433–2441.Google Scholar
25. Loo, VG, Poirier, L, Miller, MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium diffidle-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:2442–2449.Google Scholar
26. Voth, DE, Ballard, JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005;18:247–263.Google Scholar
27. Samore, MH, DeGirolami, PC, Tlucko, A, et al. Clostridium diffidle colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–187.Google Scholar
28. Olson, MM, Shanholtzer, CJ, Lee, JT Jr, et al. Ten years of prospective Clostridium diffidle-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994;15:371–381.Google Scholar
29. Triadafilopoulos, G, Hailstone, AE. Acute abdomen as the first presentation of pseudomembranous colitis. Gastroenterology 1991;101:685–691.Google Scholar
30. Wolf, LE, Gorbach, SL, Granowitz, EV. Extraintestinal Clostridium difficile: 10 years' experience at a tertiary-care hospital. Mayo Clin Proc 1998;73:943–947.Google Scholar
31. Pron, B, Merckx, J, Touzet, P, et al. Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile . Eur J Clin Microbiol Infect Dis 1995;14:599–601.Google Scholar
32. Studemeister, AE, Beilke, MA, Kirmani, N. Splenic abscess due to Clostridium difficile and Pseudomonas paucimobilis . Am J Gastroenterol 1987;82:389–390.Google Scholar
33. Feldman, RJ, Kallich, M, Weinstein, MP. Bacteremia due to Clostridium difficile: case report and review of extraintestinal C. difficile infections. Clin Infect Dis 1995;20:1560–1562.Google Scholar
34. Freiler, JF, Durning, SJ, Ender, PT. Clostridium diffidle small bowel enteritis occurring after total colectomy. Clin Infect Dis 2001;33:1429–1431.Google Scholar
35. Wanahita, A, Goldsmith, EA, Marino, BJ, et al. Clostridium diffidle infection in patients with unexplained leukocytosis. Am J Med 2003;115:543–546.Google Scholar
36. Wanahita, A, Goldsmith, EA, Musher, DM. Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by Clostridium difficile . Clin Infect Dis 2002;34:1585–1592.Google Scholar
37. Gerding, DN, Johnson, S, Peterson, LR, et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459–477.Google Scholar
38. Field, MJ, Lohr, KN. Institute of Medicine Committee to Advise the Public Health Service on Clinical Practice Guidelines, Clinical Practice Guidelines: Directions for a New Program. Washington, DC: Institute of Medicine; 1990.Google Scholar
39. The periodic health examination. Canadian Task Force on the Periodic Health Examination. Can Med Assoc J 1979;121:1193–1254.Google Scholar
40. Miller, MA, Hyland, M, Ofher-Agostini, M, et al. Morbidity, mortality, and healthcare burden of nosocomial Clostridium difficile-associated diarrhea in Canadian hospitals. Infect Control Hosp Epidemiol 2002;23:137–140.Google Scholar
41. Miller, MA, Gravel, D, Mulvey, M, et al. Surveillance for nosocomial Clostridium difficile associated diarrhea (N-CDAD) within acute-care hospitals in Canada: results of the 2005 nosocomial infections surveillance program (CNISP) study shows escalating mortality. In: Proceedings of the 16th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America; March 18-21, 2006; Chicago, IL.Google Scholar
42. Walker, KJ, Gilliland, SS, Vance-Bryan, K, et al. Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors. J Am Geriatr Soc 1993;41:940–946.Google Scholar
43. Simor, AE, Bradley, SF, Strausbaugh, LJ, et al. Clostridium difficile in long-term-care facilities for the elderly. Infect Control Hosp Epidemiol 2002;23:696–703.Google Scholar
44. Kyne, L, Hamel, MB, Polavaram, R, et al. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile . Clin Infect Dis 2002;34:346–353.Google Scholar
45. O'Brien, JA, Lahue, BJ, Caro, JJ, et al. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol 2007;28:1219–1227.Google Scholar
46. McDonald, LC, Owings, M, Jernigan, DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis 2006;12:409–415.Google Scholar
47. Pepin, J, Alary, ME, Valiquette, L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005;40:1591–1597.Google Scholar
48. Muto, CA, Pokrywka, M, Shutt, K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26:273–280.Google Scholar
49. Centers for Disease Control and Prevention. Data and statistics about Clostridium difficile infections Web page, http://www.cdc.gov/ncidod/dhqp/id_Cdiff_data.html. Accessed February 22, 2010.Google Scholar
50. Eggertson, L. Quebec strain of C. difficile in 7 provinces. Can Med Assoc 2006;174:607–608.Google Scholar
51. Warny, M, Pepin, J, Fang, A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079–1084.Google Scholar
52. Health Protection Agency. Outbreak of Clostridium difficile infection in a hospital in southeast England. CDR Weekly 2005;15(24).Google Scholar
53. Kuijper, EJ, Debast, SB, Van Kregten, E, et al. Clostridium difficile ribo-type 027, toxinotype III in The Netherlands [in Dutch]. Ned Tijdschr Geneeskd 2005;149:2087–2089.Google Scholar
54. Kuijper, EJ, Barbut, F, Brazier, JS, et al. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill 2008;13(31):pii:18942.Google Scholar
55. Kato, H, Ito, Y, van den Berg, RJ, et al. First isolation of Clostridium difficile 027 in Japan. Euro Surveill 2007;12:E0701113.Google Scholar
56. Severe Clostridium difficile-associated disease in populations previously at low risk-four states, 2005. MMWR Morb Mortal Wkly Rep 2005;54:1201–1205.Google Scholar
57. James, AH, Katz, VL, Dotters, DJ, et al. Clostridium difficile infection in obstetric and gynecologic patients. South Med J 1997;90:889–892.Google Scholar
58. Kyne, L, Merry, C, O'Connell, B, et al. Community-acquired Clostridium diffidle infection. J Infect 1998;36:287–288.Google Scholar
59. Johal, SS, Hammond, J, Solomon, K, et al. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004;53:673–677.Google Scholar
60. Terhes, G, Urban, E, Sold, J, et al. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A, and toxin B gene-positive isolates in Hungary. J Clin Microbiol 2004;42:4316–4318.Google Scholar
61. Dial, S, Delaney, JA, Barkun, AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium diffidle-associated disease. JAMA 2005;294:2989–2995.Google Scholar
62. Hirschhorn, LR, Trnka, Y, Onderdonk, A, et al. Epidemiology of community-acquired Clostridium difficile-associated diarrhea. J Infect Dis 1994;169:127–133.Google Scholar
63. Levy, DG, Stergachis, A, McFarland, LV, et al. Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting. Clin Ther 2000;22:91–102.Google Scholar
64. Frost, F, Hurley, JS, Petersen, HV, et al. Estimated incidence of Clostridium difficile infection. Emerg Infect Dis 1999;5:303–304.Google Scholar
65. Rivera, EV, Woods, S. Prevalence of asymptomatic Clostridium difficile colonization in a nursing home population: a cross-sectional study. J Gend Specif Med 2003;6:27–30.Google Scholar
66. Fekety, R, Kim, KH, Brown, D, et al. Epidemiology of antibiotic-associated colitis: isolation of Clostridium difficile from the hospital environment. Am J Med 1981;70:906–908.Google Scholar
67. Riggs, MM, Sethi, AK, Zabarsky, TF, et al. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis 2007;45:992–998.Google Scholar
68. McFarland, LV, Surawicz, CM, Greenberg, RN, et al. Possible role of cross-transmission between neonates and mothers with recurrent Clostridium difficile infections. Am J Infect Control 1999;27:301–303.Google Scholar
69. Kyne, L, Warny, M, Qamar, A, et al. Association between antibody response to toxin A and protection against recurrent Clostridium diffidle diarrhoea. Lancet 2001;357:189–193.Google Scholar
70. Sambol, SP, Tang, JK, Merrigan, MM, et al. Infection of hamsters with epidemiologically important strains of Clostridium difficile . J Infect Dis 2001;183:1760–1766.Google Scholar
71. Anand, A, Bashey, B, Mir, T, et al. Epidemiology, clinical manifestations, and outcome of Clostridium difficile-associated diarrhea. Am J Gastroenterol 1994;89:519–523.Google Scholar
72. Palmore, TN, Sohn, S, Malak, SF, et al. Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital. Infect Control Hosp Epidemiol 2005;26:680–684.Google Scholar
73. Chang, H, Parada, J, Evans, C, et al. Onset of symptoms and time to diagnosis of Clostridium difficile diarrhea among outpatients discharged from an acute care hospital [abstract]. In: Proceedings of The 16th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America; March 18-21, 2006; Chicago, IL: 108–109.Google Scholar
74. Mayfield, J, McMullen, K, Dubberke, E. Comparison of Clostridium diffidle-associated disease rates using a traditional vs. expanded definition. In: Proceedings of The 16th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America; March 18-21, 2006; Chicago, IL: 115.Google Scholar
75. Samore, MH, Venkataraman, L, DeGirolami, PC, et al. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996;100:32–40.Google Scholar
76. Mayfield, JL, Leet, T, Miller, J, et al. Environmental control to reduce transmission of Clostridium difficile . Clin Infect Dis 2000;31:995–1000.Google Scholar
77. Fawley, WN, Wilcox, MH. Molecular epidemiology of endemic Clostridium diffidle infection. Epidemiol Infect 2001;126:343–350.Google Scholar
78. Wilcox, MH, Fawley, WN, Wigglesworth, N, et al. Comparison of the effect of detergent versus hypochlorite cleaning on environmental contamination and incidence of Clostridium difficile infection. J Hosp Infect 2003;54:109–114.Google Scholar
79. Brooks, SE, Veal, RO, Kramer, M, et al. Reduction in the incidence of Clostridium diffidle-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;13:98–103.Google Scholar
80. Pepin, J, Valiquette, L, Alary, ME, et al. Clostridium diffidle-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 2004;171:466–472.Google Scholar
81. Johnson, S, Samore, MH, Farrow, KA, et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med 1999;341:1645–1651.Google Scholar
82. Privitera, G, Scarpellini, P, Ortisi, G, et al. Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother 1991;35:208–210.Google Scholar
83. Yee, J, Dixon, CM, McLean, AP, et al. Clostridium difficile disease in a department of surgery: the significance of prophylactic antibiotics. Arch Surg 1991;126:241–246.Google Scholar
84. Anand, A, Glatt, AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993;17:109–113.Google Scholar
85. Morales Chamorro, R, Serrano Blanch, R, Mendez Vidal, MJ, et al. Pseudomembranous colitis associated with chemotherapy with 5-fluoro-uracil. Clin Transi Oncol 2005;7:258–261.Google Scholar
86. Bilgrami, S, Feingold, JM, Dorsky, D, et al. Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1999;23:1039–1042.Google Scholar
87. Gorschluter, M, Glasmacher, A, Hahn, C, et al. Clostridium difficile infection in patients with neutropenia. Clin Infect Dis 2001;33:786–791.Google Scholar
88. Sanchez, TH, Brooks, JT, Sullivan, PS, et al. Bacterial diarrhea in persons with HIV infection, United States, 1992-2002. Clin Infect Dis 2005;41:1621–1627.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;12:345–348.Google Scholar
90. Bliss, DZ, Johnson, S, Savik, K, et al. Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feeding. Ann Intern Med 1998;129:1012–1019.Google Scholar
91. Cunningham, R, Dale, B, Undy, B, et al. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect 2003;54:243–245.Google Scholar
92. Dial, S, Alrasadi, K, Manoukian, C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 2004;171:33–38.Google Scholar
93. Al-Jumaili, IJ, Shibley, M, Lishman, AH, et al. Incidence and origin of Clostridium difficile in neonates. J Clin Microbiol 1984;19:77–78.Google Scholar
94. Shah, S, Lewis, A, Leopold, D, et al. Gastric acid suppression does not promote clostridial diarrhoea in the elderly. QJM 2000;93:175–181.Google Scholar
95. McDonald, LC, Coignard, B, Dubberke, E, et al. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007;28:140–145.Google Scholar
96. Cohen, SH, Tang, YJ, Silva, J Jr. Molecular typing methods for the epidemiological identification of Clostridium difficile strains. Expert Rev Moi Diagn 2001;1:61–70.Google Scholar
97. Tang, YJ, Houston, ST, Gumerlock, PH, et al. Comparison of arbitrarily primed PCR with restriction endonuclease and immunoblot analyses for typing Clostridium difficile isolates. J Clin Microbiol 1995;33:3169–3173.Google Scholar
98. Gal, M, Northey, G, Brazier, JS. A modified pulsed-field gel electrophoresis (PFGE) protocol for subtyping previously non—PFGE typeable isolates of Clostridium diffidle polymerase chain reaction ribotype 001. J Hosp Infect 2005;61:231–236.Google Scholar
99. Rupnik, M, Avesani, V, Jane, M, et al. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol 1998;36:2240–2247.Google Scholar
100. Wullt, M, Burman, LG, Laureil, MH, et al. Comparison of AP-PCR typing and PCR-ribotyping for estimation of nosocomial transmission of Clostridium difficile . J Hosp Infect 2003;55:124–130.Google Scholar
101. Northey, G, Gal, M, Rahmati, A, et al. Subtyping of Clostridium difficile PCR ribotype 001 by REP-PCR and PFGE. J Med Microbiol 2005;54:543–547.Google Scholar
102. Stubbs, SL, Brazier, JS, O'Neill, GL, et al. PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium diffidle and construction of a library consisting of 116 different PCR ribotypes. J Clin Microbiol 1999;37:461–463.Google Scholar
103. Lemee, L, Bourgeois, I, Ruffin, E, et al. Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile . Microbiology 2005;151:3171–3180.Google Scholar
104. Marsh, JW, O'Leary, MM, Shutt, KA, et al. Multilocus variable-number tandem-repeat analysis for investigation of Clostridium difficile transmission in hospitals. J Clin Microbiol 2006;44:2558–2566.Google Scholar
105. van den Berg, RJ, Schaap, I, Templeton, KE, et al. Typing and subtyping of Clostridium difficile isolates by using multiple-locus variable-number tandem-repeat analysis. J Clin Microbiol 2007;45:1024–1028.Google Scholar
106. Killgore, G, Thompson, A, Johnson, S, et al. Comparison of seven techniques for typing international epidemic strains of Clostridium difficile. restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. J Clin Microbiol 2008;46:431–437.Google Scholar
107. Lyras, D, O'Connor, JR, Howarth, PM, et al. Toxin B is essential for virulence of Clostridium diffidle . Nature 2009;458:1176–1179.Google Scholar
108. Alfa, MJ, Swan, B, VanDekerkhove, B, et al. The diagnosis of Clostridium difficile-associated diarrhea: comparison of Triage C. diffidle panel, EIA for Tox A/B and cytotoxin assays. Diagn Microbiol Infect Dis 2002;43:257–263.Google Scholar
109. Fedorko, DP, Engler, HD, O'Shaughnessy, EM, et al. Evaluation of two rapid assays for detection of Clostridium difficile toxin A in stool specimens. J Clin Microbiol 1999;37:3044–3047.Google Scholar
110. Ticehurst, JR, Aird, DZ, Dam, LM, et al. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol 2006;44:1145–1149.Google Scholar
111. Planche, T, Aghaizu, A, Holliman, R, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 2008;8:777–784.Google Scholar
112. Wilcox, MH, Eastwood, KA. Clostridium difficile toxin detection assays. Evaluation report CEP08054. NHS Purchasing and Supplies Agency, Centre for Evidence Based Purchasing, 2009. http://www.pasa.nhs.uk/pasa/Doc.aspx?Path=%5bMN%5d%5bSP%5d/NHSprocurement/CEP/CEP08054.pdf. Accessed August 14, 2009.Google Scholar
113. Bouza, E, Munoz, P, Alonso, R. Clinical manifestations, treatment and control of infections caused by Clostridium difficile . Clin Microbiol Infect 2005;11(Suppl 4):57–64.Google Scholar
114. Kuijper, EJ, van den Berg, RJ, Debast, S, et al. Clostridium difficile ribotype 027, toxinotype III, the Netherlands. Emerg Infect Dis 2006;12:827–830.Google Scholar
115. Reller, ME, Lema, CA, Perl, TM, et al. Yield of stool culture with isolate toxin testing versus a two-step algorithm including stool toxin testing for detection of toxigenic Clostridium difficile . J Clin Microbiol 2007;45:3601–3605.Google Scholar
116. Gerding, DN. Diagnosis of Clostridium difficile-associated disease: patient selection and test perfection. Am J Med 1996;100:485–486.Google Scholar
117. Katz, DA, Lynch, ME, Littenberg, B. Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea. Am J Med 1996;100:487–495.Google Scholar
118. Aichinger, E, Schleck, CD, Harmsen, WS, et al. Nonutility of repeat laboratory testing for detection of Clostridium difficile by use of PCR or enzyme immunoassay. J Clin Microbiol 2008;46:3795–3797.Google Scholar
119. Larson, HE, Parry, JV, Price, AB, et al. Undescribed toxin in pseudomembranous colitis. Br Med J 1977;1:1246–1248.Google Scholar
120. Barbut, F, Lalande, V, Burghoffer, B, et al. Prevalence and genetic characterization of toxin A variant strains of Clostridium difficile among adults and children with diarrhea in France. J Clin Miaobiol 2002;40:2079–2083.Google Scholar
121. 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
122. 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
123. Johnson, S, Kent, SA, O'Leary, KJ, et al. Fatal pseudomembranous colitis associated with a variant Clostridium difficile strain not detected by toxin A immunoassay. Ann Intern Med 2001;135:434–438.Google Scholar
124. 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
125. Wilcox, MH, Fawley, WN, Parnell, P. Value of lysozyme agar incorporation and alkaline thioglycollate exposure for the environmental recovery of Clostridium diffidle . J Hosp Infect 2000;44:65–69.Google Scholar
126. Snell, H, Ramos, M, Longo, S, et al. Performance of the Tech Lab C. DIFF CHEK-60 enzyme immunoassay (EIA) in combination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 2004;42:4863–4865.Google Scholar
127. Zheng, L, Keller, SF, Lyerly, DM, et al. Multicenter evaluation of a new screening test that detects Clostridium difficile in fecal specimens. J Clin Microbiol 2004;42:3837–3840.Google Scholar
128. Barbut, F, Lalande, V, Daprey, G, et al. Usefulness of simultaneous detection of toxin A and glutamate dehydrogenase for the diagnosis of Clostridium difficile-associated diseases. Eur J Clin Microbiol Infect Dis 2000;19:481–484.Google Scholar
129. Massey, V, Gregson, DB, Chagla, AH, et al. Clinical usefulness of components of the Triage immunoassay, enzyme immunoassay for toxins A and B, and cytotoxin B tissue culture assay for the diagnosis of Clostridium difficile diarrhea. Am J Clin Pathol 2003;119:45–49.Google Scholar
130. Sloan, LM, Duresko, BJ, Gustafson, DR, et al. Comparison of real-time PCR for detection of the tcdC gene with four toxin immunoassays and culture in diagnosis of Clostridium diffidle infection, J Clin Microbiol 2008;46:1996–2001.Google Scholar
131. Vonberg, RP, Kuijper, EJ, Wilcox, MH, et al. Infection control measures to limit the spread of Clostridium difficile . Clin Microbiol Infect 2008;14(Suppl 5):2–20.Google Scholar
132. Clabots, CR, Johnson, S, Olson, MM, et al. 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
133. Zafar, AB, Gaydos, LA, Furlong, WB, et al. Effectiveness of infection control program in controlling nosocomial Clostridium difficile . Am J Infect Control 1998;26:588–593.Google Scholar
134. Apisarnthanarak, A, Zack, JE, Mayfield, JL, et al. Effectiveness of environmental and infection control programs to reduce transmission of Clostridium difficile . Clin Infect Dis 2004;39:601–602.Google Scholar
135. Stone, SP, Berk, V, Quick, A, et al. The effect of an enhanced infection-control policy on the incidence of Clostridium difficile infection and methicillin-resistant Staphyloccocus aureus colonization in acute elderly medical patients. Age Ageing 1998;27:561–568.Google Scholar
136. Cartmill, TD, Panigrahi, H, Worsley, MA, et al. Management and control of a large outbreak of diarrhoea due to Clostridium difficile , J Hosp Infect 1994;27:1–15.Google Scholar
137. Boyce, JM, Pittet, D. Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep 2002;51:1–45.Google Scholar
138. Pittet, D, Mourouga, P, Perneger, TV. Compliance with handwashing in a teaching hospital. Infection Control Program. Ann Intern Med 1999;130:126–130.Google Scholar
139. Boyce, JM. Using alcohol for hand antisepsis: dispelling old myths. Infect Control Hosp Epidemiol 2000;21:438–441.Google Scholar
140. Teare, L, Cookson, B, Stone, S. Hand hygiene. BMJ 2001;323:411–412.Google Scholar
141. Wullt, M, Odenholt, I, Walder, M. Activity of three disinfectants and acidified nitrite against Clostridium diffidle spores. Infect Control Hosp Epidemiol 2003;24:765–768.Google Scholar
142. Clabots, CR, Gerding, SJ, Olson, MM, et al. Detection of asymptomatic Clostridium difficile carriage by an alcohol shock procedure. J Clin Microbiol 1989;27:2386–2387.Google Scholar
143. Gordin, FM, Schultz, ME, Huber, RA, et al. Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub. Infect Control Hosp Epidemiol 2005;26:650–653.Google Scholar
144. Oughton, M, Loo, V, Fenn, S, Lynch, A, Libman, M. Alcohol rub and antiseptic wipes are inferior to soap and water for removal of Clostridium difficile by handwashing. In: Proceedings of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007; Chicago, IL. Washington, DC: ASM Press; 2007.Google Scholar
145. Bettin, K, Clabots, C, Mathie, P, et al. Effectiveness of liquid 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
146. Struelens, MJ, Maas, A, Nonhoff, C, et al. Control of nosocomial transmission of Clostridium difficile based on sporadic case surveillance. Am J Med 1991;91:138S–144S.Google Scholar
147. Cartmill, TD, Shrimpton, SB, Panigrahi, H, et al. Nosocomial diarrhoea due to a single strain of Clostridium difficile, a prolonged outbreak in elderly patients. Age Ageing 1992;21:245–249.Google Scholar
148. Lai, KK, Melvin, ZS, Menard, MJ, et al. Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control, infect Control Hosp Epidemiol 1997;18:628–632.Google Scholar
149. Garner, JS. Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1996;17:53–80.Google Scholar
150. 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
151. Perry, C, Marshall, R, Jones, E. Bacterial contamination of uniforms. J Hosp Infect 2001;48:238–241.Google Scholar
152. Berild, D, Smaabrekke, L, Halvorsen, DS, et al. Clostridium difficile infections related to antibiotic use and infection control facilities in two university hospitals. J Hosp infect 2003;54:202–206.Google Scholar
153. Dettenkofer, M, Seegers, S, Antes, G, et al. Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review. Infect Control Hosp Epidemiol 2004;25:21–25.Google Scholar
154. The American Institute of Architects Academy of Architecture for Health and the Facilities Guidelines Institute. Guidelines for design and construction of health care facilities. Washington, DC: American Institute of Architects Press, 2006.Google Scholar
155. Strimling, MO, Sacho, H, Berkowitz, I. Clostridium difficile infection in health-care workers. Lancet 1989;2:866–867.Google Scholar
156. Arfons, L, Ray, AJ, Donskey, CJ. Clostridium difficile infection among health care workers receiving antibiotic therapy. Clin Infect Dis 2005;40:1384–1385.Google Scholar
157. Cohen, RS, DiMarino, AJ Jr, Allen, ML. Fecal Clostridium difficile carriage among medical housestaff. N J Med 1994;91:327–330.Google Scholar
158. Brown, E, Talbot, GH, Axelrod, P, et al. Risk factors for Clostridium difficile toxin-associated diarrhea, infect Control Hosp Epidemiol 1990 11:283–290.Google Scholar
159. Delmee, M, Vandercam, B, Avesani, V, et al. Epidemiology and prevention of Clostridium difficile infections in a leukemia unit. Eur J Clin Microbiol 1987;6:623–627.Google Scholar
160. Bender, BS, Bennett, R, Laughon, BE, et al. Is Clostridium difficile endemic in chronic-care facilities? Lancet 1986;2:11–13.Google Scholar
161. Johnson, S, Homann, SR, Bettin, KM, et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole: a randomized, placebo-controlled trial. Ann Intern Med 1992;117:297–302.Google Scholar
162. Hota, B. Contamination, disinfection, and cross-colonization: are hospital surfaces reservoirs for nosocomial infection? Clin Infect Dis 2004;39:1182–1189.Google Scholar
163. O'Neill, G, Adams, JE, Bowman, RA, et al. A molecular characterization of Clostridium diffidle isolates from humans, animals and their environments. Epidemiol Infect 1993;111:257–264.Google Scholar
164. Kim, KH, 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
165. Fawley, WN, Underwood, S, Freeman, J, et al. Efficacy of hospital cleaning agents and germicides against epidemic Clostridium difficile strains. Infect Control Hosp Epidemiol 2007;28:920–925.Google Scholar
166. Manian, FA, Meyer, L, Jenne, J. Clostridium difficile contamination of blood pressure cuffs: a call for a closer look at gloving practices in the era of universal precautions. Infect Control Hosp Epidemiol 1996;17:180–182.Google Scholar
167. Brooks, S, Khan, A, Stoica, D, et al. Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers. Infect Control Hosp Epidemiol 1998;19:333–336.Google Scholar
168. Jernigan, JA, Siegman-Igra, Y, Guerrant, RC, et al. A randomized crossover study of disposable thermometers for prevention of Clostridium difficile and other nosocomial infections. Infect Control Hosp Epidemiol 1998;19:494-49.Google Scholar
169. 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
170. Boyce, JM, Havill, NL, Otter, JA, et al. Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting. Infect Control Hosp Epidemiol 2008;29:723–729.Google Scholar
171. Rutala, WA, Gergen, MF, Weber, DJ. Inactivation of Clostridium difficile spores by disinfectants. Infect Control Hosp Epidemiol 1993;14:36–39.Google Scholar
172. Block, C. The effect of Perasafe and sodium dichloroisocyanurate (NaDCC) against spores of Clostridium diffidle and Badllus atrophaeus on stainless steel and polyvinyl chloride surfaces. J Hosp Infect 2004;57:144–148.Google Scholar
173. Perez, J, Springthorpe, VS, Sattar, SA. Activity of selected oxidizing microbicides against the spores of Clostridium diffidle-. relevance to environmental control. Am J Infect Control 2005;33:320–325.Google Scholar
174. Chang, HT, Krezolek, D, Johnson, S, et al. Onset of symptoms and time to diagnosis of Clostridium difficile-associated disease following discharge from an acute care hospital. Infect Control Hosp Epidemiol 2007;28:926–931.Google Scholar
175. McFarland, LV, 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;162:678–684.Google Scholar
176. Wistrom, J, Norrby, SR, Myhre, EB, et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001;47:43–50.Google Scholar
177. Bignardi, GE. Risk factors for Clostridium diffidle infection. J Hosp Infect 1998;40:1–15.Google Scholar
178. Davey, P, Brown, E, Fenelon, L, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2005;19:CD003543.Google Scholar
179. Pear, SM, Williamson, TH, Bettin, KM, et al. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med 1994;120:272–277.Google Scholar
180. Climo, MW, Israel, DS, Wong, ES, et al. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium diffidle-associzted diarrhea and cost. Ann Intern Med 1998;128:989–995.Google Scholar
181. Carling, P, Fung, T, Killion, A, et al. Favorable impact of a multidisci-plinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003;24:699–706.Google Scholar
182. McNulty, C, Logan, M, Donald, IP, et al. Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy. J Antimicrob Chemother 1997;40:707–711.Google Scholar
183. Khan, R, Cheesbrough, J. Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital. J Hosp Infed 2003;54:104–108.Google Scholar
184. Wilcox, MH, Freeman, J, Fawley, W, et al. Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea. J Antimicrob Chemother 2004;54:168–172.Google Scholar
185. Alston, WK, Ahem, JW. Increase in the rate of nosocomial Clostridium diffidle-associated diarrhoea during shortages of piperacillin-tazobactam and piperacillin. J Antimicrob Chemother 2004;53:549–550.Google Scholar
186. Valiquette, L, Cossette, B, Garant, MP, et al. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associzted disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007;45(Suppl 2):S112–S121.Google Scholar
187. Gaynes, R, Rimland, D, Killum, E, et al. Outbreak of Clostridium diffidle infection in a long-term care facility: association with gatifloxacin use. Clin Infect Dis 2004;38:640–645.Google Scholar
188. Biller, P, Shank, B, Lind, L, et al. Moxifloxacin therapy as a risk factor for Clostridium difficile-associzted disease during an outbreak: attempts to control a new epidemic strain. Infect Control Hosp Epidemiol 2007;28:198–201.Google Scholar
189. Hickson, M, D'Souza, AL, Muthu, N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;335:80.Google Scholar
190. Teasley, DG, Gerding, DN, Olson, MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhoea and colitis. Lancet 1983;2:1043–1046.Google Scholar
191. Wenisch, C, Parschalk, B, Hasenhundl, M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium diffidle-associated diarrhea. Clin Infect Dis 1996;22:813–818.Google Scholar
192. Wullt, M, Odenholt, I. A double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium diffidle-associated diarrhoea. J Antimicrob Chemother 2004;54:211–216.Google Scholar
193. Bricker, E, Garg, R, Nelson, R, Loza, A, Novak, T, Hansen, J. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2005(1):CD004610.Google Scholar
194. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep 1995;44(RR-12):1–13.Google Scholar
195. Fekety, R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 1997;92:739–750.Google Scholar
196. Bolton, RP, Culshaw, MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile . Gut 1986;27:1169–1172.Google Scholar
197. Keighley, MR, Burdon, DW, Arabi, Y, et al. Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea. BMJ 1978;2:1667–1669.Google Scholar
198. Baird, DR. Comparison of two oral formulations of vancomycin for treatment of diarrhoea associated with Clostridium difficile . J Antimicrob Chemother 1989;23:167–169.Google Scholar
199. Olsson-Liljequist, B, Nord, CE. In vitro susceptibility of anaerobic bacteria to nitroimidazoles. Scand J Infect Dis Suppl 1981;26:42–45.Google Scholar
200. Wong, SS, Woo, PC, Luk, WK, et al. Susceptibility testing of Clostridium difficile against metronidazole and vancomycin by disk diffusion and Etest. Diagn Microbiol Infect Dis 1999;34:1–6.Google Scholar
201. Freeman, J, Stott, J, Baines, SD, et al. Surveillance for resistance to metronidazole and vancomycin in genotypically distinct and UK epidemic Clostridium difficile isolates in a large teaching hospital. J Antimicrob Chemother 2005;56:988–989.Google Scholar
202. Drummond, LJ, McCoubrey, J, Smith, DG, et al. Changes in sensitivity patterns to selected antibiotics in Clostridium difficile in geriatric inpatients over an 18-month period. J Med Microbiol 2003;52:259–263.Google Scholar
203. Aspevall, O, Lundberg, A, Burman, LG, et al. Antimicrobial susceptibility pattern of Clostridium difficile and its relation to PCR ribotypes in a Swedish university hospital. Antimicrob Agents Chemother 2006;50:1890–1892.Google Scholar
204. Pelaez, T, Alcala, L, Alonso, R, et al. In vitro activity of ramoplanin against Clostridium difficile, including strains with reduced susceptibility to vancomycin or with resistance to metronidazole. Antimicrob Agents Chemother 2005;49:1157–1159.Google Scholar
205. Baines, SD, O'Connor, R, Freeman, J, et al. Emergence of reduced susceptibility to metronidazole in Clostridium difficile . J Antimicrob Chemother 2008;62:1046–1052.Google Scholar
206. Musher, DM, Aslam, S, Logan, N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 2005;40:1586–1590.Google Scholar
207. Bishara, J, Bloch, Y, Garty, M, et al. Antimicrobial resistance of Clostridium difficile isolates in a tertiary medical center, Israel. Diagn Microbiol Infect Dis 2006;54:141–144.Google Scholar
208. Lamontagne, F, Labbe, AC, Haeck, O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007;245:267–272.Google Scholar
209. Belmares, J, Gerding, DN, Parada, JP, et al. Outcome of metronidazole therapy for Clostridium difficile disease and correlation with a scoring system. J Infect 2007;55:495–501.Google Scholar
210. Pepin, J, Valiquette, L, Gagnon, S, et al. Outcomes of Clostridium difficile-associated disease treated with metronidazole or vancomycin before and after the emergence of NAP 1/027. Am J Gastroenterol 2007;102:2781–2788.Google Scholar
211. Zar, FA, Bakkanagari, SR, Moorthi, KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45:302–307.Google Scholar
212. Louie, T, Gerson, M, Grimard, D, et al. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhea (CDAD). In: Proceedings of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007; Chicago, IL. Washington, DC: ASM Press; 2007. Abstract K-425aGoogle Scholar
213. Apisarnthanarak, A, Razavi, B, Mundy, LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis 2002;35:690–696.Google Scholar
214. McPherson, S, Rees, CJ, Ellis, R, et al. Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea. Dis Colon Rectum 2006;49:640–645.Google Scholar
215. Longo, WE, Mazuski, JE, Virgo, KS, et al. Outcome after colectomy for Clostridium difficile colitis. Dis Colon Rectum 2004;47:1620–1626.Google Scholar
216. Bartlett, JG. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1984;6(Suppl 1):S235–S241.Google Scholar
217. Bartlett, JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573–581.Google Scholar
218. Barbut, F, Richard, A, Hamadi, K, et al. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol 2000;38:2386–2388.Google Scholar
219. Johnson, S, Adelmann, A, Clabots, CR, et al. Recurrences of Clostridium difficile diarrhea not caused by the original infecting organism. J Infect Dis 1989;159:340–33.Google Scholar
220. Pepin, J, Saheb, N, Coulombe, MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium diffidle-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254–1260.Google Scholar
221. Nair, S, Yadav, D, Corpuz, M, et al. Clostridium difficile colitis: factors influencing treatment failure and relapse-a prospective evaluation. Am J Gastroenterol 1998;93:1873–1876.Google Scholar
222. Pepin, J, Routhier, S, Gagnon, S, et al. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis 2006;42:758–764.Google Scholar
223. Kapoor, K, Chandra, M, Nag, D, et al. Evaluation of metronidazole toxicity: a prospective study. Int J Clin Pharmacol Res 1999;19:83–88.Google Scholar
224. Lagrotteria, D, Holmes, S, Smieja, M, et al. Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea. Clin Infect Dis 2006;43:547–552.Google Scholar
225. Johnson, S, Schriever, C, Galang, M, et al. Interruption of recurrent Clostridium diffidle-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007;44:846–848.Google Scholar
226. Curry, SR, Marsh, JW, Shutt, KA, et al. High frequency of rifampin resistance identified in an epidemic Clostridium difficile clone from a large teaching hospital. Clin Infect Dis 2009;48:425–429.Google Scholar
227. Enache-Angoulvant, A, Hennequin, C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis 2005;41:1559–1568.Google Scholar
228. Dendukuri, N, Costa, V, McGregor, M, et al. Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review. CMAJ 2005;173:167–170.Google Scholar
229. Gustafsson, A, Lund-Tonnesen, S, Berstad, A, et al. Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment. Scand J Gastroenterol 1998;33:721–727.Google Scholar
230. Aas, J, Gessert, CE, Bakken, JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 2003;36:580–585.Google Scholar
231. Giannasca, PJ, Warny, M. Active and passive immunization against Clostridium difficile diarrhea and colitis. Vaccine 2004;22:848–856.Google Scholar
232. Wilcox, MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea. J Antimicrob Chemother 2004;53:882–884.Google Scholar
233. Salcedo, J, Keates, S, Pothoulakis, C, et al. Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 1997;41:366–370.Google Scholar