European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Treatment guidance document for Clostridium difficile infection (CDI)

Clinical Microbiology and Infection

Volumn 15, Issue 12, 2009, Pages 1067-1079

  Bauer, M P ^a   Kuijper, E J ^a   van Dissel, J T ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Clostridium difficile; Guidelines; Treatment

Indexed keywords

ANTHELMINTIC AGENT; ANTIBIOTIC AGENT; ANTIPROTOZOAL AGENT; BACITRACIN; CREATININE; FUSIDIC ACID; LACTIC ACID; METRONIDAZOLE; NITAZOXANIDE; OPIATE; PROBIOTIC AGENT; RIFAXIMIN; TEICOPLANIN; TIGECYCLINE; VANCOMYCIN;

ANTIBIOTIC SENSITIVITY; ARTICLE; ASCITES; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE INFECTION; COLON PERFORATION; COLON RESECTION; COLONOSCOPY; CREATININE BLOOD LEVEL; DIARRHEA; DISEASE SEVERITY; DRUG ADMINISTRATION ROUTE; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG SUBSTITUTION; DRUG WITHDRAWAL; EVIDENCE BASED MEDICINE; FEVER; HEALTH PROMOTION; HEMODYNAMICS; HUMAN; IMAGE ANALYSIS; INFLAMMATION; INTESTINE DISTENSION; INTRACOLONIC DRUG ADMINISTRATION; LABORATORY TEST; LACTATE BLOOD LEVEL; LEUKOCYTE COUNT; LEUKOCYTOSIS; LOW DRUG DOSE; MICROBIOLOGY; NEUTROPHIL COUNT; PERITONITIS; PHYSICAL EXAMINATION; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGNOSIS; PSEUDOMEMBRANOUS COLITIS; RECOMMENDED DRUG DOSE; RIGOR; SIGMOIDOSCOPY; STRATEGIC PLANNING; SYMPTOMATOLOGY; TREATMENT DURATION; TREATMENT RESPONSE;

CLOSTRIDIUM DIFFICILE;

EID: 70649107673     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1111/j.1469-0691.2009.03099.x     Document Type: Article

References (81)

1. Kuijper EJ, Wilcox MW. Decreased effectiveness of metronidazole for the treatment of Clostridium difficile infection?. Clin Infect Dis 2008, 47:63-65.
2. O'Donnell LJD, Virjee J, Heaton KW. Detection of pseudodiarrhoea by simple clinical assessment of intestinal transit rate. BMJ 1990, 300:439-440.
3. McDonald LC, Coignard B, Dubberke E, Song X, Horan T, Kutty PK. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007, 28:140-145.
4. Kuijper EJ, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006, 12(suppl 6):2-18.
5. Tal S, Gurevich A, Guller V, Gurevich I, Berger D, Levi S. Risk factors for recurrence for Clostridium difficile-associated diarrhea in the elderly. Scand J Infect Dis 2002, 34:594-597.
6. 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.
7. 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.
8. Moshkowitz M, Ben-Baruch E, Kline Z, Shimoni Z, Niven M, Konikoff F. Risk factors for severity and relapse of pseudomembranous colitis in an elderly population. Colorectal Dis 2007, 9:173-177.
9. Pépin J, Alary ME, Valiquette L. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005, 40:1591-1597.
10. Nair S, Yadav D, Corpuz M, Pitchumoni CS. Clostridium difficile colitis: factors influencing treatment failure and relapse - a prospective evaluation. Am J Gastroenterol 1998, 93:1873-1876.
11. Fernandez A, Anand G, Friedenberg F. Factors asscoiated with failure of metronidazole in Clostridium difficile-associated disease. J Clin Gastroenterol 2004, 38:414-418.
12. Pépin J, Routhier S, Gagnon S, Brazeau I. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis 2006, 42:758-764.
13. Numan S, Veldkamp P, Kuijper EJ. Clostridium difficile-associated diarrhea: bovine anti-Clostridium difficile whey protein to help aid the prevention of relapses. Gut 2007, 56:888-889.
14. Warny M, Vaerman J-P, Avesani V, Delmée M. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun 1994, 62:384-389.
15. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhea. Lancet 2001, 357:189-193.
16. Al-Nassir WN, Sethi AK, Riggs MM, Bobulsky GS, Jump RLP, Donskey CJ. A comparison of clinical and microbiologic response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008, 47:56-62.
17. Louie TJ, Peppe J, Watt CK. 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.
18. Keighly MRB, Burdon DW, Arabi Y. Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea. BMJ 1978, 2:1667-1679.
19. Teasley DG, Gerding DN, Olson MM. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhoea and colitis. Lancet 1983, 2:1043-1046.
20. Young GP, Ward PB, Bayley N. Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Gastroenterology 1985, 89:1038-1045.
21. Dudley MN, McLaughlin JC, Carrington G. Oral bacitracin vs vancomycin therapy for Clostridium difficile-associated diarrhoea. A randomized double-blind trial. Arch Intern Med 1986, 146:1101-1104.
22. Fekety R, Silva J, Kauffman C. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989, 86:15-19.
23. Boero M, Berti E, Morgando A. Terapia della colite da Clostridium difficile: Risultati di uno studio randomizzato aperto rifaximina vs. vancomicina. Microbiologia Medica 1990, 5:74-77.
24. de Lalla F, Nicolin R, Rinaldi E. Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. Antimicrob Agents Chemother 1992, 36:2192-2196.
25. Wiström J. Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. Scand J Infect Dis 1994, 26:309-316.
26. Wenisch C, Parschalk B, Hasenhündl M. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996, 22:813-818.
27. Wullt M, Odenholt I. A double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium difficile-associated diarrhoea. J Antimicrob Chemother 2004, 54:211-216.
28. Musher DM, Logan N, Hamill RJ. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis 2006, 43:421-427.
29. Lagrotteria D, Holmes S, Smieja M. 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.
30. Louie T, Miller M, Donskey C, Mullane K, Goldstein EJ. Clinical outcomes, safety and pharmacokinetics of OPT-80 in a phase 2 trial of patients with Clostridium difficile infection. Antimicrob Agents Chemother 2009, 53:223-228.
31. Musher DM, Logan N, Bressler AM, Johnson DP, Rossignol JF. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clin Infect Dis 2009, 48:e41-e46.
32. Louie T, Mullane KM, Weiss K. A randomized, double-blind clinical trial of OPT-80 versus vancomycin in Clostridium difficile infection (abstract #O148). 2009, European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2009 in Helsinki, Finland
33. McFarland LV, Surawicz CM, Greenberg RN. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994, 271:1913-1918.
34. Louie TJ, Gerson M, Grimard D. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhea (CDAD). In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 17 20 September 2007, Chicago, USA. Abstract K-425a
35. Bouza E, Dryden M, Mohammed R. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhoea. In: Program and abstracts of the 18th European Congress of Clinical Microbiology and Infectious Diseases, 19 22 April 2008, Barcelona, Spain. Abstract O464
36. Lowy I. Phase II Efficacy of Human Monoclonal Antibody Treatment to Prevent C. difficile Recurrence. Oral presentation at Digestive Disease Week in Chicago on June 2, 2009; Abstract 751b
37. Bartlett JG, Tedesco FJ, Shull S. Symptomatic relapse after oral vancomycin therapy of antibiotic-associated pseudomembranous colitis. Gastroenterology 1980, 78:431-434.
38. Silva J, Batts DH, Fekety R. Treatment of Clostridium difficile colitis and diarrhea with vancomycin. Am J Med 1981, 71:815-822.
39. Cherry RD, Portnoy D, Jabbari M. Metronidazole: an alternate therapy for antibiotic-associated colitis. Gastroenterology 1982, 82:849-851.
40. Bartlett JG. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1984, 6(suppl 1):S235-S241.
41. de Lalla F, Privitera G, Rinaldi E. Treatment of Clostridium difficile-associated disease with teicoplanin. Antimicrob Agents Chemother 1989, 33:1125-1127.
42. Olson MM, Shanholtzer CJ, Lee JT, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994, 15:371-381.
43. Musher DM, Aslam S, Logan N. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 2005, 40:1586-1590.
44. Louie TJ. Treating Clostridium difficile in the future: what's coming?. Program and abstracts of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2005; Washington, DC. Abstract 1774
45. Musher DM, Logan N, Mehendiratta V. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother 2007, 59:705-710.
46. Herpers BL, Vlaminckx B, Burkhardt O. Tigecycline for severe refractory Clostridium difficile infection. Clin Infect Dis 2009, 48:1732-1735.
47. Mogg GA, George RH, Youngs D. Randomised controlled trial of colestipol in antibiotic-associated colitis. Br J Surg 1982, 69:137-139.
48. Van Dissel JT, de Groot N, Hensgens CM. Bovine antibody-enriched whey to aid in the prevention of a relapse of Clostridium difficile associated diarrhoea: preclinical and preliminary clinical data. J Med Microbiol 2005, 54:197-205.
49. Surawicz CM, McFarland LV, Greenberg RN. 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.
50. Wullt M, Hagslätt ML, Odenholt I. Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scand J Infect Dis 2003, 35:365-367.
51. Lawrence SJ, Korzenik JR, Mundy LM. Probiotics for recurrent Clostridium difficile disease. J Med Microbiol 2005, 54:905-906.
52. Mattila E, Veli-Jukka A, Broas M. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety data of a prematurely interrupted trial. Scand J Infect Dis 2008, 40:702-708.
53. Buggy BP, Fekety R, Silva J. Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomycin and rifampin. J Clin Gastroenterol 1987, 9:155-159.
54. Johnson S, Schriever C, Galang M. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007, 44:846-848.
55. Garey KW, Jiang ZD, Bellard A, DuPont HL. Rifaximin in treatment of recurrent Clostridium difficile-associated diarrhea, an uncontrolled pilot study. J Clin Gastroenterol 2009, 43:91-92.
56. Gorbach SL, Chang TW, Goldin B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 1987, 2:1519.
57. Biller JA, Katz AJ, Flores AF. Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J Pediatr Gastroenterol Nutr 1995, 21:224-226.
58. Bowden TA, Mansberger AR, Lykins LE. Pseudomembraneous enterocolitis: mechanism for restoring floral homeostasis. Am Surg 1981, 47:178-183.
59. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989, 1:1156-1160.
60. Lund-Tønnesen S, Berstad A, Schreiner A, Midtvedt T. Clostridium difficile-associated diarrhea treated with homologous feces. Tidsskr Nor Laegeforen 1998, 118:1027-1030.
61. 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.
62. Jorup-Rönström C, Håkanson A, Persson AK. Feces culture successful therapy in Clostridium difficile diarrhea. Lakartidningen 2006, 103:3603-3605.
63. Nieuwdorp M, van Nood E, Speelman P. Behandeling van recidiverende Clostridium difficile-geassocieerde diarree met een suspensie van donorfeces. Ned Tijdschr Geneeskd 2008, 152:1927-1932.
64. Macconnachie AA, Fox R, Kennedy DR, Seaton RA. Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series. QJM 2009, 102:781-784.
65. Leung DAY, Kelly CP, Boguniewicz M. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991, 118:633-637.
66. Beales IL. Intravenous immunoglobulin for recurrent Clostridium difficile diarrhoea. Gut 2002, 51:456.
67. Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea. J Antimicrob Chemother 2004, 53:882-884.
68. 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.
69. Bakken S. Novel therapies for Clostridium difficile disease. In: Program and abstracts of the 45th Annual Meeting of the Infectious Disease Society of America, 4 7 October 2007, San Diego, USA. Oral session 611
70. Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2007, DOI:
71. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. http://www.hpa.org.uk/hpr/archives/2008/news0308.htm#cdiff1, Health Protection report, 2008: 2: January 18th. Available at:
72. Baines SD, O'Connor R, Freeman J. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. J Antimicrob Chemother 2008, 62:1046-1052.
73. Nagy E, Földes J. Inactivation of metronidazole by Enterococcus faecalis. J Antimicrob Chemother 1991, 27:63-70.
74. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev 2008, DOI
75. Bassetti S, Frei R, Zimmerli W. Fungemia with Saccharomyces cerevisiae after treatment with Saccharomyces boulardii. Am J Med 1998, 105:71-72.
76. Muñoz P, Bouza E, Cuenca-Estrella M. Saccharomyces cerevisiae fungemia: an emerging infectious disease. Clin Infect Dis 2005, 40:1625-1634.
77. Besselink MG, van Santvoort HC, Buskens E. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008, 371:651-659.
78. Friedenberg F, Fernandez A, Kaul V. Intravenous metronidazole for the treatment of Clostridium difficile colitis. Dis Colon Rectum 2001, 44:1176-1180.
79. Lamontage F, Labbe AC, Kaeck O. 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.
80. Kato H, Kato H, Iwashima Y, Nakamura M, Nakamura A, Ueda R. Inappropriate use of loperamide worsens Clostridium difficile-associated diarrhoea. J Hosp Infect 2008, 70:194-195.
81. Vonberg R-P, Kuijper EJ, Wilcox MH. Infection control measures to limit the spread of Clostridium difficile. Clin Microbiol Infect 2008, 14(suppl 5):2-20.