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Asymptomatic carrier
Ingestion
Diarrhea
Colitis
Pseudomembranous Colitis
Colonization
Source: http://www.sickchirpse.com/wp-content/uploads/2013/01/C.-difficile.jpg
Bacteremia
Fulminant Colitis
Regulation
1) Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections. Am J Gastroenterol. Forthcoming 2013 Feb 26.
2) Fogliaa G, Shaha S, Luxemburgerb C, Pietrobona PJF. Clostridium difficile: Development of a novel candidate vaccine. Vaccine. 2012 June 19;30(29):4307-4309.
3) Rebeaud F, Bachmann MF. Immunization strategies for Clostridium difficile infections. Expert Review of Vaccines. 2012 April;11(4):469-479.
4) Soares GMS, Figueiredo LC, Faveri M, Cortelli SC, Duarte PM, Feres M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci. 2012 May/June;20(3):295-309.
5) Nailor MD, Sobel JD. Antibiotics for Gram-Positive Bacterial Infection: Vancomycin, Teicoplanin, Quinupristin/Dalfopristin, Oxazolidinones, Daptomycin, Telavancin, and Ceftaroline. Medical Clinics of North America. 2011 July;95(4):723-742.
6) Ford M. Medical Microbiology. New York: Oxford University Press; 2010.
7) Peppler M. Immunological Memory & Vaccines [unpublished lecture notes]. MLSCI 242: Clinical Microbiology, University of Alberta; lecture given 2012 Sep 28.
8) Madan R, Petri WA. Immune responses to Clostridium difficile infection. Trends Mol Med [serial on the Internet]. 2012 Nov [cited 2013 Feb 21]; 18(11): 658-66. Available from: PubMed.
9) Aboudola S, Kotloff KL, Kyne L, Warny M, Kelly EC, Sougioultzis S, et al. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun [serial on the Internet]. 2003 Mar [cited 2013 Feb 21]; 71(3): 1608-10. Available from: PubMed.
10) Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. The Lancet [serial on the Internet]. 2001 Jan 20 [cited 2013 Feb 21]; 357: 189-93. Available from: PubMed.
11) Peppler M. Microbe Cards. Canada: ASM Press; 2003.
12) Vaishnavi C. Clinical spectrum and pathogenesis of Clostridium difficile associated diseases. Indian J Res Med [serial on the Internet]. 2010 Apr [cited 2013 Mar 22]; 131:487-99. Available from: PubMed
13) Shen A. Clostridium difficile toxins: mediators of inflammation. J Innate Immun [serial on the Internet]. 2012 Feb [cited 2013 Mar 22]; 4(2): 149-158. Available from: PubMed
14) Boice JL. Reactive arthritis induced by Clostridium difficile. West J Med [serial on the Internet]. 1994 Feb [cited 2013 Mar 22]; 160(2): 171-2. Available from; PubMed
15) Voth DE, Ballard JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev [serial on the Internet]. 2005 Apr [cited 2013 Mar 22]; 18(2): 247-263. Available from: PubMed
16) Incidence of and risk factors for community-associated Clostridium difficile infection: A nested case-control study. BMC Infectious Diseases [serial on the Internet]. (2011, Jan), [cited March 24, 2013]; 11(1): 194-200. Available from: Academic Search Complete.
17) Jennifer R. O, Stuart J, Dale N. G. Clostridium difficile Infection Caused by the Epidemic BI/NAP1/027 Strain. Gastroenterology [serial on the Internet]. (n.d.), [cited April 5, 2013]; 136(Intestinal Microbes in Health and Disease): 1913-1924. Available from: ScienceDirect.
18) CDC’s Frequently Asked Questions about Clostridium difficile for Healthcare Providers [Internet]. Atlanta, USA: Centers for Disease Control and Prevention; 2010 [updated 2012 Mar 6; cited 2013 Apr 6]. Available from: http://www.cdc.gov/hai/organisms/cdiff/cdiff_faqs_hcp.html
Reactive Arthritis
Mechanism
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388264/
Toxins
Small Bowel
Effects
http://cmr.asm.org/content/18/2/247/F1.expansion.html
http://radiographics.rsna.org/content/20/2/399/F39.expansion.html
http://www.nature.com/nrmicro/journal/v9/n7/full/nrmicro2592.html
http://cmr.asm.org/content/18/2/247.long
http://bitchspot.jadedragononline.com/wp-content/uploads/2012/07/double-edged-sword.jpg
Innate Immunity
Humoral Immunity
Single vs. Recurrent
CDAD
http://www.biospectrumasia.com/IMG/562/9562/antibody-r-d-alliances-is-the-way-forward-262x174.jpg
Practical Applications
Environmental removal
Single-use disposable equipment :
Barrier nursing
Contact precautions :
http://www.fitsugar.com/How-Wash-Hands-Prevent-Colds-27889115
Antibiotic stewardship
http://www.guvestindia.com/oral-rectal-underarm-thermometer.htm
Non-disposable medical equipment :
Antibiotics
Cohorting :
Incidence
Fecal microbiota transplant
http://www.cleanlink.com/productwatch/details/Activate-Bleach-Dilution-System--4074
Disinfection of environmental surfaces :
These isolation precaution measures serve to minimize further spread of infection to staff or other patients.
Vaccines
http://nwitimes.com/app/gethealthy/?p=8385
Hypervirulent strains
Surgery
An initial infection of C. diff can produce an antibody response to Toxin A, leading to reduced recurrence and lasting immunity to some degree.
This immune response is the basis for developing immunizations against C. diff to prevent its onset and recurrence.
Risk factors
C. difficile incidence figures for England and Wales. Figures from The Health Protection Agency.
Stephen T. C, John T. H, Sarah A. K, Alan C, Nigel P. M. Mini Review: The emergence of ‘hypervirulence’ in Clostridium difficile. International Journal Of Medical Microbiology [serial on the Internet]. (n.d.), [cited April 5, 2013]; 300(Nosocomial Infections): 387-395.
http://healthwise-everythinghealth.blogspot.ca/2013/02/fecal-microbiota-transplants.html
http://4.bp.blogspot.com/-_qUGWI2V4Oo/TcQkyy6G2LI
/AAAAAAAAAEo/NyGGvsFek3I/s1600/Vaccines-full.jpg
Metronidazole Vancomycin Fidaxomicin
Patients with mild-to-moderate CDI
Similar efficacy as vancomycin
More efficacious in preventing recurrence
Newer drug (2011)
But... cost is significantly higher than that of vancomycin
Limit antibiotics used :
Antibiotic use is the biggest risk factor for CDI.
Patients with severe & severe complicated CDI
Bactericidal activity via inhibition of bacterial cell wall synthesis
FMT usually reserved if antibiotics fail
Healthy donor stool transplanted to stomach, small intestine, or colon of patients with RCDI.
Requires metabolic activation by strict anaerobe microorganisms
active metabolites which inhibit nucleic acid synthesis
breaks in DNA strands of targeted microbe
http://2012.igem.org/wiki/index.php?title=Team:NTU-Taida/Project/Safety&oldid=295963
http://www.weatherimagery.com/blog/grey-market-and-the-internet/dollar-sign/
But... potential for transmission of infectious agents is a concern
http://www.rowett.ac.uk/edu_web/DNA2.html
http://www.biologie.uni-hamburg.de/b-online/library/micro229/terry/229sp00/lectures/cells2.html
http://www.hse.gov.uk/workplacetransport/safetysigns/warning.htm
http://www.nlm.nih.gov/medlineplus/antibiotics.html
http://www.clearclinic.com/wp-content/uploads/2013/03/antibiotics-for-acne-best-acne-treatment.jpg
Clostridium difficile Infection Caused by the Epidemic BI/NAP1/027 Strain.
Jennifer R. O, Stuart J, Dale N. G. Clostridium difficile Infection Caused by the Epidemic BI/NAP1/027 Strain. Gastroenterology [serial on the Internet]. (n.d.), [cited April 5, 2013]; 136(Intestinal Microbes in Health and Disease): 1913-1924.
Toxoid vaccine DNA vaccine
Salvage therapy
Involves identifying factors controlling tissue invasion by C. difficile
Several vaccines are in trials
Surgery considered for the following CDI patients:
Safe and immunogenic in healthy volunteers
Synthetic gene encoding the receptor-binding domain of C. difficile toxin A has been produced and optimized for expression in human cells.
Future development: Multicomponent vaccines that prevent colonization and neutralize toxin activity = synergistic protection!!!
Loop ileostomy + intraoperative colon lavage + post-operative colonic vancomycin flushes
Sanofi Pasteur’s formalin-inactivated, highly purified preparation of toxoids A and B
Why? Reduce # of asymptomatic carriers by immunizing against colonization
http://www.colorectal-surgeon.com/stomas.htm
http://www.chiroone.net/commonConditions/crohns.html
colon preservation in >90% of patients + improved survival compared to historical colectomy patients
http://www.influenza.org.nz/?t=919
Rapid tests
Culture tests
Sample considerations
http://www.immunochemistry.com/products/elisa-solutions-for-immunoassay-development-in-vitro-diagnostic-assay-manufacturing.html
ONLY test patients with active diarrhea (we don't treat or isolate carriers)
For toxin EIA: toxins degrade after 2 hours at room temperature which can cause false negatives
http://depts.washington.edu/molmicdx/mdx/tests/cdiff.shtml
http://www.thestar.com/life/2012/12/13/cliff_the_beagle_can_detect_c_difficile_just_by_sniffing_air_around_infected_patients.html