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Clostridium difficile : An overview

Clostridium difficile : An overview. CDI Webinar July 11, 2017. Outline. Background Microbiology Burden Pathogenesis Diagnostic testing Treatment Prevention Antimicrobial stewardship Practical approach to CDI prevention How is your facility dealing with CDI?.

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Clostridium difficile : An overview

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  1. Clostridium difficile: An overview CDI Webinar July 11, 2017 PUBLIC HEALTH DIVISIONAcute and Communicable Disease Prevention Section

  2. Outline • Background • Microbiology • Burden • Pathogenesis • Diagnostic testing • Treatment • Prevention • Antimicrobial stewardship • Practical approach to CDI prevention • How is your facility dealing with CDI?

  3. Background: Microbiology, Burden, Pathogenesis

  4. C. difficile: Microbiology • Gram-positive spore-forming obligate anaerobic rod-shaped bacterium • 1935: part of flora of healthy infants; Bacillus difficilis • 1-3% of heatlhy adults • 70% of children < 12 months • 1970s: C. difficile CDAD (CDI preferred) • Toxins-producing strains cause C. difficile infection (CDI) Smits Nat Rev Dis Primers. 2016 Apr 7; 2:16020. doi: 10.1038/nrdp.2016.20

  5. Time line for surveillance definitions of CDI Admission Discharge < 4 weeks 4-12 weeks > 12 weeks 2 d HO CO-HCFA Indeterminate CA-CDI * Day 1 Day 4 Time HO: Hospital (Healthcare)-Onset CO-HCFA: Community-Onset , Healthcare Facility-Associated CA: Community-Associated * Depending upon whether patient was discharged within previous 12 weeks Onset defined in NHSN by specimen collection date

  6. C. difficile: Impact • 453,000 CDI cases1 • 293,000 healthcare-associated • 107,000 hospital-onset • 104,000 nursing home-onset • 81,000 community-onset, healthcare-facility associated • 160,000 community-associated • 82% associated with outpatient healthcare exposure Overall, 94% of CDI cases related to healthcare • 29,000 deaths • $4.8 billion in excess healthcare costs2 Estimated U.S. Burden of CDI, According to the Location of Stool Collection and Inpatient Health Care Exposure, 2011. CO-HCA: Community onset healthcare-associated NHO: Nursing home onset HO: Hospital onset Lessa et al. N Engl J Med 2015; 372(9):825-834. Dubberke et al. Clin Infect Dis 2012; 55:S88-92.

  7. C. difficile: Impact • C. difficile most commonly reported pathogen in 2011 multistate prevalence survey of healthcare-associated infections (HAI)1 • 12.1% of 452 HAIs caused by CDI • Rates of CDI per 1,000 discharges have risen through 20132 Magill et al. N Engl J Med 2014; 370:1198-1208. Steiner et al. HCUP Projections Report 2014-01.

  8. Oregon C. difficile standardized infection ratios (SIR): 2012-2015

  9. C. difficile : Transmission • Fecal-oral route • Contaminated hands of healthcare workers • Contaminated environmental surfaces. • Reservoir • Human:colonized or infected persons • Contaminated environment • C. difficile spores can survive for up to 5 months on environmental surfaces.

  10. CDI: Pathogenesis Step 1- Ingestion of spores transmitted from reservoirs Step 2- Germination into growing (vegetative) form Step 4 - Toxin B & A production leads to colon damage +/- pseudomembrane Step 3 - Altered lower intestine flora (due to antimicrobial use) allows proliferation of C. difficile in colon

  11. CDI Pathogenesis Colonized no symptoms Antimicrobials C Diff exposure & acquisition Admitted to healthcare facility Infected Symptomatic

  12. CDI: Host risk factors

  13. CDI: Modifiable risk factors

  14. Clinical manifestations • Illness caused by toxin-producing strains of C. difficile ranges from • Asymptomatic carriers = Colonized • Mild or moderate diarrhea • Pseudo membranous colitis that can be fatal • A median time between exposure to onset of CDI symptoms is of 2–3 days • Risk of developing CDI after exposure ranges between 5-10 days to 10 weeks

  15. CDI: Symptoms Watery diarrhea ( > 3 unformed stools in 24 or fewer consecutive hours) Loss of appetite Fever Nausea Abdominal pain and cramping

  16. Epidemiology: Epidemic Strain • BI/NAP1/027, toxinotype III • First emerged in 2000 (Eastern Canada)1 • Associated with healthcare2 • More resistant to fluoroquinolones3 • Greater virulence • Associated with more severe disease and mortality4 • Increased toxin A and B production4,5 • Polymorphisms in binding domain of toxin B5 • Oregon: 16% (11 of 68) strains with PFGE performed

  17. Diagnostic testing

  18. Best Strategy for C. difficile Testing 2. Dubberke et al. Infect Control HospEpidemiol 2014; 35 (6):628-645 Testing should be performed only on diarrheal stool Testing asymptomatic patients is not indicated Testing for cure is not recommended

  19. Diagnostic tests for toxigenic C. difficile References

  20. Diagnostic tests for toxigenic C. difficile References

  21. Guidance from the American Society for Microbiology 1. Am Soc Microbiol, 2010. Toxin A/B enzyme immunoassays have low sensitivity and should not be used as stand alone tests.1 Highly sensitive screening tests like glutamate dehydrogenase antigen assays (GDH) should have positive results confirmed. Nucleic acid amplification that detects C. difficile toxin genes may be used as a stand alone test.

  22. Sample multistep algorithm for rapid diagnosis of C. difficile infection JAMA. 2015;313(4):398-408. doi:10.1001/jama.2014.17103

  23. Studies examining performance characteristics of multistep algorithms for rapid diagnosis of C. difficile infection NAAT-containing algorithms perform better Bagdasarian JAMA. 2015;313(4)398-408. doi:10.1001/jama.2014.17103

  24. Treatment

  25. Treatment options for CDI Smits Nat Rev Dis Primers. 2016 Apr 7; 2:16020. doi: 10.1038/nrdp.2016.20

  26. Fecal microbiota transplant

  27. Prevention

  28. Overview • Basic practices are prevention measures that should be in place at all times. • Facilities should consider adopting some or all of the special approaches whenever ongoing opportunities for improvement are identified or as indicated by risk assessment. Dubberke et al. Infect Control Hosp Epidemiol 2014; 35(6):628-645.

  29. Antimicrobial Stewardship • Chang et al. Infect Control Hosp Epidemiol 2007; 28(8):926–931. • Hensgens et al. J Antimicrob Chemother 2012; 67(3):742-748. • Hsu et al. Am J Gastroenterol 2010; 105(11):2327–2339. Exposure to any antimicrobial is the single most important risk factor for C. difficile infection (CDI). • Antibiotic exposure has lasting impact on the microbiome. • Risk of CDI is elevated (7-10 fold) during and in the 3 months following antimicrobial therapy1,2 • 85-90% of CDI occurs within 30 days of antimicrobial exposure1 • Target high risk antibiotics for CDI prevention • Fluoroquinolones3 • 3rd/4th generation cephalosporins, carbapenems2

  30. Currently 39% (1,642/4,184) of U.S. hospitals have an antibiotic stewardship program with all 7 core elements. The national goal is 100% of hospitals by 2020. http://www.cdc.gov/getsmart/healthcare/evidence.html

  31. Seven Core Elements of Antimicrobial Stewardship http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html 1. Leadership Commitment Dedicating necessary human, financial, technological resources 2. Accountability Appointing a single leader (physician or pharmacist) responsible for program outcomes 3. Drug Expertise A single dedicated pharmacist with responsibility to improve antibiotic use 4. Tracking Monitoring antibiotic prescribing and resistance patterns 5. Reporting Feedback of information on antibiotic use and resistance to frontline providers 6. Education Ongoing education of clinicians about resistance and optimal prescribing 7. Action Implementing at least one recommended action

  32. Stewardship Approach: Feedback Reductions in CDI attained through antimicrobial stewardship surpassed those attained through infection control measures. Tertiary Hospital in Quebec, 2003-2006 Valiquette et al. Clin Infect Dis 2007; 45:S112-121. Non-restrictive feedback resulted in statistically significant reductions in incident CDI.

  33. Stewardship Approach: Restriction Restricting the use of ceftriaxone was associated with reduced rates of CDI. Formal restriction implemented District general hospital; Glasgow, UK, 2007-2009 Fig. 1 Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile and extended-spectrum β-lactamase (ESBL)-producing coliform rates following a restrictive antibiotic policy in a district general hospital over 2 years. pt/occ.bds, patient-occupied bed-days; DDDs, defined daily doses. Dancer et al. Intl J Antimicrob Agents 2013; 41(2):137-142.

  34. A practical approach to CDI prevention

  35. Targeted Assessment for Prevention (TAP) Strategy CDI TAP reports available in NHSN Work ongoing to use CO-CDI and other data sources to identify CDI cases from nursing homes and other community sources www.cdc.gov/hai/prevent/tap.html

  36. CDI Risk Assessment Dubberke et al. Infect Control Hosp Epidemiol 2014; 35(6):628-645. www.cdc.gov/hai/prevent/tap.html • Conduct a risk assessment annually and whenever CDI goals are not met1 • Use CDC’s Targeted Assessment for Prevention (TAP) Strategy • Pairing the results of a CDI facility assessment with the CDI Implementation Tool allows facilities to implement infection prevention strategies that most directly meet their needs.

  37. CDI Case Review The CDI Implementation Tool includes a template for CDI Case Review Dubberke et al. Infect Control Hosp Epidemiol 2014; 35(6):628-645.www.cdc.gov/hai/prevent/tap.html Review each CDI case (e.g., root cause analysis) Examine temporal and spatial relationships between cases to determine units at risk for transmission due to community-onset or hospital-onset CDI cases.

  38. A Coordinated Response A coordinated response is more effective than independent efforts1 Partners in Prevention: The state and local health department and other state partners can assist and provide opportunities to extend efforts across the continuum of care Figure from CDC Vitals Signs: http://www.cdc.gov/vitalsigns/stop-spread/index.html • Slayton et al. MMWR 2015; 64(30): 826-831.

  39. Communication During Patient Transfer of Multidrug-Resistant Organisms (MDROs) Effective Jan 2014, OAR 333-019-0052 requires facilities to notify in writing receiving institution that patient is infected or colonized with MDRO requiring transmission-based precaution in addition to standard precautions Examples: CRE, MRSA, C. diff Typically require additional precautions such as wearing mask, gown and gloves with patient contact, in some cases, patient isolation

  40. Template form

  41. IFT rule implementation • OR hospitals and SNFs surveyed in 2015 & 2016 # of facilities surveyed: 60 55 140 134

  42. IFT rule implementation “We notify receiving facilities of MDROs at discharge” “Transferring facilities notify us of MDROs”

  43. What is your facility doing?

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