Advertisement

The Vermiform Appendix and Recurrent Clostridium difficile Infection: A Curious Connection

Published:September 05, 2011DOI:https://doi.org/10.1016/j.cgh.2011.08.025
      Clostridium difficile is a spore-forming, anaerobic, and gram-positive bacterium that causes gastrointestinal infection resulting in diarrhea and colitis.
      • Kelly C.P.
      • LaMont J.T.
      Clostridium difficile: more difficult than ever.
      • Cohen S.H.
      • Gerding D.N.
      • Johnson S.
      • et al.
      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).
      There has been a dramatic increase in both the incidence and the severity of C difficile infection (CDI) during the past decade. Recent studies demonstrate that nosocomial CDI prolongs hospital stay, even after controlling for confounding variables such as admission diagnosis, age, and burden of comorbidities, amounting to $1–3 billion per year in extra hospital costs alone in the United States.
      • Kelly C.P.
      • Pothoulakis C.
      • LaMont J.T.
      Clostridium difficile colitis.
      • Kyne L.
      • Hamel M.B.
      • Polavaram R.
      • et al.
      Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile.
      • Vonberg R.P.
      • Reichardt C.
      • Behnke M.
      • et al.
      Costs of nosocomial Clostridium difficile-associated diarrhoea.
      The increased severity of CDI is reflected in markedly increased death rates (from 5.7 deaths per million population in 1999 to 23.7 deaths per million population in 2004), making it a leading cause of death from nosocomial infection.
      • Redelings M.D.
      • Sorvillo F.
      • Mascola L.
      Increase in Clostridium difficile-related mortality rates, United States, 1999–2004.
      Recurrence of infection is one of the most challenging aspects in the management of CDI. Approximately 25% of patients experience recurrence despite initial successful treatment. The risk might be as high as 65% for those with a history of multiple prior recurrences.
      • McFarland L.V.
      • Elmer G.W.
      • Surawicz C.M.
      Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease.
      Recurrent CDI typically occurs 1–3 weeks after completion of treatment for the initial episode, but late recurrences up to 2 months are not infrequent.
      • McFarland L.V.
      • Elmer G.W.
      • Surawicz C.M.
      Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease.
      • Do A.N.
      • Fridkin S.K.
      • Yechouron A.
      • et al.
      Risk factors for early recurrent Clostridium difficile-associated diarrhea.
      • Fekety R.
      • McFarland L.V.
      • Surawicz C.M.
      • et al.
      Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.
      • Gerding D.N.
      • Muto C.A.
      • Owens Jr, R.C.
      Treatment of Clostridium difficile infection.
      • Kyne L.
      • Kelly C.P.
      Recurrent Clostridium difficile diarrhoea.
      • Maroo S.
      • Lamont J.T.
      Recurrent Clostridium difficile.
      • McFarland L.V.
      • Surawicz C.M.
      • Rubin M.
      • et al.
      Recurrent Clostridium difficile disease: epidemiology and clinical characteristics.
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kelly C.P.
        • LaMont J.T.
        Clostridium difficile: more difficult than ever.
        N Engl J Med. 2008; 359: 1932-1940
        • Cohen S.H.
        • Gerding D.N.
        • Johnson S.
        • et al.
        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).
        Infect Control Hosp Epidemiol. 2010; 31: 431-455
        • Kelly C.P.
        • Pothoulakis C.
        • LaMont J.T.
        Clostridium difficile colitis.
        N Engl J Med. 1994; 330: 257-262
        • Kyne L.
        • Hamel M.B.
        • Polavaram R.
        • et al.
        Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile.
        Clin Infect Dis. 2002; 34: 346-353
        • Vonberg R.P.
        • Reichardt C.
        • Behnke M.
        • et al.
        Costs of nosocomial Clostridium difficile-associated diarrhoea.
        J Hosp Infect. 2008; 70: 15-20
        • Redelings M.D.
        • Sorvillo F.
        • Mascola L.
        Increase in Clostridium difficile-related mortality rates, United States, 1999–2004.
        Emerg Infect Dis. 2007; 13: 1417-1419
        • McFarland L.V.
        • Elmer G.W.
        • Surawicz C.M.
        Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease.
        Am J Gastroenterol. 2002; 97: 1769-1775
        • Do A.N.
        • Fridkin S.K.
        • Yechouron A.
        • et al.
        Risk factors for early recurrent Clostridium difficile-associated diarrhea.
        Clin Infect Dis. 1998; 26: 954-959
        • Fekety R.
        • McFarland L.V.
        • Surawicz C.M.
        • et al.
        Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.
        Clin Infect Dis. 1997; 24: 324-333
        • Gerding D.N.
        • Muto C.A.
        • Owens Jr, R.C.
        Treatment of Clostridium difficile infection.
        Clin Infect Dis. 2008; 46: S32-S42
        • Kyne L.
        • Kelly C.P.
        Recurrent Clostridium difficile diarrhoea.
        Gut. 2001; 49: 152-153
        • Maroo S.
        • Lamont J.T.
        Recurrent Clostridium difficile.
        Gastroenterology. 2006; 130: 1311-1316
        • McFarland L.V.
        • Surawicz C.M.
        • Rubin M.
        • et al.
        Recurrent Clostridium difficile disease: epidemiology and clinical characteristics.
        Infect Control Hosp Epidemiol. 1999; 20: 43-50
        • Louie T.J.
        • Miller M.A.
        • Mullane K.M.
        • et al.
        Fidaxomicin versus vancomycin for Clostridium difficile infection.
        N Engl J Med. 2011; 364: 422-431
        • Hu M.Y.
        • Katchar K.
        • Kyne L.
        • et al.
        Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection.
        Gastroenterology. 2009; 136: 1206-1214
        • Garey K.W.
        • Sethi S.
        • Yadav Y.
        • et al.
        Meta-analysis to assess risk factors for recurrent Clostridium difficile infection.
        J Hosp Infect. 2008; 70: 298-304
        • Kyne L.
        • Warny M.
        • Qamar A.
        • et al.
        Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea.
        Lancet. 2001; 357: 189-193
        • Im G.Y.
        • Modayil R.J.
        • Lin C.T.
        • et al.
        The appendix may protect against Clostridium difficile recurrence.
        Clin Gastroenterol Hepatol. 2011; 9: 1072-1077
        • Bollinger R.R.
        • Barbas A.S.
        • Bush E.L.
        • et al.
        Biofilms in the normal human large bowel: fact rather than fiction.
        Gut. 2007; 56: 1481-1482
        • Sonnenburg J.L.
        • Angenent L.T.
        • Gordon J.I.
        Getting a grip on things: how do communities of bacterial symbionts become established in our intestine?.
        Nat Immunol. 2004; 5: 569-573
        • Allen A.
        • Pearson J.P.
        The gastrointestinal adherent mucous gel barrier.
        Methods Mol Biol. 2000; 125: 57-64
        • Atuma C.
        • Strugala V.
        • Allen A.
        • et al.
        The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo.
        Am J Physiol Gastrointest Liver Physiol. 2001; 280: G922-G929
        • Palestrant D.
        • Holzknecht Z.E.
        • Collins B.H.
        • et al.
        Microbial biofilms in the gut: visualization by electron microscopy and by acridine orange staining.
        Ultrastruct Pathol. 2004; 28: 23-27
        • Randal Bollinger R.
        • Barbas A.S.
        • Bush E.L.
        • et al.
        Biofilms in the large bowel suggest an apparent function of the human vermiform appendix.
        J Theor Biol. 2007; 249: 826-831
        • Kelly C.P.
        • Kyne L.
        The host immune response to Clostridium difficile.
        J Med Microbiol. 2011; 60: 1070-1079
        • Bollinger R.R.
        • Everett M.L.
        • Wahl S.D.
        • et al.
        Secretory IgA and mucin-mediated biofilm formation by environmental strains of Escherichia coli: role of type 1 pili.
        Mol Immunol. 2006; 43: 378-387
        • Bollinger R.R.
        • Everett M.L.
        • Palestrant D.
        • et al.
        Human secretory immunoglobulin A may contribute to biofilm formation in the gut.
        Immunology. 2003; 109: 580-587
        • Orndorff P.E.
        • Devapali A.
        • Palestrant S.
        • et al.
        Immunoglobulin-mediated agglutination of and biofilm formation by Escherichia coli K-12 require the type 1 pilus fiber.
        Infect Immun. 2004; 72: 1929-1938
        • Friman V.
        • Adlerberth I.
        • Connell H.
        • et al.
        Decreased expression of mannose-specific adhesins by Escherichia coli in the colonic microflora of immunoglobulin A-deficient individuals.
        Infect Immun. 1996; 64: 2794-2798
        • Wold A.E.
        • Adlerberth I.
        Breast feeding and the intestinal microflora of the infant: implications for protection against infectious diseases.
        Adv Exp Med Biol. 2000; 478: 77-93
        • Andersson R.E.
        • Olaison G.
        • Tysk C.
        • et al.
        Appendectomy and protection against ulcerative colitis.
        N Engl J Med. 2001; 344: 808-814
        • Järnerot G.
        • Andersson M.
        • Franzén L.
        Laparoscopic appendectomy in patients with refractory ulcerative colitis.
        Gastroenterology. 2001; 120: 1562-1563
        • Jo Y.
        • Matsumoto T.
        • Yada S.
        • et al.
        Histological and immunological features of appendix in patients with ulcerative colitis.
        Dig Dis Sci. 2003; 48: 99-108
        • Okazaki K.
        • Onodera H.
        • Watanabe N.
        • et al.
        A patient with improvement of ulcerative colitis after appendectomy.
        Gastroenterology. 2000; 119: 502-506
        • Lowy I.
        • Molrine D.C.
        • Leav B.A.
        • et al.
        Treatment with monoclonal antibodies against Clostridium difficile toxins.
        N Engl J Med. 2010; 362: 197-205

      Linked Article

      • The Appendix May Protect Against Clostridium difficile Recurrence
        Clinical Gastroenterology and HepatologyVol. 9Issue 12
        • Preview
          Several risk factors have been identified for the development of recurrent Clostridium difficile infection (CDI) that alter host immunity and disrupt colonic flora. Although the function of the appendix has been debated, its active, gut-associated lymphoid tissue and biofilm production indicate potential roles in recovery from initial CDI and protection against recurrent CDI. We investigated whether the presence or absence of an appendix is associated with CDI recurrence.
        • Full-Text
        • PDF