FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 342:390-397 February 10, 2000 Number 6 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Clostridium difficile infection can result in asymptomatic carriage, mild diarrhea, or fulminant pseudomembranous colitis. We studied whether antibody responses to C. difficile toxins affect the risks of colonization, diarrhea, and asymptomatic carriage.

Methods We prospectively studied C. difficile infections in hospitalized patients who were receiv-ing antibiotics. Serial stool samples were tested for C. difficile colonization by cytotoxin assay and culture. Serum antibody (IgA, IgG, and IgM) levels and fecal antibody (IgA and IgG) levels against C. difficile toxin A, toxin B, and nontoxin antigens were measured by an enzyme-linked immunosorbent assay (ELISA).

Results Of 271 patients, 37 (14 percent) were colonized with C. difficile at the time of admission, 18 of whom were asymptomatic carriers. An additional 47 patients (17 percent) became infected in the hospital, 19 of whom remained asymptomatic. The base-line antibody levels were similar in the patients who later became colonized and those who did not. After colonization, those who became asymptomatic carriers had significantly greater increases in serum levels of IgG antibody against toxin A than did the patients in whom C. difficile diarrhea developed (P<0.001). The adjusted odds ratio for diarrhea was 48.0 (95 percent confidence interval, 3.4 to 678) among patients with colonization who had a serum level of IgG antibody against toxin A of 3.00 ELISA units or less, as compared with patients with colonization who had a level of more than 3.00 ELISA units.

Conclusions We find no evidence of immune protection against colonization by C. difficile. Howev-er, after colonization there is an association between a systemic anamnestic response to toxin A, as evidenced by increased serum levels of IgG antibody against toxin A, and asymptomatic carriage of C. difficile.

Source Information

From the Divisions of Gerontology (L.K.) and Gastroenterology (M.W., A.Q., C.P.K.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.

Address reprint requests to Dr. Kelly at the Gastroenterology Division, Dana 601, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, or at ciaran_kelly{at}caregroup.harvard.edu.

Full Text of this Article

This article has been cited by other articles:

• Lawley, T. D., Clare, S., Walker, A. W., Goulding, D., Stabler, R. A., Croucher, N., Mastroeni, P., Scott, P., Raisen, C., Mottram, L., Fairweather, N. F., Wren, B. W., Parkhill, J., Dougan, G. (2009). Antibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts. Infect. Immun. 77: 3661-3669 [Abstract] [Full Text]  
• Williams, O. M., Spencer, R. C. (2009). The management of Clostridium difficile infection. Br Med Bull 91: 87-110 [Abstract] [Full Text]  
• He, X., Sun, X., Wang, J., Wang, X., Zhang, Q., Tzipori, S., Feng, H. (2009). Antibody-Enhanced, Fc Gamma Receptor-Mediated Endocytosis of Clostridium difficile Toxin A. Infect. Immun. 77: 2294-2303 [Abstract] [Full Text]  
• Kelly, C. P. (2009). A 76-Year-Old Man With Recurrent Clostridium difficile-Associated Diarrhea: Review of C difficile Infection. JAMA 301: 954-962 [Abstract] [Full Text]  
• Saxton, K., Baines, S. D., Freeman, J., O'Connor, R., Wilcox, M. H. (2009). Effects of Exposure of Clostridium difficile PCR Ribotypes 027 and 001 to Fluoroquinolones in a Human Gut Model. Antimicrob. Agents Chemother. 53: 412-420 [Abstract] [Full Text]  
• Blondeau, J. M. (2009). What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea?. J Antimicrob Chemother 63: 238-242 [Abstract] [Full Text]  
• Kelly, C. P., LaMont, J. T. (2008). Clostridium difficile -- More Difficult Than Ever. NEJM 359: 1932-1940 [Full Text]  
• Dupuy, B., Govind, R., Antunes, A., Matamouros, S. (2008). Clostridium difficile toxin synthesis is negatively regulated by TcdC. J Med Microbiol 57: 685-689 [Abstract] [Full Text]  
• Sanchez-Hurtado, K., Corretge, M., Mutlu, E., McIlhagger, R., Starr, J. M., Poxton, I. R. (2008). Systemic antibody response to Clostridium difficile in colonized patients with and without symptoms and matched controls. J Med Microbiol 57: 717-724 [Abstract] [Full Text]  
• Brun, P., Scarpa, M., Grillo, A., Palu, G., Mengoli, C., Zecconi, A., Spigaglia, P., Mastrantonio, P., Castagliuolo, I. (2008). Clostridium difficile TxAC314 and SLP-36kDa enhance the immune response toward a co-administered antigen. J Med Microbiol 57: 725-731 [Abstract] [Full Text]  
• Wright, A., Drudy, D., Kyne, L., Brown, K., Fairweather, N. F. (2008). Immunoreactive cell wall proteins of Clostridium difficile identified by human sera. J Med Microbiol 57: 750-756 [Abstract] [Full Text]  
• Halsey, J. (2008). Current and future treatment modalities for Clostridium difficile-associated disease. Am J Health Syst Pharm 65: 705-715 [Abstract] [Full Text]  
• Fawley, W. N., Freeman, J., Smith, C., Harmanus, C., van den Berg, R. J., Kuijper, E. J., Wilcox, M. H. (2008). Use of Highly Discriminatory Fingerprinting to Analyze Clusters of Clostridium difficile Infection Cases Due to Epidemic Ribotype 027 Strains. J. Clin. Microbiol. 46: 954-960 [Abstract] [Full Text]  
• Blossom, D. B., Lewis, F. M.T., McDonald, L. C. (2008). The Changing Spectrum of Clostridium Difficile Associated Disease: Implications for Dentistry. Journal of the American Dental Association 139: 42-47 [Abstract] [Full Text]  
• Emerson, C. R. (2007). Clostridium difficile Associated Diarrhea, an Emerging Epidemic: Therapeutic Options. Journal of Pharmacy Practice 20: 347-353 [Abstract]  
• Ghose, C., Kalsy, A., Sheikh, A., Rollenhagen, J., John, M., Young, J., Rollins, S. M., Qadri, F., Calderwood, S. B., Kelly, C. P., Ryan, E. T. (2007). Transcutaneous Immunization with Clostridium difficile Toxoid A Induces Systemic and Mucosal Immune Responses and Toxin A-Neutralizing Antibodies in Mice. Infect. Immun. 75: 2826-2832 [Abstract] [Full Text]  
• Jodlowski, T. Z, Oehler, R., Kam, L. W, Melnychuk, I. (2006). Emerging Therapies in the Treatment of Clostridium difficile-Associated Disease. The Annals of Pharmacotherapy 40: 2164-2169 [Abstract] [Full Text]  
• Surowiec, D., Kuyumjian, A. G, Wynd, M. A, Cicogna, C. E (2006). Past, Present, and Future Therapies for Clostridium difficile-Associated Disease. The Annals of Pharmacotherapy 40: 2155-2163 [Abstract] [Full Text]  
• Bartlett, J. G. (2006). Narrative Review: The New Epidemic of Clostridium difficile-Associated Enteric Disease.. ANN INTERN MED 145: 758-764 [Abstract] [Full Text]  
• Babcock, G. J., Broering, T. J., Hernandez, H. J., Mandell, R. B., Donahue, K., Boatright, N., Stack, A. M., Lowy, I., Graziano, R., Molrine, D., Ambrosino, D. M., Thomas, W. D. Jr. (2006). Human Monoclonal Antibodies Directed against Toxins A and B Prevent Clostridium difficile-Induced Mortality in Hamsters. Infect. Immun. 74: 6339-6347 [Abstract] [Full Text]  
• Asha, N. J., Tompkins, D., Wilcox, M. H. (2006). Comparative Analysis of Prevalence, Risk Factors, and Molecular Epidemiology of Antibiotic-Associated Diarrhea Due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus.. J. Clin. Microbiol. 44: 2785-2791 [Abstract] [Full Text]  
• Cavalcante, I. C., Castro, M. V., Barreto, A. R. F., Sullivan, G. W., Vale, M., Almeida, P. R. C., Linden, J., Rieger, J. M., Cunha, F. Q., Guerrant, R. L., Ribeiro, R. A., Brito, G. A. C. (2006). Effect of Novel A2A Adenosine Receptor Agonist ATL 313 on Clostridium difficile Toxin A-Induced Murine Ileal Enteritis.. Infect. Immun. 74: 2606-2612 [Abstract] [Full Text]  
• Akerlund, T., Svenungsson, B., Lagergren, A., Burman, L. G. (2006). Correlation of Disease Severity with Fecal Toxin Levels in Patients with Clostridium difficile-Associated Diarrhea and Distribution of PCR Ribotypes and Toxin Yields In Vitro of Corresponding Isolates. J. Clin. Microbiol. 44: 353-358 [Abstract] [Full Text]  
• Murphy, C., Vernon, M., Cullen, M. (2006). Intravenous immunoglobulin for resistant Clostridium difficile infection. Age Ageing 35: 85-86 [Abstract] [Full Text]  
• Lemee, L., Bourgeois, I., Ruffin, E., Collignon, A., Lemeland, J.-F., Pons, J.-L. (2005). Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile. Microbiology 151: 3171-3180 [Abstract] [Full Text]  
• Pechine, S., Gleizes, A., Janoir, C., Gorges-Kergot, R., Barc, M.-C., Delmee, M., Collignon, A. (2005). Immunological properties of surface proteins of Clostridium difficile. J Med Microbiol 54: 193-196 [Abstract] [Full Text]  
• Johal, S S, Lambert, C P, Hammond, J, James, P D, Borriello, S P, Mahida, Y R (2004). Colonic IgA producing cells and macrophages are reduced in recurrent and non-recurrent Clostridiumdifficile associated diarrhoea. J. Clin. Pathol. 57: 973-979 [Abstract] [Full Text]  
• Pepin, J., Valiquette, L., Alary, M.-E., Villemure, P., Pelletier, A., Forget, K., Pepin, K., Chouinard, D. (2004). Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 171: 466-472 [Abstract] [Full Text]  
• Dial, S., Alrasadi, K., Manoukian, C., Huang, A., Menzies, D. (2004). Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 171: 33-38 [Abstract] [Full Text]  
• Poutanen, S. M., Simor, A. E. (2004). Clostridium difficile-associated diarrhea in adults. CMAJ 171: 51-58 [Abstract] [Full Text]  
• Johal, S S, Hammond, J, Solomon, K, James, P D, Mahida, Y R (2004). Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 53: 673-677 [Abstract] [Full Text]  
• Aboudola, S., Kotloff, K. L., Kyne, L., Warny, M., Kelly, E. C., Sougioultzis, S., Giannasca, P. J., Monath, T. P., Kelly, C. P. (2003). Clostridium difficile Vaccine and Serum Immunoglobulin G Antibody Response to Toxin A. Infect. Immun. 71: 1608-1610 [Abstract] [Full Text]  
• Hurley, B. W., Nguyen, C. C. (2002). The Spectrum of Pseudomembranous Enterocolitis and Antibiotic-Associated Diarrhea. Arch Intern Med 162: 2177-2184 [Abstract] [Full Text]  
• Morris, A. M., Jobe, B. A., Stoney, M., Sheppard, B. C., Deveney, C. W., Deveney, K. E. (2002). Clostridium difficile Colitis: An Increasingly Aggressive Iatrogenic Disease?. Arch Surg 137: 1096-1100 [Abstract] [Full Text]  
• Calabi, E., Fairweather, N. (2002). Patterns of Sequence Conservation in the S-Layer Proteins and Related Sequences in Clostridium difficile. J. Bacteriol. 184: 3886-3897 [Abstract] [Full Text]  
• Bartlett, J. G. (2002). Antibiotic-Associated Diarrhea. NEJM 346: 334-339 [Full Text]  
• PHILLIPS, C (2001). Serum antibody responses to Clostridium difficile toxin A: predictive and protective?. Gut 49: 167-168 [Full Text]  
• Kyne, L, Kelly, C P (2001). Recurrent Clostridium difficile diarrhoea. Gut 49: 152-153 [Full Text]  
• DRUDY, D., O'DONOGHUE, D.P., BAIRD, A., FENELON, L., O'FARRELLY, C. (2001). Flow cytometric analysis of Clostridium difficile adherence to human intestinal epithelial cells. J Med Microbiol 50: 526-534 [Abstract] [Full Text]  
• Mylonakis, E., Ryan, E. T., Calderwood, S. B. (2001). Clostridium difficile-Associated Diarrhea: A Review. Arch Intern Med 161: 525-533 [Abstract] [Full Text]  
• Kotloff, K. L., Wasserman, S. S., Losonsky, G. A., Thomas, W. Jr., Nichols, R., Edelman, R., Bridwell, M., Monath, T. P. (2001). Safety and Immunogenicity of Increasing Doses of a Clostridium difficile Toxoid Vaccine Administered to Healthy Adults. Infect. Immun. 69: 988-995 [Abstract] [Full Text]