Intervention Review

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Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

  1. Richard L Nelson1,*,
  2. Philippa Kelsey2,
  3. Hayley Leeman2,
  4. Naomi Meardon2,
  5. Haymesh Patel2,
  6. Kim Paul2,
  7. Richard Rees2,
  8. Ben Taylor2,
  9. Elizabeth Wood2,
  10. Rexanna Malakun3

Editorial Group: Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group

Published Online: 7 SEP 2011

Assessed as up-to-date: 12 OCT 2010

DOI: 10.1002/14651858.CD004610.pub4

How to Cite

Nelson RL, Kelsey P, Leeman H, Meardon N, Patel H, Paul K, Rees R, Taylor B, Wood E, Malakun R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD004610. DOI: 10.1002/14651858.CD004610.pub4.

Author Information

  1. 1

    Northern General Hospital, Department of General Surgery, Sheffield, Yorkshire, UK

  2. 2

    University of Sheffield, The Medical School, Sheffield, UK

  3. 3

    University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield, UK

*Richard L Nelson, Department of General Surgery, Northern General Hospital, Herries Road, Sheffield, Yorkshire, S5 7AU, UK.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 SEP 2011



References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Anonymous 1994 {published data only}
  • Anonymous. Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group. Scandinavian Journal of Infectious Diseases 1994;26(3):309-16. [PUBMED: 7939431]
Boero 1990 {published data only}
  • Boero M, Berti E, Morgando A, Verme G. Treatment of pseudomembranous colitis: a randomized controlled trial with rifaximin vs vancomycin [Terapia della colite da Clostridium difficile: risultati di uno studio randomizzato aperto rifaximina vs. vancomicina]. Microbiologia Medica 1990;5(2):74-7.
de Lalla 1992 {published data only}
  • de Lalla F, Nicolin R, Rinaldi E, Scarpellini P, Rigoli R, Manfrin V, et al. Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. Antimicrobial Agents and Chemotherapy 1992;36(10):2192-6. [PUBMED: 1444298]
Dudley 1986 {published data only}
  • Dudley MN, McLaughlin JC, Carrington G, Frick J, Nightingale CH, Quintiliani R. Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial. Archives of Internal Medicine 1986;146(6):1101-4. [PUBMED: 3521518]
Fekety 1989 {published data only}
  • Fekety R, Silva J, Kauffman C, Buggy B, Deery HG. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. American Journal of Medicine 1989;86(1):15-9. [PUBMED: 2910090]
Keighley 1978 {published data only}
  • Keighley MR, Burdon DW, Arabi Y, Williams JA, Thompson H, Youngs D, et al. Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea. British Medical Journal 1978;2(6153):1667-9. [PUBMED: 367509]
Lagrotteria 2006 {published data only}
  • Lagrottereria D, Holmes S, Smieja M, Smaill F, Lee C. Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea. Clinical Infectious Diseases 2006;43(5):547-52. [PUBMED: 16886144]
Louie 2009 {published data only}
  • Louie T, Miller M, Donskey C, Mullane K, Goldstein EJ. Clinical outcomes, safety and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection. Antimicrobial Agents and Chemotherapy 2009;53(1):223-8. [PUBMED: 18955525]
Musher 2006 {published data only}
  • Musher DM, Logan N, Hamill RJ, Dupont HL, Lentnek A, Gupta A, et al. Nitazoxanide for the treatment of Clostridium difficule colitis. Clinical Infectious Diseases 2006;43(4):421-7. [PUBMED: 16838229]
Musher 2009 {published data only}
  • Musher DM, Logan N, Bressler AM, Johnson DP, Rossignol JF. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clinical Infectious Diseases 2009;48(4):e41-6. [PUBMED: 19133801]
Teasley 1983 {published data only}
  • Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet 1983;2(8358):1043-6. [PUBMED: 6138597]
Wenisch 1996 {published data only}
  • 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. Clinical Infectious Diseases 1996;22(5):813-8. [PUBMED: 8722937]
Wullt 2004 {published data only}
  • 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. Journal of Antimicrobial Chemotherapy 2004;54(1):211-6. [PUBMED: 15163651]
Young 1985 {published data only}
  • Young GP, Ward PB, Bayley N, Gordon D, Higgins G, Trapani JA, et al. Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Gastroenterology 1985;89(5):1038-45. [PUBMED: 4043661]
Zar 2007 {published and unpublished data}
  • 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. Clinical Infectious Diseases 2007;45(3):302-7. [PUBMED: 17599306]

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Johnson 1992 {published data only}
  • Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR, et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Annals of Internal Medicine 1992;117(4):297-302. [PUBMED: 1322075]
Louie 2006 {published data only}
  • Louie TJ, Peppe J, Watt CK, Johnson D, Mohammed R, Dow G, et al. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea. Clinical Infectious Diseases 2006;43(4):411-20. [PUBMED: 16838228]
Lowy 2010 {published data only}
  • Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, et al. Treatment with monoclonal antibodies against clostridium difficile toxins. New England Journal of Medicine 2010;362(3):197-205. [PUBMED: 20089970]
Mattila 2008 {published data only}
  • Mattila E, Anttila VJ, Broas M, Marttila H, Poukka P, Kuusisto K, et al. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety of a prematurely interrupted trial. Scandinavian Journal of Infectious Diseases 2008;40(9):702-8. [PUBMED: 19086244]
McFarland 2002 {published data only}
  • McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. American Journal of Gastroenterology 2002;97(7):1769-75. [PUBMED: 12135033]
    Direct Link:
Noren 2006 {published data only}
  • Noren T, Wullt M, Akerlund T, Back E, Odenholt I, Burman LG. Frequent emergence of resistance in Clostridium difficile during treatment of C. difficile-associated diarrhea with fusidic acid. Antimicrobial Agents and Chemotherapy 2006;50(9):3028-32. [PUBMED: 16940098]
Numan 2007 {published data only}
  • Numan SC, Veldkamp P, Kuijper EJ, van den Berg RJ, van Dissel JT. Clostridium difficile-associated diarrhoea: bovine anti-Clostridium difficile whey protein to help aid the prevention of relapses. Gut 2007;56(6):888-9. [PUBMED: 17519495]

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Assmann 2000
Baker 2002
  • Baker SG, Kramer BS. The transitive fallacy for randomized trials: if A bests B and B bests C in separate trials, is A better than C?. BMC Medical Research Methodology 2002;2:13.
Bartlett 1980
  • Bartlett JG, Taylor NS, Chang T, Dzink J. Clinical and laboratory observations in Clostridium difficile colitis. American Journal of Clinical Nutrition 1980;33(11 Suppl):2521-6.
Bartlett 1990
Bartlett 2002
Bauer 2009
Bishara 2007
BNF 2004
  • Joint Formulary Committee. British National Formulary. 7th Edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 2004.
Bowden 1981
  • Bowden TA Jr, Mansberger AR Jr, Lykins LE. Pseudomembranous enterocolitis: mechanism for restoring floral homeostasis. American Surgeon 1981;47(4):178-83.
Cohen 2010
  • Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilkox MH. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update for the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infection Control and Hospital Epidemiology 2010;31(5):431-55.
Fekety 1993
Fekety 1997
  • Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. American Journal of Gastroenterology 1997;92(5):739-50.
George 1982
  • George WL, Rolfe RD, Finegold SM. Clostridium difficile and its cytotoxin in feces of patients with antimicrobial agent-associated diarrhea and miscellaneous conditions. Journal of Clinical Microbiology 1982;15(6):1049-53.
Gerding 1995
Higgins 2008
  • Higgins JPT, Altman DG (editors). Chapter 8: Assessing risk of bias in included studies.. In: Higgins JPT, Green S, editors(s) editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. Available from
Ho 1996
  • Ho M, Yang D, Wyle FA, Mulligan ME. Increased incidence of Clostridium difficile-associated diarrhea following decreased restriction of antibiotic use. Clinical Infectious Diseases 1996;23 Suppl 1:S102-6.
Hopkins 2009
  • Johns Hopkins. Teicoplanin. 2009.
HPA 2008
  • Health Protection Agency of the Department of Health, UK. Clostridium difficile infection: How to deal with the problem. 2008, issue 12.
HPA 2010
  • Health Protection Agency. Summary Points on Clostridium difficile infection (CDI). 2010.
Karas 2010
Kelly 1994
Khoruts 2010
  • Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Journal of Clinical Gastroenterology 2010;44(5):354-60.
Lai 1997
  • Lai KK, Melvin ZS, Menard MJ, Kotilainen HR, Baker S. Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control. Infection Control and Hospital Epidemiology 1997;18(9):628-32.
Laurence 2006
  • Laurence J. Deaths from "dirty hospital bug" double in five years. The Independant 26 May, 2006:11.
Louie 2005
Manian 1995
McDonald 2005
  • McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. New England Journal of Medicine 2005;353(23):2433-41.
McFarland 1995
  • McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, et al. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. American Journal of Gastroenterology 1995;90(3):439-48.
McFarland 1999
  • McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infection Control and Hospital Epidemiology 1999;20(1):43-50.
Morris 2002
  • Morris AM, Jobe BA, Stoney M, Sheppard BC, Deveney CW, Deveney KE. Clostridium difficile colitis: an increasingly aggressive iatrogenic disease?. Archives of Surgery 2002;137(10):1096-100.
Mosby 2003
  • Mosby. Mosby's Drug Consult 2004, 14th Edition. St. Louis, MO: Mosby, 2003.
Novell 2010
Olson 1994
  • Olson MM, Shanholtzer CJ, Lee JT Jr, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infection Control and Hospital Epidemiology 1994;15(6):371-81.
Pepin 2005
  • Pepin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. Canadian Medical Association Journal 2005;173(9):1037-42.
Pindera 2004
Privitera 1991
  • Privitera G, Scarpellini P, Ortisi G, Nicastro G, Nicolin R, de Lalla F. Prosepctive study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery. Antimicrobial Agents and Chemotherapy 1991;35(1):208-10.
Redelings 2007
Rubin 1995
Sougioultzis 2005
  • Sougioultzis S, Kyne L, Drudy D, Keates S, Maroo S, Pothoulakis C, et al. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 2005;128(3):764-70.
Thomas 2003
  • Thomas C, Stevenson M, Riley TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. Journal of Antimicrobial Chemotherapy 2003;51(6):1339-50.