1. Prevention of Clostridium difficile Infection (CDI) Massachusetts CDI Prevention Collaborative Carolyn Gould, MD MSCR L. Cliff McDonald, MD Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Disclaimer: The findings and conclusions in this presentation are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

2. Objectives Describe the impact and changing epidemiology of C. difficile infection (CDI) Discuss the pathogenesis of CDI Review HHS Prevention Targets Discuss Core and Supplemental Strategies for Prevention of CDI – Contact Precautions – Hand hygiene – Environmental cleaning – Diagnostic testing – Antimicrobial stewardship

3. Background: Impact Hospital-onset: 165,000 cases, $1.3 billion in excess costs, and 9,000 deaths annually Community-onset, healthcare-facility associated: 50,000 cases, $0.3 billion in excess costs, and 3,000 deaths annually Nursing home-onset: 263,000 cases, $2.2 billion in excess costs, and 16,500 deaths annually Campbell et al. Infect Control Hosp Epidemiol. 2009:30:523-33 Dubberke et al. Emerg Infect Dis. 2008;14:1031-8 Dubberke et al. Clin Infect Dis. 2008;46:497-504 Elixhauser et al. HCUP Statistical Brief #50. 2008

4. Heron et al. Natl Vital Stat Rep 2009;57(14). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf Age-Adjusted Death Rate* for Enterocolitis Due to C. difficile, 1999– 2006 *Per 100,000 US standard population 0 0.5 1.0 1.5 2.0 2.5 19992003 Rate 200020042001200520022006 Year Male Female White Black Entire US population

5. Mortality due to C. difficile Infection per 100,000 population, Massachusetts http://wonder.cdc.gov/mortSQL.html

6. Background: Epidemiology Current epidemic strain of C. difficile BI/NAP1/027, toxinotype III Historically uncommon – epidemic since 2000 More resistant to fluoroquinolones Higher MICs compared to historic strains and current non- BI/NAP1 strains More virulent Increased toxin A and B production Polymorphisms in binding domain of toxin B Increased sporulation McDonald et al. N Engl J Med. 2005;353:2433-41 Warny et al. Lancet. 2005;366:1079-84 Stabler et al. J Med Micro. 2008;57:771–5 Akerlund et al. J Clin Microbiol. 2008;46:1530–3

7. Sunenshine et al. Cleve Clin J Med. 2006;73:187-97 Pathogenesis of CDI 4. Toxin A & B Production leads to colon damage +/- pseudomembrane 1. Ingestion of spores transmitted from other patients via the hands of healthcare personnel and environment 2. Germination into growing (vegetative) form 3. Altered lower intestine flora (due to antimicrobial use) allows proliferation of C. difficile in colon

8. Background: Epidemiology Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds ? Gastric acid suppression Main modifiable risk factors

9. HHS Prevention Targets http://www.hhs.gov/ophs/initiatives/hai/appendices.html Metric Original HAI Elimination Metric HAI Comparison Metric Measurement System National Baseline Established National 5- Year Prevention Target Coordinator of Measurement System Is the Metric NQF Endorsed? C diff 1Case rate per patient days; administrativ e/ discharge data for ICD- 9 CM coded C. difficile Infections Hospitalizatio ns with C. difficile per 1,000 patient discharges Hospital discharge data 2008At least 30% reduction in hospitalization s with C. difficile per 1,000 patient discharges AHRQ or CDCNo C diff 2 C. difficile SIRCDC NHSN MDRO/CDAD Module LabID‡ 2009-2010Reduce the facility-wide healthcare facility-onset C. difficile LabID event SIR by at least 30% from baseline CDCNo

10. Prevention Strategies Core Strategies – High levels of scientific evidence – Demonstrated feasibility Supplemental Strategies – Some scientific evidence – Variable levels of feasibility *The Collaborative should at a minimum include core prevention strategies. Supplemental prevention strategies also may be used. Most core and supplemental strategies are based on HICPAC guidelines. Strategies that are not included in HICPAC guidelines will be noted by an asterisk (*) after the strategy. HICPAC guidelines may be found at www.cdc.gov/hicpac

11. Core Prevention Strategies Contact Precautions for duration of diarrhea Hand hygiene in compliance with CDC/WHO Cleaning and disinfection of equipment and environment Laboratory-based alert system for immediate notification of positive test results Educate about CDI: HCP, housekeeping, administration, patients, families www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92

12. Supplemental Prevention Strategies Extend use of Contact Precautions beyond duration of diarrhea (e.g., 48 hours)* Presumptive isolation for symptomatic patients pending confirmation of CDI Evaluate and optimize testing for CDI Implement soap and water for hand hygiene before exiting room of a patient with CDI Implement universal glove use on units with high CDI rates* Use sodium hypochlorite (bleach) – containing agents for environmental cleaning Implement an antimicrobial stewardship program * Not included in CDC/HICPAC 2007 Guideline for Isolation Precautions

13. Contact Precautions Gloves/gowns on room entry Private room (preferred) or cohort with dedicated commodes Dedicated equipment Maintain for duration of diarrhea Measure compliance Extend use of Contact Precautions beyond duration of diarrhea Presumptive isolation Universal glove use on units with high CDI rates Intensify assessment of compliance www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31 CoreSupplemental

14. Rationale for considering extending isolation beyond duration of diarrhea Bobulsky et al. Clin Infect Dis 2008;46:447-50

15. Patients should meet criteria for testing and presumptive isolation >3 unformed (i.e., taking the shape of a container) stools within 24 hours – Send specimen for testing and presumptively isolate patient pending results – Positive predictive value of testing optimized if focused on patients with >3 unformed stools within 24 hours – Exception: patient with possible recurrent CDI (isolate and test following first unformed stool)

16. Rationale for considering universal glove use on units with high CDI rates Asymptomatic carriers may have a role in transmission (magnitude uncertain) Practical screening tests not available Still require Contact Precautions for patients with known CDI Focus enhanced environmental cleaning strategies and avoid shared medical equipment on such units as well

17. Riggs et al. Clin Infect Dis 2007;45:992–8 Role of asymptomatic carriers?

18. http://www.cdc.gov/nhsn/forms/57.127_MDROMonthlyReporting_BLANK.pdf

19. Hand Hygiene Hand hygiene based on CDC or WHO guidelines Soap and water preferentially in outbreak or hyperendemic settings Measure compliance Soap and water for hand hygiene before exiting room of a patient with CDI Intensify assessment of compliance www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31 CoreSupplemental

20. Hand Hygiene – Soap vs. Alcohol gel Alcohol not effective in eradicating C. difficile spores But in clinical practice, is soap and water better? – Effect on HH adherence and transmission of other HAIs unclear Increased adherence with alcohol hand rub Limited availability of sinks in many facilities – Recent data suggesting spore adherence to skin and difficulty removing spores with soap and water – Incremental benefit of soap and water vs. alcohol with glove use? Ellingson K, McDonald C. Infect Control Hosp Epidemiol 2010;31:571-3

21. Boyce et al. Infect Control Hosp Epidemiol 2006;27:479-83

22. Hand Washing: Product Comparison ProductLog10 Reduction Tap Water0.76 4% CHG antimicrobial hand wash0.77 Non-antimicrobial hand wash0.78 Non-antimicrobial body wash0.86 0.3% triclosan antimicrobial hand wash0.99 Heavy duty hand cleaner used in manufacturing environments 1.21* * Only value that was statistically better than others Edmonds, et al. Presented at: SHEA 2009; Abstract 43 Johnson et al. Am J Med 1990;88:137-40 Conclusion: Spores may be difficult to eradicate even with hand washing Emphasizes need for absolute adherence with glove use

23. Environmental Cleaning Cleaning and disinfection of equipment and environment Consider sodium hypochlorite in outbreak or hyperendemic settings Routinely assess adherence to protocols and adequacy of cleaning Reassess adequacy of room cleaning and address issues Use sodium hypochlorite (bleach) – containing agents www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31 CoreSupplemental

24. Environmental Cleaning Bleach can kill spores, whereas other standard disinfectants cannot Limited data suggest cleaning with bleach (1:10 dilution prepared fresh daily) reduces C. difficile transmission Two before-after intervention studies demonstrated benefit of bleach cleaning in units with high endemic CDI rates Therefore, bleach may be most effective in reducing burden where CDI is highly endemic Mayfield et al. Clin Infect Dis 2000;31:995-1000 Wilcox et al. J Hosp Infect 2003;54:109-14

25. Environmental Cleaning Assess adequacy of cleaning before changing to new cleaning product such as bleach Ensure that environmental cleaning is adequate and high-touch surfaces are not being overlooked A fluorescent environmental marker is one method to asses cleaning and can lead to sustained improvement in cleaning following education The use of environmental markers is a promising method to improve cleaning in hospitals Carling et al. Clin Infect Dis 2006;42:385-8

26. Diagnostic Testing Laboratory-based alert system for immediate notification of positive test results Evaluate and optimize testing for CDI www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31 CoreSupplemental

27. Evaluate and optimize test-ordering practices and diagnostic methods Toxin A/B enzyme immunoassays have low sensitivities (70-80%) Despite high specificity, poor test ordering practices (i.e. testing formed stool or repeat testing) may lead to false positives Consider more sensitive diagnostic paradigms but apply these more judiciously – Employ a highly sensitive screen with confirmatory test or a PCR-based molecular assay – Restrict testing to unformed stool only – Focus testing on patients with > 3 unformed stools within 24 hours – Require expert consultation for repeat testing within 5 days Peterson et al. Ann Intern Med 2009;15:176-9.

28. Antimicrobial Stewardship Along with transmission, main modifiable risk factor for CDI 40-50% of antibiotic use may be unnecessary Clinical Infectious Diseases 2007; 44:159–77

29. Audit and feedback targeting broad-spectrum antibiotics A prospective, controlled interrupted time-series analysis in 3 acute medical wards for the elderly Introduced a narrow- spectrum antibiotic policy Reinforced using feedback Reductions in targeted antibiotics and CDI Fowler et al. J Antimicrob Chemother 2007;59:990-5

31. Desperate Measures for Desperate Times: Restricting all Fluoroquinolones to End an Outbreak Kallen, et al. 18th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 6, 2008; Orlando, FL. Number of Cases Month and Year Beginning of outbreak period Quinolone restriction New housekeeping company Quinolone restriction partially lifted 2004 2005 2006 2007

32. 20052006 2007 Month and year Pre-intervention 6.6% increase/month (p<0.001) Immediate effect of FQ restriction 28% drop (p=0.15) Post-intervention (P<0.006) Time Series Model HO-CDAD cases/1,000 pd Proportion of isolates that were epidemic strain decreased 66% (43) before interventions to 44% (25) after (p=0.02)

33. Quinolone Restriction Period Nimber of Defined Daily Doses 2005 20062007 Month and Year Impact that Restricting Fluoroquinolones can Have on Reducing Unnecessary Antimicrobial Use 0 500 1000 1500 2000 2500 JunJulAugSepOctNovDecJanFebMarAprMayJunJulAugSepOctNovDecJanFebMar AminoglycosidesCephalosporins (1st gen.) Cephalosporins (2nd gen.)Cephalosporins (3rd and 4th gen.) QuinolonesVancomycin Piperacillin/TazobactamAmpicillin/Sulbactam AzithromycinCarbapenems AztreonamClindamycin Kallen, et al. 18th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 6, 2008; Orlando, FL.

34. Antibiotic Stewardship Drivers and Change Package Partnership between CDC and IHI Develop a conceptual model of key drivers for reducing inappropriate antibiotic utilization Goal: set of recommendations for all hospitals regardless of size, acuity, setting – Implementation tailored to needs and resources of facility – Prototyping in pilot hospitals

35. Measurement: Outcome Categorize Cases by location and time of onset † AdmissionDischarge < 4 weeks 4-12 weeks HOCO-HCFAIndeterminateCA-CDI Time 2 d > 12 weeks * HO: Hospital (Healthcare)-Onset CO-HCFA: Community-Onset, Healthcare Facility-Associated CA: Community-Associated * Depending upon whether patient was discharged within previous 4 weeks, CO-HCFA vs. CA † Onset defined in NHSN LabID Event by specimen collection date Modified from CDAD Surveillance Working Group. Infect Control Hosp Epidemiol 2007;28:140-5 Day 1Day 4

36. Measurement: Outcome NHSN CDAD Module

37. http://www.cdc.gov/HAI/recoveryact/stateResources/stateResources.html

38. Evaluation Considerations Assess baseline policies and procedures Areas to consider – Surveillance – Prevention strategies – Measurement of effect of strategies Coordinator should track new policies/practices implemented during collaboration Standardized questions available at: http://www.cdc.gov/HAI/recoveryact/stateResources/stateResources.html

39. http://www.cdc.gov/HAI/recoveryact/PDF/CDI_EvalQuestions_Final_Clearedversion32910.pdf

40. Additional resources Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 CDI Checklist Example Abbett SK et al. Infect Control Hosp Epidemiol 2009;30:1062-9 Cohen et al. Infect Control Hosp Epidemiol 2010;31

41. Example of Success: UK Experience http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1274091661838

42. Objectives Describe the impact and changing epidemiology of C. difficile infection (CDI) Discuss the pathogenesis of CDI Review HHS Prevention Targets Discuss Core and Supplemental Strategies for Prevention of CDI – Contact Precautions – Hand hygiene – Environmental cleaning – Diagnostic testing – Antimicrobial stewardship

43. Thank you! Questions? CGould@cdc.gov