1. 1

2.   C. difficile overview  Pathogenesis  Brief description of various tests  Transmission of C. difficile  Identifying high-touch surfaces  Daily cleaning vs. terminal cleaning  Proper use of bleach  Brief intro to alternative cleaning products 2 Outline

3. Historical Perspective  Bacillus difficilis (now C. difficile) was cultured from healthy neonates in 1935  In the 1960’s it was noted that patients on antibiotics developed diarrhea  “Staphylococcal Colitis”  Originally thought to be caused by S. aureus and treated with oral bacitracin  Stool cultures routinely ordered for S. aureus  Early 1970’s, a new explanation  “Clindamycin Colitis”  Severe diarrhea, pseudomembrane colitis, and occasional deaths documented in patients on clindamycin

4. CDI Overview  Spore-forming, anaerobic, gram-positive bacterium  Causes gastrointestinal infections resulting in diarrhea and colitis  – Severity ranges from mild colitis to toxic megacolon and death  Leading cause of healthcare-associated infectious diarrhea in US  Rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common organism to cause healthcare-associated infections in US

5.   C. difficile causes about 500,000 illnesses in the United States every year (Kuchn, 2011).  In the United States, estimated 15000-20000 patients die from the illness each year (Barbut, Jones, & Eckert, 2011).  In the general population, one to three percent of adults are colonized with the organism (Barbut et al., 2011). However, about 20 percent of hospitalized adults are C. difficile carriers (LaMont, 2009). 5 Prevalence

6.  6

7.   Anaerobic, gram-positive, spore-forming, bacillus  Non-toxin producing C. difficile  Toxin A (tcdA)  Toxin B (tcdB)  NAP1/BI/027 (deletion tcdC)  Down regulation of toxin production  Enhance capability for production of toxin A and B. 7 Strains of C. difficile

8.  8 NAP1/BI/027 (deletion tcdC)

9.  Pathogenesis 9

10.  Two forms of C. difficile VegetativeSpore 10

11.  11 Crypts

12.  12 Normal vs. compromised

13.  13 Pathogenesis cont.

14.  14 Toxin effects on colon

15.  15 Pseudomembranes

16.   Watery diarrhea is the cardinal clinical symptoms  Diarrhea can be up to 15 times per day  Fever, cramping, abdominal discomfort, and peripheral leukocytosis (cohen, 2010)  Colonic ileus or toxic dilatation may present with no or minimal diarrhea. 16 Clinical Symptoms

17.   Culture  Cell cytotoxicity neutralization assay  Enzyme immunoassays (EIA) C. difficile toxin A (Tcd A)  EIA TcdB or TcdA/B  EIA, glutamate dehydrogenase (GDH)  Nucleic acid amplification tests 17 Methods of testing C. difficile

18.   Target: organism  Advantages:  High sensitivity (often considered as the gold standard)  Disadvantages:  Turn-around time >7 days  Labor intensive  Lacks specificity  Isolates must be further tested for the presence of toxins 18 Culture

19.   Functional assay for C. difficile toxin B (TcdB)  Advantages:  Moderate-to-high sensitivity  High specificity  Disadvantages:  48-72 hrs turn-around time  Subjective interpretation  Labor intensive 19 Cell cytotoxin neutrlization assay

20.   Target: Toxin A detection  Advantages:  Easy to perform  Rapid turn-around time  Inexpensive  High specificity  Disadvantages:  Low sensitivity  Missess TcdA-/TcdB+ isolates 20 Enzyme immunoassays (EIA) C. difficile toxin A (Tcd A)

21.   Target: Toxin A or B detection  Advantages:  Easy to perform  Rapid turn-around time  Inexpensive  High specificity  Disadvantages:  Low sensitivity 21 EIA TcdB or TcdA/B

22.   Method: common antigen detection  Advantages:  High sensitivity  Good screening test  Disadvantages:  Low specificity  Must test further 22 EIA, glutamate dehydrogenase (GDH)

23.   Method: Toxin gene detection  Advantages:  High sensitivity  High specificity  Short-turn around time  Easy to perform, minimal hands on  Disadvantages:  Expensive  Detection of asymptomatic colonization 23 Nucleic acid amplification tests

24.  GDH Negative Toxin(s) negative Enzyme immunoassay (EIA) GDH and Toxin(s) GDH positive Toxin(s) positive Enzyme immunoassay (EIA) GDH and Toxin(s) GDH positive Toxin(s) negative Enzyme immunoassay (EIA) GDH and Toxin(s 24 Combination method and algorithm Report as positive Report as negative Need further testing

25.  Nucleic acid amplification tests positivenegative Enzyme immunoassay (EIA) GDH and Toxin(s) GDH positiveToxin negative 25 Combination method and algorithm Report as negative Report as positive

26. 46 Consequences of Bad Tests  Repeat testing  Low sensitivity  – False negative patients don’t get treated and spread the organism  Low specificity  – False positive patients get costly treatments and IC protocols

27. Practice change  Send stool to lab right away or refrigerate If GDH and EIA method are used  Test only symptomatic patient (3 loose stools in 24 hours)  Test only loose stool (stick or conform)  Test only one stool per patient per week  Do not test for cure  Assess patient for other reasons for the diarrhea

28. Clinical Practice Guidelines 2010 SHEA and IDSA Summary  Test only unformed stool (exception: ileus)  Do not perform a test of cure  Stool cultures sensitive but not practical except for epidemiological studies  EIA is rapid, not very sensitive and is sub-optimal  2 step GDH and EIA is a interim recommendation  More data needed on PCR before they can recommend  Repeat testing discouraged Cohen, S.H. et al. 2010. ICHE. 31: 431-455

29.   Person to person by swallowing fecal matter.  Periods between exposure C. difficile and the occurrences 2- 3 days (cohen, 2010)  Culprits in healthcare:  Contaminated hands of healthcare worker  Electronic rectal thermometers  Inadequately cleaned commodes or bedpans Transmission of C. difficile 29

30.  Germs (skin bacteria) Culture plate showing growth of germs 24 hours after a nurse placed her hand on the plate 30

31.  Before entering the room, Clean your hands with: OR Soap and WaterHand Sanitizer 31

32.  After Leaving the room: Wash with soap and water only 32

33.   Acquisition of spores on gloved hands occurred as frequently after contact with environmental surfaces as after contact with skin sites (50% vs 50%) 33 Environmental source

34.   Electronic thermometers  Blood pressure cuffs  Bedside commodes  Stethoscopes 34 Portable equipment Cohen SH, et al. ICHE 2010;31:31:431-55

35.   Omit confusing products 35 Confusing products

36.   House keeping ?  Nurses?  Central supply?  Nobody? 36 Confusion about who cleans what

37.  37 Sufficient contact time is necessary Barbut F, et al. Infect Control Hosp Epidemiol 2009;30:507-14

38.  Stopping the spread: Cleaning and Disinfection Cleaning: Removal of organic matter and visible dirt Disinfection: Killing of microorganisms 38

39.  Reducing contamination of cleaning solution and cleaning tools  Laundering microfiber/swiffer after each room cleaning.  Replace soiled microfiber/swiffer with clean item each time a bucket or detergent/disinfectant is emptied or replaced.  Keeping microfibers/swiffers in solutions do not kill all the bugs, some bugs can grow in the solution.  Make sufficient cleaning solution for the day, emptying the solution and drying out the container minimize contamination. Clostridium difficile Excerpt: Guideline for Environmental Infection Control in Health-Care Facilities, 2003 39

40.  40 High-touch surfaces Huslage K, et al. A quantitative approach to defining high-touch surfaces in hospitals. Infect Control Hosp Epidemiol 2010;31:850-3.

41.  41 Identify frequently touched surfaces

42.  42 Monitor Cleaning

43.  Daily Cleaning  Wipe all high-touch surface daily  Two wipe system, Clean and Disinfect  Minimizing mist and aerosol dispersion 43

44.  44 One bleach wipe multiple time vs. fresh one each time

45.  Terminal/ Dischrage Cleaning  Clean all high-touch surfaces and all other area including wall with quaternary solution  Then disinfect with bleach wipe or bleach solution.  Stay wet for 10 minutes 45

46.  46 Quat vs Bleach

47.   Diluted bleach only stable only for 24 hrs 47 Diluted bleach

48.   One- Step detergent disinfectant  Components:  Peroxyacetic acid 0.05%  Hydrogen peroxide 3.13%  Octanoic acid 0.099%  Kills C. difficile spores in 10 minutes  Effective with 5% organic load (peracetic acid is not affected as much as bleech by organic load)  Compatible with materials 48 Peroxyacetic acid/ hydrogen peroxide/ Octanoic acid combination

49.   Precautionary Statement:  Danger: Causes irreversible eye damage. Do not get in eyes or on clothing. Wear goggles, face shield, or shielded safety glasses. 49 Peroxyacetic acid/ hydrogen peroxide/ Octanoic acid combination

50.  50 Hydrogen peroxide mist

51.  51 UV light

52.   Identify frequently touched surfaces  List them and give copies to housekeeping personnel  Identify ownership of equipment cleaning  Use EPA registered sporicidal  Clean then disinfect even with one-step products  Implement daily cleaning 52 Conclusion

53.  53 Questions

54.   Association for Professionals in Infection Control and Epidemiology. (2008). Guide to the Elimination of Clostridium difficile in Healthcare Settings Washington, DC: APIC.  Banning, M. (2008, December). Understanding the microbiology, prevalence and pathology of Clostridium difficile. Gastrointestinal Nursing, 6 (10). Retrieved from http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=4&hid=25&s id=d69405ae-17ec-4e87-b3d7-2fe1cb0adbcb%40sessionmgr12  Barbut, F., Jones, G., & Eckert, C. (2011). Epidemiology and control of Clostridium difficile infections in healthcare settings: an update. Nosocomial and health-related infections. doi: 10.1097/qco.0b013e32834748e5  Clostridium difficile Excerpt: Guideline for Environmental Infection Control in Health-Care Facilities, 2003. (2003). www.cdc.gov/HAI/organisms/cdiff/Cdiff_excerpt.html 54 References

55.   Cohen, S. H., Gerding, D. N., Johnson, S., Kelly, C. P., Loo, V. G., McDonald, C.,... Wilcox, M. H. (2010, March 22). Clinical practice guidelines for Clostridium difficle infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology, 31 (5). doi: 10.1086/651706  Gould, C. V., & McDonald, C. (2008, January). Bench-to-bedside review: Clostridium difficile colitis. Critical Care. doi: 10.1186/cc6207  Huslage K, et al. A quantitative approach to defining high-touch surfaces in hospitals. Infect Control Hosp Epidemiol 2010;31:850-3.  Kuchn, B. (2011). Scientists seek strategies to prevent Clostridium difficile infections. JAMA, 306 (17), 1849-1850. doi: 10.1001/jama.2011.1569  LaMont, J. (2012, June 11). Clinical manifestations and diagnosis of Clostridium difficile infection. UpToDate. Retrieved fromhttp://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of- clostridium-difficile-infection-in- adults?source=search_result&search=Clinical+manifestations+and+diagnosis+of+Cl ostridium+difficile+infection&selectedTitle=1%7E150http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of- clostridium-difficile-infection-in- adults?source=search_result&search=Clinical+manifestations+and+diagnosis+of+Cl ostridium+difficile+infection&selectedTitle=1%7E150 55 References