Narrative Review: The New Epidemic of Clostridium difficile–Associated Enteric Disease
Publication: Annals of Internal Medicine
Volume 145, Number 10
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Abstract
Antibiotic-associated diarrhea and colitis were well established soon after antibiotics became available. Early work implicated Staphylococcus aureus, but in 1978 Clostridium difficile became the established pathogen in the vast majority of cases. In the first 5 years (1978 through 1983), the most common cause was clindamycin, the standard diagnostic test was the cytotoxin assay, and standard management was to withdraw the implicated antibiotic and treat with oral vancomycin. Most patients responded well, but 25% relapsed when vancomycin was withdrawn. During the next 20 years (1983 through 2003), the most commonly implicated antibiotics were the cephalosporins, which reflected the rates of use; the enzyme immunoassay replaced the cytotoxin assay because of speed of results and technical ease of performance; and metronidazole replaced vancomycin as standard treatment, and principles of containment hospitals became infection control and antibiotic control. During the recent past (2003 to 2006), C. difficile has been more frequent, more severe, more refractory to standard therapy, and more likely to relapse. This pattern is widly distributed in the United States, Canada, and Europe and is now attributed to a new strain of C. difficile designated BI, NAP1, or ribotype 027 (which are synonymous terms). This strain appears more virulent, possibly because of production of large amounts of toxins, and fluoroquinolones are now major inducing agents along with cephalosporins, which presumably reflects newly acquired in vitro resistance and escalating rates of use. The recent experience does not change principles of management of the individual patient, but it does serve to emphasize the need for better diagnostics, early recognition, improved methods to manage severe disease and relapsing disease, and greater attention to infection control and antibiotic restraint.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Hummel RP, Altemeier WA, Hill EQ. Iatrogenic staphylococcal enterocolitis. Ann Surg. 1964;160:551-60. [PMID: 14206857]
2.
Khan MY, Hall WH. Staphylococcal enterocolitis—treatment with oral vancomycin. Ann Intern Med. 1966;65:1-8. [PMID: 5936663]
3.
Tedesco FJ, Barton RW, Alpers DH. Clindamycin-associated colitis. A prospective study. Ann Intern Med. 1974;81:429-33. [PMID: 4412460]
4.
Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J Infect Dis. 1977;136:701-5. [PMID: 915343]
5.
Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298:531-4. [PMID: 625309]
6.
Gerding DN. Disease associated with Clostridium difficile infection. Ann Intern Med. 1989;110:255-7. [PMID: 2643913]
7.
Fekety R, Shah AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA. 1993;269:71-5. [PMID: 8416409]
8.
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994;330:257-62. [PMID: 8043060]
9.
Aronsson B, Möllby R, Nord CE. Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiological data from Sweden, 1980-1982. J Infect Dis. 1985;151:476-81. [PMID: 3973405]
10.
Wiström J, Norrby SR, Myhre EB, Eriksson S, Granström G, Lagergren L, et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47:43-50. [PMID: 11152430]
11.
Karlström O, Fryklund B, Tullus K, Burman LG. A prospective nationwide study of Clostridium difficile-associated diarrhea in Sweden. The Swedish C. difficile Study Group. Clin Infect Dis. 1998;26:141-5. [PMID: 9455523]
12.
Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology. 1981;81:5-9. [PMID: 7239125]
13.
McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. 1989;320:204-10. [PMID: 2911306]
14.
Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J Jr. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995;16:459-77. [PMID: 7594392]
15.
Kim KH, Fekety R, Batts DH, Brown D, Cudmore M, Silva J Jr, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis. 1981;143:42-50. [PMID: 7217711]
16.
Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002;346:334-9. [PMID: 11821511]
17.
Bartlett JG, Taylor NS, Chang T, Dzink J. Clinical and laboratory observations in Clostridium difficile colitis. Am J Clin Nutr. 1980;33:2521-6. [PMID: 7435423]
18.
Moskovitz M, Bartlett JG. Recurrent pseudomembranous colitis unassociated with prior antibiotic therapy. Arch Intern Med. 1981;141:663-4. [PMID: 7224749]
19.
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;294:2989-95. [PMID: 16414946]
20.
Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353:2442-9. [PMID: 16322602]
21.
Jacobs A, Barnard K, Fishel R, Gradon JD. Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2001;80:88-101. [PMID: 11307591]
22.
Wanahita A, Goldsmith EA, Marino BJ, Musher DM. Clostridium difficile infection in patients with unexplained leukocytosis. Am J Med. 2003;115:543-6. [PMID: 14599633]
23.
Walker RC, Ruane PJ, Rosenblatt JE, Lyerly DM, Gleaves CA, Smith TF, et al. Comparison of culture, cytotoxicity assays, and enzyme-linked immunosorbent assay for toxin A and toxin B in the diagnosis of Clostridium difficile-related enteric disease. Diagn Microbiol Infect Dis. 1986;5:61-9. [PMID: 3086027]
24.
Borek AP, Aird DZ, Carroll KC. Frequency of sample submission for optimal utilization of the cell culture cytotoxicity assay for detection of Clostridium difficile toxin. J Clin Microbiol. 2005;43:2994-5. [PMID: 15956442]
25.
Ticehurst JR, Aird DZ, Dam LM, Borek AP, Hargrove JT, Carroll KC. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol. 2006;44:1145-9. [PMID: 16517916]
26.
Manabe YC, Vinetz JM, Moore RD, Merz C, Charache P, Bartlett JG. Clostridium difficile colitis: an efficient clinical approach to diagnosis. Ann Intern Med. 1995;123:835-40. [PMID: 7486465]
27.
van den Berg RJ, Kuijper EJ, van Coppenraet LE, Claas EC. Rapid diagnosis of toxinogenic Clostridium difficile in faecal samples with internally controlled real-time PCR. Clin Microbiol Infect. 2006;12:184-6. [PMID: 16441459]
28.
Riley TV, Bowman RA, Golledge CL. Usefulness of culture in the diagnosis of Clostridium difficile infection [Letter]. Eur J Clin Microbiol Infect Dis. 1995;14:1109-11. [PMID: 8681993]
29.
Thomas C, Riley TV. Restriction of third generation cephalosporin use reduces the incidence of Clostridium difficile-associated diarrhoea in hospitalised patients. Commun Dis Intell. 2003;27 Suppl S28-31. [PMID: 12807270]
30.
Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D, et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med. 1999;341:1645-51. [PMID: 10572152]
31.
Bartlett JG. Antimicrobial agents implicated in Clostridium difficile toxin-associated diarrhea of colitis. Johns Hopkins Med J. 1981;149:6-9. [PMID: 7253364]
32.
Bricker E, Garg R, Nelson R, Loza A, Novak T, Hansen J. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2005;:CD004610. [PMID: 15674956]
33.
Mogg GA, Keighley MR, Burdon DW, Alexander-Williams J, Youngs D, Johnson M, et al. Antibiotic-associated colitis—a review of 66 cases. Br J Surg. 1979;66:738-42. [PMID: 509051]
34.
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. Ann Intern Med. 1992;117:297-302. [PMID: 1322075]
35.
Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis. 2005;5:549-57. [PMID: 16122678]
36.
Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut. 1986;27:1169-72. [PMID: 3781329]
37.
Gerding DN. Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection? Clin Infect Dis. 1997;25 Suppl 2 S206-10. [PMID: 9310680]
38.
Peláez T, Alcalá L, Alonso R, Rodríguez-Créixems M, García-Lechuz JM, Bouza E. Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob Agents Chemother. 2002;46:1647-50. [PMID: 12019070]
39.
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;2:1043-6. [PMID: 6138597]
40.
Wenisch C, Parschalk B, Hasenhündl 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;22:813-8. [PMID: 8722937]
41.
Musher DM, Aslam S, Logan N, Nallacheru S, Bhaila I, Borchert F, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-90. [PMID: 15889354]
42.
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. [PMID: 16340634]
43.
Wilcox MH, Howe R. Diarrhoea caused by Clostridium difficile: response time for treatment with metronidazole and vancomycin. J Antimicrob Chemother. 1995;36:673-9. [PMID: 8591942]
44.
Fekety R, Silva J, Armstrong J, Allo M, Browne R, Ebright J, et al. Treatment of antibiotic-associated enterocolitis with vancomycin. Rev Infect Dis. 1981;3 suppl S273-81. [PMID: 7342291]
45.
Bartlett JG. Treatment of Clostridium difficile colitis. Gastroenterology. 1985;89:1192-5.
46.
Apisarnthanarak A, Razavi B, Mundy LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis. 2002;35:690-6. [PMID: 12203166]
47.
Johnson S, Peterson LR, Gerding DN. Intravenous metronidazole and Clostridium difficile-associated diarrhea or colitis [Letter]. J Infect Dis. 1989;160:1087-8. [PMID: 2584759]
48.
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;342:390-7. [PMID: 10666429]
49.
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;49:640-5. [PMID: 16525744]
50.
Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea. J Antimicrob Chemother. 2004;53:882-4. [PMID: 15073160]
51.
Lipsett PA, Samantaray DK, Tam ML, Bartlett JG, Lillemoe KD. Pseudomembranous colitis: a surgical disease? Surgery. 1994;116:491-6. [PMID: 8079179]
52.
Koss K, Clark MA, Sanders DS, Morton D, Keighley MR, Goh J. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis. 2006;8:149-54. [PMID: 16412077]
53.
Longo WE, Mazuski JE, Virgo KS, Lee P, Bahadursingh AN, Johnson FE. Outcome after colectomy for Clostridium difficile colitis. Dis Colon Rectum. 2004;47:1620-6. [PMID: 15540290]
54.
Fekety R, McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Mulligan ME. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997;24:324-33. [PMID: 9114180]
55.
Surawicz CM, McFarland LV, Greenberg RN, Rubin M, Fekety R, Mulligan ME, et al. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis. 2000;31:1012-7. [PMID: 11049785]
56.
Johnson S, Adelmann A, Clabots CR, Peterson LR, Gerding DN. Recurrences of Clostridium difficile diarrhea not caused by the original infecting organism. J Infect Dis. 1989;159:340-3. [PMID: 2915158]
57.
Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357:189-93. [PMID: 11213096]
58.
Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA. 1996;275:870-6. [PMID: 8596226]
59.
Dendukuri N, Costa V, McGregor M, Brophy JM. Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review. CMAJ. 2005;173:167-70. [PMID: 16027434]
60.
Lawrence SJ, Korzenik JR, Mundy LM. Probiotics for recurrent Clostridium difficile disease [Letter]. J Med Microbiol. 2005;54:905-6. [PMID: 16091446]
61.
McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002;97:1769-75. [PMID: 12135033]
62.
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;36:580-5. [PMID: 12594638]
63.
Pépin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ. 2004;171:466-72. [PMID: 15337727]
64.
Valiquette L, Low DE, Pépin J, McGeer A. Clostridium difficile infection in hospitals: a brewing storm. CMAJ. 2004;171:27-9. [PMID: 15238490]
65.
Loo VG, Libman MD, Miller MA, Bourgault AM, Frenette CH, Kelly M, et al. Clostridium difficile: a formidable foe. CMAJ. 2004;171:47-8. [PMID: 15238496]
66.
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;173:1037-42. [PMID: 16179431]
67.
Pépin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-7. [PMID: 15889355]
68.
McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433-41. [PMID: 16322603]
69.
McDonald LC. Clostridium difficile: responding to a new threat from an old enemy [Editorial]. Infect Control Hosp Epidemiol. 2005;26:672-5. [PMID: 16156321]
70.
Dallal RM, Harbrecht BG, Boujoukas AJ, Sirio CA, Farkas LM, Lee KK, et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235:363-72. [PMID: 11882758]
71.
Muto CA, Pokrywka M, Shutt K, Mendelsohn AB, Nouri K, Posey K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005;26:273-80. [PMID: 15796280]
72.
Owens RC. Clostridium difficile-associated disease: an emerging threat to patient safety: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2006;26:299-311. [PMID: 16503710]
73.
Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet. 2005;366:1079-84. [PMID: 16182895]
74.
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;36:2240-7. [PMID: 9665999]
75.
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;40:3470-5. [PMID: 12202595]
76.
Geric B, Carman RJ, Rupnik M, Genheimer CW, Sambol SP, Lyerly DM, et al. Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J Infect Dis. 2006;193:1143-50. [PMID: 16544255]
77.
Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, et al. 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;41:1254-60. [PMID: 16206099]
Comments
Sign In to Submit A CommentInformation & Authors
Information
Published In
Annals of Internal Medicine
Volume 145 • Number 10 • 21 November 2006
Pages: 758 - 764
History
Published online: 21 November 2006
Published in issue: 21 November 2006
Keywords
Copyright
© 2006 American College of Physicians.
Authors
Metrics & Citations
Metrics
Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
Download article citation data for:
Narrative Review: The New Epidemic of Clostridium difficile–Associated Enteric Disease. Ann Intern Med.2006;145:758-764. [Epub 21 November 2006]. doi:10.7326/0003-4819-145-10-200611210-00008
Narrative Review: The New Epidemic of Clostridium difficile–Associated Enteric Disease. Ann Intern Med.2006;145:758-764. [Epub 21 November 2006]. doi:10.7326/0003-4819-145-10-200611210-00008
View More
Get Access
Login Options:
Purchase
You will be redirected to acponline.org to sign-in to Annals to complete your purchase.
Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.
Create your Free Account
You will be redirected to acponline.org to create an account that will provide access to Annals.
C. difficile - a new epidemic requiring new therapeutics?
Dear Editor:
We enjoyed Dr. Bartlett's overview of the current epidemic of C. difficile, in particular his implications regarding the need for different conceptualizations of therapeutics, as well as infection control (1). The presently circulating BI/NAP1 strain of C. difficile manifests a spectrum of disease which seems, not only more severe, but in some ways qualitatively distinct from "yesterday's Cdiff."
Over the previous 4 years, we have accumulated substantial experience treating severe C. difficile-associated disease (CDAD), previously in Florida, Ohio, and currently in Los Angeles, California. Based on this experience, We wish to echo some of Dr. Bartlett's points, and wish to join with other investigators in evaluation and discussion of the following issues:
1. Rapid and sensitive diagnostic tests: it is likely that delayed diagnosis may lead to more severe morbidity with this BI/NAP1 strain. A preliminary analysis of paired stool testing for C. difficile at Florida Hospital using EIA for toxin A/B and reflex testing of negative results with cell culture-based cytotoxin assay revealed about 20% of cases EIA(- ), CDTA(+). Thus, a substantial fraction of cases can escape detection using EIA as a sole modality.
2. Therapeutic failure of oral metronidazole(monotherapy); this appears to be quite common with severe CDAD accompanied by ileus. In patients with severe disease, especially associated with peritonitis, We have had excellent results using IV metronidazole, and continuous vancomycin administered via nasogastric tube 2 grams every 24 hours. This preparation uses parenteral vancomycin mixed in 250 ml of sterile irrigant, until patient improves. Due to the frequent presence of disease in the right colon, instillation of vancomycin by enema may be suboptimal. A randomized study of such a regimen, perhaps in conjunction with other therapies seems warranted. Moreover, the mechanism of metronidazole failure remains unclear. More data regarding metronidazole pharmacokinetcs in various segments of the gut,as well as resistance, are needed.
3. Relapsing/recurrent CDAD: We have successfully treated numerous patients with pulse dosing of oral vancomycin. The construction of this regimen has been quite empiric due to a paucity of specific data in the published literature; analysis of time to sporulation and germination in the presence and absence of antibiotic pressure would be very helpful in providing a scientific basis for the high efficacy of this regimen. Better understanding of elements influencing sporulation, ecologic determinants, pathogen virulence factors (2) and host immunity is needed.
4. Adjunct immunotherapies: like other investigators (3), intravenous immunoglobulin (IVIG),using 1-2 doses of 400 mg/kg appears to have been colon and life-saving in many cases we have treated. Whether this is based on disease affecting a significantly sicker population (with poor humoral immune response to toxin), or altered immunological properties of the circulating BI/NAP1 clone is unclear.
5. Finally, it is wholly unclear whether use of drotrecogin alfa in adjunct treatment of sepsis associated with C. difficile would be of incrimental benefit in patients otherwise meeting criteria for therapy.
Until eagerly anticipated therapies such as vaccines, CDT-specific monoclonal antibodies (CDA1, MDX1388: currently in phase II trials)(4), and polymeric IgA (5) are approved, we would suggest that formal evaluation of the above modalities may be of merit.
Sincerely,
Anne M. Anglim, MD, MS Division of Infectious Diseases Keck School of Medicine-University of Southern California Los Angeles, California
(1). Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145: 758-764.
(2). Haraldsen JD, Sonenshein AL. Efficient sporulation in Clostridium difficile requires disruption of the sigmaK gene. Mol Microbiol 2003; 48: 811-821.
(3). Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea. J Antimicrob Chemother 2004; 53: 882-884.
(4). Babcock GJ, Broering TJ, Hernandez HJ, et al. Human monoclonal antibodies directed against toxin A and B prevent Clostridium difficile- induced mortality in hamsters. Infect Immun 2006; 74: 6339-6347.
(5). Stubbe H, Berdoz J, Kraebenbuhl J-P, Corthesy B. Polymeric IgA is superior to monomeric IgA and IgG carrying the same variable domain in preventing Clostridium difficile toxin A damaging of T84 monolayers. J Immunol 2000; 164: 1952-1960.
Conflict of Interest:
None declared
Hand Hygiene and C. difficile
In the infection control section of his otherwise excellent review of the epidemic strain of C. difficile, Dr. Bartlett notes that standard recommendations of the Society for Healthcare Epidemiology of America (SHEA) include, ". . . soap and water for handwashing rather than alcohol- based hand hygiene." However, the reference (1) cited is a SHEA position paper from 1995 and does not even address alcohol-based hand hygiene. Indeed, the authors reviewed the available information on hand decontamination with nondisinfectant soap versus disinfectant soap and water and conclude, ". . . the emphasis should be on compliance with the use of handwashing (with either a disinfectant or soap) until more data are available in the clinical setting to support one handwashing agent over another."
Guideline for Hand Hygiene in Health-Care Settings (2) states, "None of the agents (including alcohols, chlorhexidine, hexachlorophene, iodophors, PCMX, and triclosan) used in antiseptic handwash or antiseptic hand-rub preparations are reliably sporocidal against Clostridium spp. or Bacillus spp." The authors note that soap and water may help to physically remove spores and that use of these products (cf alcohol-based products) is "prudent" during "outbreaks of C. difficile-related infections."
As the medical director of infection control in a community hospital that has seen only sporadic cases of C. difficile, I am more concerned about preventing transmission of multi-drug resistant organisms on the hands of healthcare workers, and alcohol based products are generally felt to be superior in this regard and they have led to increased compliance. I feel we are sending our healthcare workers mixed messages without scientific support when we tell them that alcohol-based products are inferior when caring for every patient with C. difficile, as Dr. Bartlett suggests.
1. Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J Jr. Clostridium difficile-associated diarrhea and colitis. Infect Control hosp Epidemiol. 1995;16:459-77.
2. Centers for Disease Control and Prevention. Guideline for Hand Hygiene in Health-Care Settings: Recommendations of the Healthcare Infection Control Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR 2002;51(No. RR-16:[17]
Conflict of Interest:
None declared