Clostridium difficile associated infection, diarrhea and colitis

World Journal of Gastroenterology

Volumn 15, Issue 13, 2009, Pages 1554-1580

  Hookman, Perry ^a   Barkin, Jamie S ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Clostridium difficile; Colitis; Diarrhea; Gastroenterology; Iatrogenic infection; Nosocomial infection

Indexed keywords

ANION EXCHANGE RESIN; ANTIBIOTIC AGENT; BACITRACIN; BACTERIAL VACCINE; CLOSTRIDIUM DIFFICILE TOXIN A; CLOSTRIDIUM DIFFICILE TOXIN A MONOCLONAL ANTIBODY; CLOSTRIDIUM DIFFICILE VACCINE; COLESTIPOL; COLESTYRAMINE; FUSIDIC ACID; GLUCOCORTICOID; IMMUNOGLOBULIN; IMMUNOSUPPRESSIVE AGENT; METRONIDAZOLE; MONOCLONAL ANTIBODY; NITAZOXANIDE; PLACEBO; PROBIOTIC AGENT; PROTON PUMP INHIBITOR; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RAMOPLANIN; RIFALAZIL; RIFAMPICIN; RIFAXIMIN; TEICOPLANIN; TIACUMICIN B; TINIDAZOLE; TOLEVAMER; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN; BACTERIAL PROTEIN; BACTERIAL TOXIN; ENTEROTOXIN; QUINOLONE DERIVATIVE; TCDA PROTEIN, CLOSTRIDIUM DIFFICILE; TOXB PROTEIN, CLOSTRIDIUM DIFFICILE;

ABDOMINAL CRAMP; ABSENCE OF SIDE EFFECTS; AGING; ANTIBIOTIC RESISTANCE; BACTERIAL COLONIZATION; BACTERIAL STRAIN; BACTERIAL TRANSMISSION; BACTERIAL VIRULENCE; BACTERIUM CARRIER; BIOMEDICINE; BLOOD PRESSURE; CLINICAL FEATURE; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE INFECTION; COLON RESECTION; COLONOSCOPY; COMORBIDITY; DIARRHEA; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CHOICE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG EXPOSURE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; EARLY DIAGNOSIS; ENTERITIS; ENZYME IMMUNOASSAY; FECAL BACTERIOTHERAPY; FECES MICROFLORA; GASTROINTESTINAL SURGERY; GRAFT RECIPIENT; HEART TRANSPLANTATION; HIGH RISK POPULATION; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; INFECTION CONTROL; INFECTION RISK; LABORATORY TEST; LENGTH OF STAY; MEDICAL DECISION MAKING; NAUSEA; NONHUMAN; NOSE CONGESTION; POLYMERASE CHAIN REACTION; PULSED FIELD GEL ELECTROPHORESIS; RECURRENT INFECTION; RESTRICTION MAPPING; REVIEW; SIDE EFFECT; SIGMOIDOSCOPY; TOXIC MEGACOLON; TRAVELLER DIARRHEA; UNSPECIFIED SIDE EFFECT; ANIMAL; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTION; COLITIS; DIFFERENTIAL DIAGNOSIS; DISEASE TRANSMISSION; EPIDEMIC; METABOLISM; PATHOGENICITY; PATHOPHYSIOLOGY; RISK FACTOR;

ANIMALS; BACTERIAL PROTEINS; BACTERIAL TOXINS; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTIONS; COLITIS; COMORBIDITY; DIAGNOSIS, DIFFERENTIAL; DIARRHEA; DISEASE OUTBREAKS; ENTEROTOXINS; FLUOROQUINOLONES; HUMANS; INFLAMMATORY BOWEL DISEASES; PROBIOTICS; RISK FACTORS;

EID: 64549163185     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.15.1554     Document Type: Review

References (185)

1. Hookman P, Barkin JS. Review: Clostridium difficile-associated disorders/diarrhea and Clostridium difficile colitis: the emergence of a more virulent era. Dig Dis Sci 2007; 52: 1071-1075
2. Hookman P, Barkin JS. Guidelines for prevention, surveillance, diagnosis and treatment in this new era of more virulent strains of antibiotic-associated diarrhea (AAD), Clostridium difficile-associ- ated diarrhea (CDAD) and Clostridium difficile colitis (CDAC). Pract Gastroenterol 2006; 30: 65-82
3. Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, Bourgault AM, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson TJ, Horn R, René P, Monczak Y, Dascal A. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353: 2442-2449
4. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, Johnson S, Gerding DN. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353: 2433-2441
5. Starr J. Clostridium difficile associated diarrhoea: diagnosis and treatment. BMJ 2005; 331: 498-501
6. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15: 573-581
7. Bartlett JG, Perl TM. The new Clostridium difficile - what does it mean? N Engl J Med 2005; 353: 2503-2505
8. De Andrés S, Ibánez M, Ballesteros A, Garcia B, Agud JL. Clostridium difficile colitis associated with valaciclovir. Pharm World Sci 2004; 26: 8-9
9. Blossom DB, McDonald LC. The challenges posed by reemerging Clostridium difficile infection. Clin Infect Dis 2007; 45: 222-227
10. Johal SS, Hammond J, Solomon K, James PD, Mahida YR. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004; 53: 673-677
11. Cramer JP, Burchard GD, Lohse AW. [Old dogmas and new perspectives in antibiotic-associated diarrhea] Med Klin (Munich) 2008; 103: 325-338; quiz 339-340
12. Blanckaert K, Coignard B, Grandbastien B, Astagneau P, Barbut F. [Update on Clostridium difficile infections] Rev Med Interne 2008; 29: 209-214
13. Fenger RV, Linneberg A, Tvede M, Ostergaard C. Increasing seroprevalence of Clostridium difficile in an adult Danish general population. Epidemiol Infect 2009; 137: 278-283
14. Drudy D, Harnedy N, Fanning S, Hannan M, Kyne L. Emergence and control of fluoroquinolone-resistant, toxin A-negative, toxin B-positive Clostridium difficile. Infect Control Hosp Epidemiol 2007; 28: 932-940
15. Schroeder MS. Clostridium difficile - associated diarrhea. Am Fam Physician 2005; 71: 921-928
16. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 2008; 14: 929-931
17. Pépin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 2005; 173: 1037-1042
18. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, Leblanc M, Rivard G, Bettez M, Primeau V, Nguyen M, Jacob CE, Lanthier L. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005; 41: 1254-1260
19. Kuijper EJ, Coignard B, Tüll P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006; 12 Suppl 6: 2-18
20. Simango C, Mwakurudza S. Clostridium difficile in broiler chickens sold at market places in Zimbabwe and their antimicrobial susceptibility. Int J Food Microbiol 2008; 124: 268-270
21. Koh TH, Tan AL, Tan ML, Wang G, Song KP. Epidemiology of Clostridium difficile infection in a large teaching hospital in Singapore. Pathology 2007; 39: 438-442
22. Spigaglia P, Mastrantonio P. Molecular analysis of the pathogenicity locus and polymorphism in the putative negative regulator of toxin production (TcdC) among Clostridium difficile clinical isolates. J Clin Microbiol 2002; 40: 3470-3475
23. Popoff MR, Rubin EJ, Gill DM, Boquet P. Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. Infect Immun 1988; 56: 2299-2306
24. McEllistrem MC, Carman RJ, Gerding DN, Genheimer CW, Zheng L. A hospital outbreak of Clostridium difficile disease associated with isolates carrying binary toxin genes. Clin Infect Dis 2005; 40: 265-272
25. Barbut F, Decré D, Lalande V, Burghoffer B, Noussair L, Gigandon A, Espinasse F, Raskine L, Robert J, Mangeol A, Branger C, Petit JC. Clinical features of Clostridium difficile-associated diarrhoea due to binary toxin (actin-specific ADP-ribosyltransferase)-producing strains. J Med Microbiol 2005; 54: 181-185
26. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, Frost E, McDonald LC. 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
27. Kuijper EJ, Barbut F, Brazier JS, Kleinkauf N, Eckmanns T, Lambert ML, Drudy D, Fitzpatrick F, Wiuff C, Brown DJ, Coia JE, Pituch H, Reichert P, Even J, Mossong J, Widmer AF, Olsen KE, Allerberger F, Notermans DW, Delmée M, Coignard B, Wilcox M, Patel B, Frei R, Nagy E, Bouza E, Marin M, Akerlund T, Virolainen-Julkunen A, Lyytikäinen O, Kotila S, Ingebretsen A, Smyth B, Rooney P, Poxton IR, Monnet DL. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill 2008; 13
28. Rupnik M. Clostridium difficile toxinotypes. Ljubljana: University of Ljubljana, 2006 [cited 2006 May 9]. Available from: URL: http://www.mf.uni-mb.si/Mikro/tox/
29. Rupnik M, Avesani V, Janc M, von Eichel-Streiber C, Delmée M. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol 1998; 36: 2240-2247
30. McFarland LV. Update on the changing epidemiology of Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol 2008; 5: 40-48
31. Savidge TC, Pan WH, Newman P, O'brien M, Anton PM, Pothoulakis C. Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 2003; 125: 413-420
32. Rupnik M, Dupuy B, Fairweather NF, Gerding DN, Johnson S, Just I, Lyerly DM, Popoff MR, Rood JI, Sonenshein AL, Thelestam M, Wren BW, Wilkins TD, von Eichel-Streiber C. Revised nomenclature of Clostridium difficile toxins and associated genes. J Med Microbiol 2005; 54: 113-117
33. Stabler RA, Dawson LF, Phua LT, Wren BW. Comparative analysis of BI/NAP1/027 hypervirulent strains reveals novel toxin B-encoding gene (tcdB) sequences. J Med Microbiol 2008; 57: 771-775
34. Rupnik M, Kato N, Grabnar M, Kato H. New types of toxin A-negative, toxin B-positive strains among Clostridium difficile isolates from Asia. J Clin Microbiol 2003; 41: 1118-1125
35. Drudy D, Quinn T, O'Mahony R, Kyne L, O'Gaora P, Fanning S. High-level resistance to moxifloxacin and gatifloxacin associated with a novel mutation in gyrB in toxin-A-negative, toxin-B-positive Clostridium difficile. J Antimicrob Chemother 2006; 58: 1264-1267
36. Shin BM, Kuak EY, Yoo HM, Kim EC, Lee K, Kang JO, Whang DH, Shin JH. Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005. J Med Microbiol 2008; 57: 697-701
37. Shin BM, Kuak EY, Yoo SJ, Shin WC, Yoo HM. Emerging toxin A-B+ variant strain of Clostridium difficile responsible for pseudomembranous colitis at a tertiary care hospital in Korea. Diagn Microbiol Infect Dis 2008; 60: 333-337
38. Wershil BK, Castagliuolo I, Pothoulakis C. Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. Gastroenterology 1998; 114: 956-964
39. He D, Hagen SJ, Pothoulakis C, Chen M, Medina ND, Warny M, LaMont JT. Clostridium difficile toxin A causes early damage to mitochondria in cultured cells. Gastroenterology 2000; 119: 139-150
40. Walsh SV, Hopkins AM, Chen J, Narumiya S, Parkos CA, Nusrat A. Rho kinase regulates tight junction function and is necessary for tight junction assembly in polarized intestinal epithelia. Gastroenterology 2001; 121: 566-579
41. Voth DE, Ballard JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005; 18: 247-263
42. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415: 389-395
43. Lehrer RI, Bevins CL, Ganz T. Defensins and other antimicrobial peptides. In: Mestecky J, Bienstock J, Lamm ME, Strober WM, McGhee J, Mayer L, eds. Mucosal Immunology. 3rd ed. New York: Academic Press, 2005: 95-110
44. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003; 3: 710-720
45. Maemoto A, Qu X, Rosengren KJ, Tanabe H, Henschen-Edman A, Craik DJ, Ouellette AJ. Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J Biol Chem 2004; 279: 44188-44196
46. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang JM, Howard OM, Oppenheim JJ. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525-528
47. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 2004; 22: 181-215
48. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003; 422: 522-526
49. Ouellette AJ, Bevins CL. Paneth cell defensins and innate immunity of the small bowel. Inflamm Bowel Dis 2001; 7: 43-50
50. Porter EM, Liu L, Oren A, Anton PA, Ganz T. Localization of human intestinal defensin 5 in Paneth cell granules. Infect Immun 1997; 65: 2389-2395
51. Porter EM, Bevins CL, Ghosh D, Ganz T. The multifaceted Paneth cell. Cell Mol Life Sci 2002; 59: 156-170
52. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003; 4: 269-273
53. Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 2006; 313: 1126-1130
54. Bevins CL. The Paneth cell and the innate immune response. Curr Opin Gastroenterol 2004; 20: 572-580
55. Hornef MW, Pütsep K, Karlsson J, Refai E, Andersson M. Increased diversity of intestinal antimicrobial peptides by covalent dimer formation. Nat Immunol 2004; 5: 836-843
56. Giesemann T, Guttenberg G, Aktories K. Human alpha-defensins inhibit Clostridium difficile toxin B. Gastroenterology 2008; 134: 2049-2058
57. Wang W, Mulakala C, Ward SC, Jung G, Luong H, Pham D, Waring AJ, Kaznessis Y, Lu W, Bradley KA, Lehrer RI. Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin. J Biol Chem 2006; 281: 32755-32764
58. Kim C, Slavinskaya Z, Merrill AR, Kaufmann SH. Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family. Biochem J 2006; 399: 225-229
59. Kim C, Kaufmann SH. Defensin: a multifunctional molecule lives up to its versatile name. Trends Microbiol 2006; 14: 428-431
60. Kim C, Gajendran N, Mittrucker HW, Weiwad M, Song YH, Hurwitz R, Wilmanns M, Fischer G, Kaufmann SH. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci USA 2005; 102: 4830-4835
61. Kelly CP, LaMont JT. Clostridium difficile infection. Annu Rev Med 1998; 49: 375-390
62. Lawrence SJ. Contemporary management of Clostridium difficile-associated disease. Gastroenterol Endoscopy News Spec Ed 2007; 35-40
63. Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR, Gerding DN. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117: 297-302
64. Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RL, Donskey CJ. 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
65. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320: 204-210
66. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000; 342: 390-397
67. Freeman HJ. Recent development s on the role of Clostridium difficile in inflammatory bowel disease. World J Gastroenterol 2008; 14: 2794-2796
68. Wanahita A, Goldsmith EA, Marino BJ, Musher DM. Clostridium difficile infection in patients with unexplained leukocytosis. Am J Med 2003; 115: 543-546
69. Bulusu M, Narayan S, Shetler K, Triadafilopoulos G. Leukocytosis as a harbinger and surrogate marker of Clostridium difficile infection in hospitalized patients with diarrhea. Am J Gastroenterol 2000; 95: 3137-3141
70. Triadafilopoulos G, Hallstone AE. Acute abdomen as, the first presentation of pseudomembranous colitis. Gastroenterology 1991; 101: 685-691
71. Dansinger ML, Johnson S, Jansen PC, Opstad NL, Bettin KM, Gerding DN. Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study. Clin Infect Dis 1996; 22: 932-937
72. Rybolt AH, Bennett RG, Laughon BE, Thomas DR, Greenough WB 3rd, Bartlett JG. Protein-losing enteropathy associated with Clostridium difficile infection. Lancet 1989; 1: 1353-1355
73. Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Dis Colon Rectum 1995; 38: 350-354
74. Birnbaum J, Bartlett JG, Gelber AC. Clostridium difficile: an under-recognized cause of reactive arthritis? Clin Rheumatol 2008; 27: 253-255
75. Shaikh N, Kettern MA, Hanssens Y, Elshafie SS, Louon A. A rare and unsuspected complication of Clostridium difficile infection. Intensive Care Med 2008; 34: 963-966
76. De Andrés S, Ferreiro D, Ibanez M, Ballesteros A, García B, Agud JL. Clostridium difficile colitis associated with valaciclovir. Pharm World Sci 2004; 26: 8-9
77. Yearsley KA, Gilby LJ, Ramadas AV, Kubiak EM, Fone DL, Allison MC. Proton pump inhibitor therapy is a risk factor for Clostridium difficile-associated diarrhoea. Aliment Pharmacol Ther 2006; 24: 613-619
78. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005; 294: 2989-2995
79. Cadle RM, Mansouri MD, Logan N, Kudva DR, Musher DM. Association of proton-pump inhibitors with outcomes in Clostridium difficile colitis. Am J Health Syst Pharm 2007; 64: 2359-2363
80. Jump RL, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea? Antimicrob Agents Chemother 2007; 51: 2883-2887
81. Rouphael NG, O'Donnell JA, Bhatnagar J, Lewis F, Polgreen PM, Beekmann S, Guarner J, Killgore GE, Coffman B, Campbell J, Zaki SR, McDonald LC. Clostridium difficile-associated diarrhea: an emerging threat to pregnant women. Am J Obstet Gynecol 2008; 198: 635.e1-635.e6
82. Elixhauser A (AHRQ), Jhung MA. (Centers for Disease Control and Prevention). Clostridium Difficile-Associated Disease in U.S. Hospitals, 1993-2005. HCUP Statistical Brief #50. April 2008. Agency for Healthcare Research and Quality, Rockville, MD. Available from: URL: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf
83. Kurd MF, Pulido L, Joshi A, Purtill JJ, Parvizi J. Clostridium difficile infection after total joint arthroplasty: who is at risk? J Arthroplasty 2008; 23: 839-842
84. Muñoz P, Giannella M, Alcala L, Sarmiento E, Fernandez Yañez J, Palomo J, Catalán P, Carbone J, Bouza E. Clostridium difficile-associated diarrhea in heart transplant recipients: is hypogammaglobulinemia the answer? J Heart Lung Transplant 2007; 26: 907-914
85. Stelzmueller I, Goegele H, Biebl M, Wiesmayr S, Berger N, Tabarelli W, Ruttmann E, Albright J, Margreiter R, Fille M, Bonatti H. Clostridium difficile colitis in solid organ transplantation - a single-center experience. Dig Dis Sci 2007; 52: 3231-3236
86. Kawecki D, Chmura A, Pacholczyk M, Lagiewska B, Adadynski L, Wasiak D, Malkowski P, Sawicka-Grzelak A, Rokosz A, Szymanowska A, Swoboda-Kopec E, Wroblewska M, Rowinski W, Durlik M, Paczek L, Luczak M. Detection of Clostridium difficile in stool samples from patients in the early period after liver transplantation. Transplant Proc 2007; 39: 2812-2815
87. Carignan A, Allard C, Pépin J, Cossette B, Nault V, Valiquette L. Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain. Clin Infect Dis 2008; 46: 1838-1843
88. Zerey M, Paton BL, Lincourt AE, Gersin KS, Kercher KW, Heniford BT. The burden of Clostridium difficile in surgical patients in the United States. Surg Infect (Larchmt) 2007; 8: 557-566
89. Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, Skaros S, Weber LR, Komorowski RA, Knox JF, Emmons J, Bajaj JS, Binion DG. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007; 5: 345-351
90. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care 2007; 13: 450-455
91. Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut 2008; 57: 205-210
92. Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 2007; 5: 339-344
93. Scheurer D. Diagnostic and treatment delays in recurrent Clostridium difficile-associated disease. J Hosp Med 2008; 3: 156-159
94. Fekety R, Shah AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993; 269: 71-75
95. Song HJ, Shim KN, Jung SA, Choi HJ, Lee MA, Ryu KH, Kim SE, Yoo K. Antibiotic-associated diarrhea: candidate organisms other than Clostridium difficile. Korean J Intern Med 2008; 23: 9-15
96. Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Zacherl J, Bischof G, Cosentini E, Feil W, Schiessel R, LaMont JT. Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 1995; 95: 2004-2011
97. Seppälä K, Hjelt L, Sipponen P. Colonoscopy in the diagnosis of antibiotic-associated colitis. A prospective study. Scand J Gastroenterol 1981; 16: 465-468
98. Tedesco FJ. Antibiotic associated pseudomembranous colitis with negative proctosigmoidoscopy examination. Gastroenterology 1979; 77: 295-297
99. Shen BO, Jiang ZD, Fazio VW, Remzi FH, Rodriguez L, Bennett AE, Lopez R, Queener E, Dupont HL. Clostridium difficile infection in patients with ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 2008; 6: 782-788
100. Lamontagne F, Labbé AC, Haeck O, Lesur O, Lalancette M, Patino C, Leblanc M, Laverdière M, Pépin J. 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
101. Hayetian FD, Read TE, Brozovich M, Garvin RP, Caushaj PF. Ileal perforation secondary to Clostridium difficile enteritis: report of 2 cases. Arch Surg 2006; 141: 97-99
102. Vesoulis Z, Williams G, Matthews B. Pseudomembranous enteritis after proctocolectomy: report of a case. Dis Colon Rectum 2000; 43: 551-554
103. Gooding IR, Springall R, Talbot IC, Silk DB. Idiopathic small-intestinal inflammation after colectomy for ulcerative colitis. Clin Gastroenterol Hepatol 2008; 6: 707-709
104. Lundeen SJ, Otterson MF, Binion DG, Carman ET, Peppard WJ. Clostridium difficile enteritis: an early postoperative complication in inflammatory bowel disease patients after colectomy. J Gastrointest Surg 2007; 11: 138-142
105. Tremaine WJ. Inflammatory Bowel Disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol 2007; 5: 310-311
106. Verdoorn BP, Orenstein R, Wilson JW, Estes LL, Wendt RF, Schleck CD, Harmsen WS, Nyre LM, Patel R. Effect of telephoned notification of positive Clostridium difficile test results on the time to the ordering of antimicrobial therapy. Infect Control Hosp Epidemiol 2008; 29: 658-660
107. Kuijper EJ, van Dissel JT, Wilcox MH. Clostridium difficile: changing epidemiology and new treatment options. Curr Opin Infect Dis 2007; 20: 376-383
108. Peterson LR, Manson RU, Paule SM, Hacek DM, Robicsek A, Thomson RB Jr, Kaul KL. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007; 45: 1152-1160
109. O'Connor D, Hynes P, Cormican M, Collins E, CorbettFeeney G, Cassidy M. Evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 2001; 39: 2846-2849
110. Turgeon DK, Novicki TJ, Quick J, Carlson L, Miller P, Ulness B, Cent A, Ashley R, Larson A, Coyle M, Limaye AP, Cookson BT, Fritsche TR. Six rapid tests for direct detection of Clostridium difficile and its toxins in fecal samples compared with the fibroblast cytotoxicity assay. J Clin Microbiol 2003; 41: 667-670
111. Vanpoucke H, De Baere T, Claeys G, Vaneechoutte M, Verschraegen G. Evaluation of six commercial assays for the rapid detection of Clostridium difficile toxin and/or antigen in stool specimens. Clin Microbiol Infect 2001; 7: 55-64
112. Yücesoy M, McCoubrey J, Brown R, Poxton IR. Detection of toxin production in Clostridium difficile strains by three different methods. Clin Microbiol Infect 2002; 8: 413-418
113. Killgore G, Thompson A, Johnson S, Brazier J, Kuijper E, Pepin J, Frost EH, Savelkoul P, Nicholson B, van den Berg RJ, Kato H, Sambol SP, Zukowski W, Woods C, Limbago B, Gerding DN, McDonald LC. 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 tandemrepeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. J Clin Microbiol 2008; 46: 431-437
114. Merz CS, Kramer C, Forman M, Gluck L, Mills K, Senft K, Steiman I, Wallace N, Charache P. Comparison of four commercially available rapid enzyme immunoassays with cytotoxin assay for detection of Clostridium difficile toxin(s) from stool specimens. J Clin Microbiol 1994; 32: 1142-1147
115. Altindiş M, Usluer S, Ciftçi H, Tunç N, Cetinkaya Z, Aktepe OC. [Investigation of the presence of Clostridium difficile in antibiotic associated diarrhea patients by culture and toxin detection methods] Mikrobiyol Bul 2007; 41: 29-37
116. Gerding DN, Muto CA, Owens RC Jr. Measures to control and prevent Clostridium difficile infection. Clin Infect Dis 2008; 46 Suppl 1: S43-S49
117. Modena S, Gollamudi S, Friedenberg F. Continuation of antibiotics is associated with failure of metronidazole for Clostridium difficile-associated diarrhea. J Clin Gastroenterol 2006; 40: 49-54
118. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet 1983; 2: 1043-1046
119. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. 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
120. Al-Nassir WN, Sethi AK, Nerandzic MM, Bobulsky GS, Jump RL, Donskey CJ. Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008; 47: 56-62
121. Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145: 758-764
122. Freeman J, Baines SD, Saxton K, Wilcox MH. Effect of metronidazole on growth and toxin production by epidemic Clostridium difficile PCR ribotypes 001 and 027 in a human gut model. J Antimicrob Chemother 2007; 60: 83-91
123. McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 2002; 97: 1769-1775
124. Johnson S, Schriever C, Galang M, Kelly CP, Gerding DN. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007; 44: 846-848
125. Fernandez A, Anand G, Friedenberg F. Factors associated with failure of metronidazole in Clostridium difficileassociated disease. J Clin Gastroenterol 2004; 38: 414-418
126. Kyne L, Kelly CP. Recurrent Clostridium difficile diarrhoea. Gut 2001; 49: 152-153
127. Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996; 22: 813-818
128. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev 2008; CD004611
129. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL, Noorani Z. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 271: 1913-1918
130. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol 2008; 14: 2650-2661
131. Surawicz CM, McFarland LV, Greenberg RN, Rubin M, Fekety R, Mulligan ME, Garcia RJ, Brandmarker S, Bowen K, Borjal D, Elmer GW. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000; 31: 1012-1017
132. Segarra-Newnham M. Probiotics for Clostridium difficileassociated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii. Ann Pharmacother 2007; 41: 1212-1221
133. Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol 2004; 38: 475-483
134. Borody TJ. "Flora Power" - fecal bacteria cure chronic C. difficile diarrhea. Am J Gastroenterol 2000; 95: 3028-3029
135. 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
136. Bowden TA Jr, Mansberger AR Jr, Lykins LE. Pseudomembraneous enterocolitis: mechanism for restoring floral homeostasis. Am Surg 1981; 47: 178-183
137. Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958; 44: 854-859
138. Fløtterød O, Hopen G. [Refractory Clostridium difficile infection. Untraditional treatment of antibiotic-induced colitis] Tidsskr Nor Laegeforen 1991; 111: 1364-1365
139. Gustafsson A, Lund-Tønnesen S, Berstad A, Midtvedt T, Norin E. Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment. Scand J Gastroenterol 1998; 33: 721-727
140. Lund-Tønnesen S, Berstad A, Schreiner A, Midtvedt T. [Clostridium difficile-associated diarrhea treated with homologous feces] Tidsskr Nor Laegeforen 1998; 118: 1027-1030
141. Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol 2000; 95: 3283-3285
142. Schwan A, Sjölin S, Trottestam U, Aronsson B. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of normal faeces. Scand J Infect Dis 1984; 16: 211-215
143. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989; 1: 1156-1160
144. You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med 2008; 148: 632-633
145. Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol 2003; 37: 42-47
146. McVay CS, Rolfe RD. In vitro and in vivo activities of nitazoxanide against Clostridium difficile. Antimicrob Agents Chemother 2000; 44: 2254-2258
147. Musher DM, Logan N, Hamill RJ, Dupont HL, Lentnek A, Gupta A, Rossignol JF. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis 2006; 43: 421-427
148. Pankuch GA, Appelbaum PC. Activities of tizoxanide and nitazoxanide compared to those of five other thiazolides and three other agents against anaerobic species. Antimicrob Agents Chemother 2006; 50: 1112-1117
149. Citron DM, Tyrrell KL, Warren YA, Fernandez H, Merriam CV, Goldstein EJ. In vitro activities of tinidazole and metronidazole against Clostridium difficile, Prevotella bivia and Bacteroides fragilis. Anaerobe 2005; 11: 315-317
150. Fung HB, Doan TL. Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther 2005; 27: 1859-1884
151. Gerber M, Ackermann G. OPT-80, a macrocyclic antimicrobial agent for the treatment of Clostridium difficile infections: a review. Expert Opin Investig Drugs 2008; 17: 547-553
152. Finegold SM, Molitoris D, Vaisanen ML, Song Y, Liu C, Bolaños M. In vitro activities of OPT-80 and comparator drugs against intestinal bacteria. Antimicrob Agents Chemother 2004; 48: 4898-902
153. Kokkotou E, Moss AC, Michos A, Espinoza D, Cloud JW, Mustafa N, O'Brien M, Pothoulakis C, Kelly CP. Comparative efficacies of rifaximin and vancomycin for treatment of Clostridium difficile-associated diarrhea and prevention of disease recurrence in hamsters. Antimicrob Agents Chemother 2008; 52: 1121-1126
154. Boero M, Berti E, Morgando A, Verma G. Treatment for colitis caused by Clostridium difficile: results of a randomized open study of rifaximin versus vancomycin. Microbiologia Medica 1990; 5: 74-77
155. Pullman J, Prieto J, Leach TS. Ramoplanin versus vancomycin in the treatment of Clostridium difficile diarrhea: a phase 2 study. Abstr. 44th Intersci. Conf. Antimicrob Agents Chemother, 2004: abstract K-985a
156. Taylor CP, Tummala S, Molrine D, Davidson L, Farrell RJ, Lembo A, Hibberd PL, Lowy I, Kelly CP. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A. Vaccine 2008; 26: 3404-3409
157. Hinkson PL, Dinardo C, DeCiero D, Klinger JD, Barker RH Jr. Tolevamer, an anionic polymer, neutralizes toxins produced by the BI/027 strains of Clostridium difficile. Antimicrob Agents Chemother 2008; 52: 2190-2195
158. Jank T, Ziegler MO, Schulz GE, Aktories K. Inhibition of the glucosyltransferase activity of clostridial Rho/Ras-glucosylating toxins
159. Sougioultzis S, Kyne L, Drudy D, Keates S, Maroo S, Pothoulakis C, Giannasca PJ, Lee CK, Warny M, Monath TP, Kelly CP. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 2005; 128: 764-770
160. Aronsson B, Granström M, Möllby R, Nord CE. Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. Infection 1985; 13: 97-101
161. Leung DY, Kelly CP, Boguniewicz M, Pothoulakis C, LaMont JT, Flores A. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991; 118: 633-637
162. Warny M, Vaerman JP, Avesani V, Delmee M. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun 1994; 62: 384-389
163. Kotloff KL, Wasserman SS, Losonsky GA, Thomas W Jr, Nichols R, Edelman R, Bridwell M, Monath TP. Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults. Infect Immun 2001; 69: 988-995
164. McPherson S, Rees CJ, Ellis R, Soo S, Panter SJ. Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea. Dis Colon Rectum 2006; 49: 640-645
165. Dallal RM, Harbrecht BG, Boujoukas AJ, Sirio CA, Farkas LM, Lee KK, Simmons RL. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg 2002; 235: 363-372
166. Hall JF, Berger D. Outcome of colectomy for Clostridium difficile colitis: a plea for early surgical management. Am J Surg 2008; 196: 384-388
167. Oughton MT, Miller MA. Clinical and Epidemiological Aspects of Clostridium difficile. Clin Microbiol Newsletter 2008; 30: 87-95
168. Quinn LK, Chen Y, Herwaldt LA. Infection control policies and practices for Iowa long-term care facility residents with Clostridium difficile infection. Infect Control Hosp Epidemiol 2007; 28: 1228-1232
169. Bobulsky GS, Al-Nassir WN, R iggs MM, Sethi AK, Donskey CJ. Clostridium difficile skin contamination in patients with C. difficile-associated disease. Clin Infect Dis 2008; 46: 447-450
170. Davey P, Brown E, Fenelon L, Finch R, Gould I, Hartman G, Holmes A, Ramsay C, Taylor E, Wilcox M, Wiffen P. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2005; CD003543
171. Furuno JP, Harris AD, Wright MO, Hartley DM, McGregor JC, Gaff HD, Hebden JN, Standiford HC, Perencevich EN. Value of performing active surveillance cultures on intensive care unit discharge for detection of methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol 2007; 28: 666-670
172. Siegel JD, Rhinehart E, Jackson M, Chiarello L, Healthcare Infection Control Practices Advisory Committee. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings 2007. Atlanta (GA): Centers for Disease Control and Prevention, 2007
173. Bettin K, Clabots C, Mathie P, Willard K, Gerding DN. 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
174. 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, quiz CE1-CE4
175. Boyce JM, Ligi C, Kohan C, Dumigan D, Havill NL. Lack of association between the increased incidence of Clostridium difficile-associated disease and the increasing use of alcohol-based hand rubs. Infect Control Hosp Epidemiol 2006; 27: 479-483
176. Gordin FM, Schultz ME, Huber RA, Gill JA. Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub. Infect Control Hosp Epidemiol 2005; 26: 650-653
177. Backman C, Zoutman DE, Marck PB. An integrative review of the current evidence on the relationship between hand hygiene interventions and the incidence of health care-associated infections. Am J Infect Control 2008; 36: 333-348
178. McDonald LC. Clostridium difficile: responding to a new threat from an old enemy. Infect Control Hosp Epidemiol 2005; 26: 672-675
179. Surawicz CM. Treatment of recurrent Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol 2004; 1: 32-38
180. Fawley WN, Underwood S, Freeman J, Baines SD, Saxton K, Stephenson K, Owens RC Jr, Wilcox MH. Efficacy of hospital cleaning agents and germicides against epidemic Clostridium difficile strains. Infect Control Hosp Epidemiol 2007; 28: 920-925
181. White LF, Dancer SJ, Robertson C. A microbiological evaluation of hospital cleaning methods. Int J Environ Health Res 2007; 17: 285-295
182. Wheeldon LJ, Worthington T, Lambert PA, Hilton AC, Lowden CJ, Elliott TS. Antimicrobial efficacy of copper surfaces against spores and vegetative cells of Clostridium difficile: the germination theory. J Antimicrob Chemother 2008; 62: 522-525
183. Gant VA, Wren MW, Rollins MS, Jeanes A, Hickok SS, Hall TJ. Three novel highly charged copper-based biocides: safety and efficacy against healthcare-associated organisms. J Antimicrob Chemother 2007; 60: 294-299
184. Shen EP, Surawicz CM. The changing face of Clostridium difficile: what treatment options remain? Am J Gastroenterol 2007; 102: 2789-2792
185. Muto CA, Blank MK, Marsh JW, Vergis EN, O'Leary MM, Shutt KA, Pasculle AW, Pokrywka M, Garcia JG, Posey K, Roberts TL, Potoski BA, Blank GE, Simmons RL, Veldkamp P, Harrison LH, Paterson DL. Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive "bundle" approach. Clin Infect Dis 2007; 45: 1266-1273