Clostridium difficile and Inflammatory Bowel Disease David G. Binion, M.D. Co-Director, Co Director Inflammatory Bowel Disease Center Director, Translational Inflammatory Bowel Disease Research Division of Gastroenterology, Hepatology and Nutrition UPMC Presbyterian Hospital Visiting Professor of Medicine University of Pittsburgh School of Medicine Pittsburgh,PA
I.
Background – C. difficile
II.
Impact of C. difficile on IBD
III. Diagnostic considerations C. difficile IV. Treatment considerations
I. Clostridium difficile 1930’s - Bacillus difficillis first described as part of the normal flora of neonates. 1974 - C. difficile recognized as complication of Clindamycin use. 1978 - C. difficile identified as the cause of antibiotic-associated pseudomembranous colitis in humans. Clinical syndrome may range from watery diarrhea, pain, diarrhea abdominal pain pseudo-membranous colitis, toxic megacolon, sepsis, colonic perforation and death * Hall, I. and E. O'Toole. Am J Dis Child, 1935. 48: p. 390-402.
‡Tedesco, F.J et al. Ann Intern Med, 1974. 81(4): p. 429-33.
C. difficile: Changing spectrum of clinical disease
In the past: C. difficile linked to antibiotic use. Most cases treated successfully with metronidazole Doubling of C. C difficile associated disease between 1996 - 2003. Diminished therapeutic response to metronidazole (50% failure rate with initial course of treatment).
* McDonald LC et al. Emerg Infect Dis 2006;12:409-415. ‡ Musher DM et al. Clin Infect Dis 2005;40:1586-1590.
700 C. difficile related deaths in Quebec, Canada in one year (2003-4) 400 C. difficile related deaths annually in Quebec at the present time
BI/NAP1 Epidemic strain C. difficile
Regional R i l outbreaks tb k - Pittsburgh, Pitt b h PA PA, Q Quebec, b Canada and the mid-Atlantic and southeastern U.S. C. difficile in low risk populations – young individuals, peripartum women, community dwelling and in individuals with no p to antibiotics. exposure
Muto, C.A., et al., Infect Control Hosp Epidemiol, 2005. 26(3): p. 273-80. McDonald, L.C., et al.,N Engl J Med, 2005. 353(23): p. 2433-41. 2005. MMWR Morb Mortal Wkly Rep, 2005. 54(47): p. 1201-5.
C. difficile Epidemic in U.S. BI/NAP1 C. difficile in U.S. Nov. 2007 (n = 38)
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BI/NAP1 C. difficile in U.S. Oct. 2008 IDSA Meetings
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Centers for Disease Control and Prevention. Data & Statistics about Clostridium difficile infections. www.cdc.gov/ncidod/dhqp/id_cdiff_data.html
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Current burden of C. difficile in U.S.
October 2008 – BI/NAP1 has been isolated in all 50 states (IDSA). Total number of C. difficile cases annually in U S is U.S. i >500,000. 500 000 Total number of C. difficile related deaths annually in the U.S. is >15,000.
Epidemic d is predicted d d to worsen.
Cause?
Where does the majority j y of antibiotic use occur in the U.S.?
Antibiotic use in food animal industry
Poultry industry – antibiotic use to prevent diarrheal illness
Corn fed beef require antibiotics to prevent bacterial overgrowth
BI/NAP1 Epidemic strain C. difficile and food animals
Colonization and carriage with the epidemic strain C. difficile (B1 NAP1 strain) reported in cows. C. difficile has been isolated from retail ground meat purchased in Canada.
Songer, J.G. and M.A. Anderson, Clostridium difficile: an important pathogen of food animals. Anaerobe, 2006. 12(1): p. 1-4. Rodriguez-Palacios, A., et al., Clostridium difficile in retail ground meat, Canada. Emerg Infect Dis, 2007. 13(3): p. 485-7.
C. difficile infectious inoculum is 10 spores
Poutanen SM et al. CMAJ. July 6,2004;171(1).
C. difficile: Pathogenic mechanisms 1) Antibiotic destroys normal bacterial flora
2) C. difficile grows and secretes toxins
Gut Lumen
Colonic Mucosa
3) Toxins inflame and ulcerate mucosa
4) Damaged mucosa secretes fluid causing diarrhea
Fluid secretion
Normal flora C. difficile Antibiotic Toxin PMN
Poutanen SM et al. CMAJ. July 6,2004;171(1).
Clostridium difficile
Clostridium difficile and IBD
C. difficile and IBD present in identical fashion ranging from mild diarrhea to fulminant colitis. Early studies performed 2 decades ago indicated little overlap between C. difficile and IBD. it concluded “No need for routine screening for C. C difficile in IBD population”. Recent studies: Increasing incidence and severity of C. difficile in IBD population C. difficile recentlyy identified to have a significant g negative impact on IBD morbidity.
Kochlar R et al. J Clin Gastroenterol 1993;16:26-30. Bolton RP et al. Lancet 1980;1:383-384 Trnka Y et al. Gastroenterology 1981;80:693-696.
Issa, M., et al. Clin Gastroenterol Hepatol, 2007. 5(3): p. 345-51. Rodemann, J.F., et al.Clin Gastroenterol Hepatol, 2007. 5(3): p. 339-44. Ananthakrishnan, et al. Gut, 2008. 57(2): p. 205-10.
Increasing Impact of Clostridium difficile on IBD Number of P Patients
50
40
30
20
10
0 1998 P≤.01
1999
2000
2001
2002
2003
2004
2005
Issa M et al. Clin Gastroenterol Hepatol. 2007;5: 345-51.
Increasing Proportion of Clostridium difficile Patients With IBD p=
