Outline

Clostridium difficile

1Clostridium difficile: Clean DifferentlyInfection control measures to prevent transmission in inpatient settings

1C. difficile overviewPathogenesisBrief description of various testsTransmission of C. difficileIdentifying high-touch surfacesDaily cleaning vs. terminal cleaningProper use of bleachBrief intro to alternative cleaning products

2Outline2Historical Perspective Bacillus difficilis (now C. difficile) was cultured from healthy neonates in 1935In the 1960s it was noted that patients on antibiotics developed diarrheaStaphylococcal ColitisOriginally thought to be caused by S. aureus and treated with oral bacitracin Stool cultures routinely ordered for S. aureus Early 1970s, a new explanationClindamycin Colitis Severe diarrhea, pseudomembrane colitis, and occasional deaths documented in patients on clindamycin 3CDI 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

4C. 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).

5Prevalence

6Anaerobic, gram-positive, spore-forming, bacillusNon-toxin producing C. difficileToxin A (tcdA)Toxin B (tcdB)NAP1/BI/027 (deletion tcdC)Down regulation of toxin productionEnhance capability for production of toxin A and B.7Strains of C. difficile

Down regulation: a decrease in the number of receptors for a chemical or drug on cell surfaces in a given area, usually caused by long-term exposure to the agent

Definition: Development of a refractory or tolerant state consequent on repeated administration of a pharmacologically or physiologically active substance; often accompanied by an initial decrease in affinity of receptors for the agent and a subsequent diminution in the number of receptors.

78NAP1/BI/027 (deletion tcdC)

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Pathogenesis99Two forms of C. difficileVegetative

Spore10

11Crypts

12Normal vs. compromised

12

13Pathogenesis cont.

14Toxin effects on colon2 exotoxin that meadiate colitis and diarrheaToxin A causes inflammation leading to intestinal fluid secretion, mucosal injury and inflamation. Toxin A directly activates neutrophils and both toxin A and B can promote neautrophil chemotaxis to localize in pseudomembranes and underlying intestinal mucosal layer.

Toxin b is essential for the virulence of C. difficile , and is approximately 10 times more potent than toxin A for meadiating colonic mucosal damage.

Toxic C produces binary to14

15Pseudomembranes

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

Fever, cramping, abdominal discomfort, and peripheral leukocytosis but found only fewer than half of the patients (cohen, 2010)

16CultureCell cytotoxicity neutralization assayEnzyme immunoassays (EIA) C. difficiletoxin A (Tcd A)EIA TcdB or TcdA/BEIA, glutamate dehydrogenase (GDH)Nucleic acid amplification tests17Methods of testing C. difficile17Target: organismAdvantages:High sensitivity (often considered as the gold standard)Disadvantages:Turn-around time >7 daysLabor intensiveLacks specificityIsolates must be further tested for the presence of toxins

18CultureDoes not distinguish between toxigenic and non-toxigenic strains18Functional assay for C. difficile toxin B (TcdB)Advantages:Moderate-to-high sensitivityHigh specificityDisadvantages:48-72 hrs turn-around timeSubjective interpretationLabor intensive

19Cell cytotoxin neutrlization assayRequires skilled technicians/ technical expertise19Target: Toxin A detectionAdvantages:Easy to performRapid turn-around timeInexpensiveHigh specificityDisadvantages:Low sensitivityMissess TcdA-/TcdB+ isolates

20Enzyme immunoassays (EIA) C. difficiletoxin A (Tcd A)

20Target: Toxin A or B detectionAdvantages:Easy to performRapid turn-around timeInexpensiveHigh specificityDisadvantages:Low sensitivity

21EIA TcdB or TcdA/B

Method: common antigen detectionAdvantages:High sensitivityGood screening testDisadvantages:Low specificityMust test further22EIA, glutamate dehydrogenase (GDH)

Does not distinguish between toxigenic and non-toxigenic strainsMust be tested for toxins or toxin gene22Method: Toxin gene detectionAdvantages:High sensitivityHigh specificityShort-turn around timeEasy to perform, minimal hands onDisadvantages:ExpensiveDetection of asymptomatic colonization

23Nucleic acid amplification testsCost ten times more than the EIA test.

2324Combination method and algorithmReport as positiveReport as negativeNeed further testing2425Combination method and algorithmReport as negativeReport as positive2546 Consequences of Bad Tests Repeat testing Low sensitivity False negative patients dont get treated and spread the organism Low specificity False positive patients get costly treatments and IC protocols 26Practice change Send stool to lab right away or refrigerateIf GDH and EIA method are usedTest only symptomatic patient (3 loose stools in 24 hours)Test only loose stool (stick or conform)Test only one stool per patient per weekDo not test for cureAssess patient for other reasons for the diarrhea27Clinical 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 28Person 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 workerElectronic rectal thermometersInadequately cleaned commodes or bedpansTransmission of C. difficile

29Germs (skin bacteria)Culture plate showing growth of germs 24 hours after a nurse placed her hand on the plate

3030Before entering the room,Clean your hands with:ORSoap and WaterHand Sanitizer

31After Leaving the room:Wash with soap and water only

32Hand washing exercise32Acquisition of spores on gloved hands occurred as frequently after contact with environmental surfaces as after contact with skin sites (50% vs 50%)33Environmental source Electronic thermometers Blood pressure cuffs Bedside commodes Stethoscopes34Portable equipmentCohen SH, et al. ICHE 2010;31:31:431-55Omit confusing products35Confusing products

Focus on practices35House keeping ?Nurses?Central supply?Nobody?

36Confusion about who cleans what

Take Ownership

3637Sufficient contact time is necessary

Barbut F, et al. Infect Control Hosp Epidemiol 2009;30:507-14 37Stopping the spread: Cleaning and DisinfectionCleaning: Removal of organic matter and visible dirt

Disinfection: Killing of microorganisms3838Reducing contamination of cleaning solution and cleaning toolsLaundering 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, 200339Insist on microfiber3940High-touch surfaces

Huslage K, et al. A quantitative approach to defining high-touch surfaces in hospitals. Infect Control Hosp Epidemiol 2010;31:850-3. Provide the list of frequently touched surfaces4041Identify frequently touched surfaces

4142Monitor Cleaning

42Daily CleaningWipe all high-touch surface dailyTwo wipe system, Clean and DisinfectMinimizing mist and aerosol dispersion

43An elderly person in your household develops diarrhea that is diagnosed as an infectious viral illness. There are young children in the household who interact regularly with the ill person. Do you: Wait 10 days until the illness has completely resolved before cleaning the bathroom and other objects that the person contacts Disinfect surfaces daily or after each use of the bathroom to prevent transmission Regardless of patient status4344One bleach wipe multiple time vs. fresh one each time

44Terminal/ Dischrage CleaningClean 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 minutes454546Quat vs Bleach

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Diluted bleach only stable only for 24 hrs47Diluted bleach

47One- Step detergent disinfectantComponents:Peroxyacetic acid 0.05% Hydrogen peroxide 3.13% Octanoic acid 0.099%Kills C. difficile spores in 10 minutesEffective with 5% organic load (peracetic acid is not affected as much as bleech by organic load)Compatible with materials

48Peroxyacetic acid/ hydrogen peroxide/ Octanoic acid combinationViracept (EcoLab)Smells like strong vinegar

48Precautionary Statement:Danger: Causes irreversible eye damage. Do not get in eyes or on clothing. Wear goggles, face shield, or shielded safety glasses.49Peroxyacetic acid/ hydrogen peroxide/ Octanoic acid combination

50Hydrogen peroxide mist 2.5-3.5 hours of running time. Hydrogen peroxide Hydrogen peroxide aerosolized mist vapor (Bioquell) dry (ASP Glosair) % hydrogen peroxide 35% 5% Close vents/seal room Yes Yes Sporicidal efficacy >6 log reduction C. difficile ~4 log reduction C. difficile Cycle time 2 hours 20 minutes - 3 hours 3.5 hours Evidence of clinical impact Yes reduction in C. difficile and control of outbreaks None published

Hydrogen peroxide Hydrogen peroxide aerosolized mist vapor (Bioquell) dry (ASP Glosair) % hydrogen peroxide 35% 5% Close vents/seal room Yes Yes Sporicidal efficacy >6 log reduction C. difficile ~4 log reduction C. difficile Cycle time 2 hours 20 minutes - 3 hours 3.5 hours Evidence of clinical impact Yes reduction in C. difficile and control of outbreaks None published

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51UV light51Identify frequently touched surfacesList them and give copies to housekeeping personnelIdentify ownership of equipment cleaningUse EPA registered sporicidalClean then disinfect even with one-step productsImplement daily cleaning52Conclusion52

53QuestionsAssociation 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&sid=d69405ae-17ec-4e87-b3d7-2fe1cb0adbcb%40sessionmgr12Barbut, 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.0b013e32834748e5Clostridium difficile Excerpt: Guideline for Environmental Infection Control in Health-Care Facilities, 2003. (2003). www.cdc.gov/HAI/organisms/cdiff/Cdiff_excerpt.html

54ReferencesCohen, 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: 10.1086/651706Gould, C. V., & McDonald, C. (2008, January). Bench-to-bedside review: Clostridium difficile colitis. Critical Care. doi: 10.1186/cc6207Huslage 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.2011.1569LaMont, 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+Clostridium+difficile+infection&selectedTitle=1%7E150

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