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Epidemiology and Prevention of Clostridium difficile W.I.P.E. Out Those Bugs May 2, 2014 Kavita K. Trivedi, MD Principal, Trivedi Consults, LLC Adjunct.

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Presentation on theme: "Epidemiology and Prevention of Clostridium difficile W.I.P.E. Out Those Bugs May 2, 2014 Kavita K. Trivedi, MD Principal, Trivedi Consults, LLC Adjunct."— Presentation transcript:

1 Epidemiology and Prevention of Clostridium difficile W.I.P.E. Out Those Bugs May 2, 2014 Kavita K. Trivedi, MD Principal, Trivedi Consults, LLC Adjunct Clinical Professor of Medicine, Stanford University School of Medicine

2 Objectives Describe the changing epidemiology of Clostridium difficile infections (CDI) in the United States Review recent research on prevention of CDI Discuss how to apply accepted infection prevention practices for CDI in healthcare settings

3 Background Gram positive, spore forming rod Obligate anaerobe Toxin A and Toxin B Required to cause disease Clostridium difficile infection (CDI, formerly CDAD) Most common cause of healthcare- associated diarrhea Fecal-oral transmission Can be community-associated

4 Background: Adults 2-5% of healthy adults have C. difficile colonization of the colon 20-40% of hospitalized adults are colonized with C. difficile 4

5 Background: Children Colonization rates of up to 70% have been reported in children < 1 year By 2 years the ‘normal’ colonic flora is established and colonization decreases to the rate of healthy adults 5

6 Epidemiology Range from mild to severe Starting in 2002, changes in C. difficile noted, first in Quebec Increased incidence (1991/1992  2003) – 36/100,0000  156/100,000 – 65 and older: from 102/100,000 to 866/100,000 Increased complications – Complicated disease: 7.1%  18.2% – Death within 30 days: 4.7%  13.8% Lisa Winston, MD; Pepin et al., CMAJ 2004;171:466-72


8 C. Difficile Infection (CDI) Incidence and severity have increased with dissemination of BI/NAP1 isolates – Historically uncommon – epidemic since 2000 – Increased virulence Increased toxin A and B production Polymorphisms in binding domain of toxin B Increased sporulation – Increased resistance to fluoroquinolones Higher MICs compared to historic strains and current non- BI/NAP1 strains – Early diagnosis and treatment are required to reduce morbidity/mortality 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


10 Clostridium difficile Incidence and Mortality Are Increasing 10 Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April 2008. Available at: Accessed March 10, 2010. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419. No. of CDI Cases per 10,000 Discharges Annual CD-related Mortality Rate per Million Population

11 Cost of CDI in US CDI accounts for 336,000 hospitalizations annually Aggregate hospital costs exceed $8.2 billion annually Patients with principal CDI diagnosis remain hospitalized for 6.9 days at a cost of $10,100/stay –Patients with secondary CDI diagnosis remain hospitalized for 16.0 days at a cost of $31,500/stay. CDI disproportionately affects the elderly –CMS pays for 68% of CDI hospital stays Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009. HCUP Statistical Brief124. January 2012. Rockville, MD: Agency for Healthcare Research and Quality. http://www.hcup- Accessed December 27, 2011.

12 Pathogenesis of CDI Key steps Acquisition of C. difficile Alteration of colonic flora Growth of C. difficile and elaboration of toxins Poorly understood additional factor (s?) Gerding D N, Johnson S. CID 2010;51:1306-1313

13 CDI Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds ? Gastric acid suppression

14 Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds ? Gastric acid suppression Major modifiable risk factors

15 C. difficile Hospital Epidemiology Use of antibiotics is frequent Environmental contamination by C. difficile is common – Spores are difficult to eradicate Personnel carry C. difficile on their hands Asymptomatic patients carry C. difficile

16 Major Modifiable Risk Factors Gerding D N, Johnson S. CID 2010;51:1306-1313

17 Major Modifiable Risk Factors Antibiotic Exposure Antibiotic Stewardship Acquisition of C. difficile Optimizing Environmental Cleaning and Hand Hygiene

18 Antimicrobial Stewardship

19 Antibiotic misuse adversely impacts patients - Clostridium difficile Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile associated disease (CDAD) Up to 85% of patients with CDAD have antibiotic exposure in the 28 days before infection 19 Chang HT et al. Infect Control Hosp Epidemiol 2007; 28:926–931.

20 Antimicrobials Predisposing to CDI Very Commonly Related Less Commonly Related Uncommonly Related Clindamycin Ampicillin Amoxicillin Cephalosporins Fluoroquinolones Other penicillins Sulfonamides Trimethoprim Cotrimoxazole Macrolides Carbapenems Aminoglycosides Bacitracin Metronidazole Teicoplanin Rifampin Chloramphenicol Tetracyclines Daptomycin Tigecycline Bouza E, et al. Med Clin North Am. 2006;90:1141-1163. Loo VG, et al. N Engl J Med. 2005;353:2442-2449.

21 Impact of Fluoroquinolone Optimization on Rates of Hospital-Onset CDI 21 HO-CDAD cases/1,000 pd Month and Year Infect Control Hosp Epidemiol. 2009 Mar;30(3):264-72. 2005 20062007

22 1980 – 2003 = 309 Studies 66 Studies had meaningful data analysis 16 Studies evaluated microbiologic outcomes 4 Studies – Favorable 8 Studies +/- 4 Studies—no effect

23 Antimicrobial Stewardship Impact on C. difficile Disease

24 ASP Make a Difference with Hospital- Associated CDI Tertiary Care Hospital; Québec, Canada (2003-2006) Valiquette, et al. Clin Infect Dis 2007;45:S112. 24

25 ASP Community Hospital Example Team: ID pharmacists, ID physicians Target: 8 target antimicrobials Interventions: Prospective audit of new antimicrobial starts and weekly use Measure: Significant reductions in Clostridium difficile rates, antimicrobial utilization and pharmacy costs Malani, AN et al. Clinical and economic outcomes from a community hospital's antimicrobial stewardship program. American Journal of Infection Control 2012 May 9.

26 Environmental Cleaning

27 C. difficile and the Environment Level of contamination may be high Spores survive > 5 months Infective dose < 10 spores

28 C. Difficile and the Environment Sethi et al. 2010

29 C. Difficile and the Environment Sethi et al. 2010

30 C. Difficile and the Environment

31 Is the environment important in C. difficile transmission?

32 Persistence of spores Shaugnessy et al. Infect Control Hosp Epidemiol. 2011 Mar;32(3):201-6. In multivariate analysis, OR for prior room occupant with CDI = 2.4 (1.2-4.5) Adjusted for age, APACHE score, PPI, abx use… but not for length of stay

33 Can disinfection cleaning decrease environmental contamination?

34 Studies reporting a favorable impact of enhanced environmental hygiene during a CDI outbreak

35 Culture based evaluation - Pre-intervention - after routine terminal cleaning - after terminal cleaning by the research staff - following education of the ES staff and administrative interventions

36 Percentage of C. difficile-positive cultures n=9 rooms 80 70 60 50 40 30 20 10 0 Percent positive Before cleaning After housekeeping cleaning After disinfection by research team* Bedrail Bedside table Phone Call button Toilet Door handle Eckstein et al, BMC Infect Dis. 2007 Jun 21;7:61. *Similar results found after ES cleaning following interventions

37 Can improved disinfection/cleaning lead to decreased CDI?

38 Greater New York CDI Collaborative 40 Hospitals – New York area, 2007-2009 Pre-intervention rate – 8.1/ 10,000 PtD Similar education, check sheet and self reporting of thoroughness of terminal cleaning. Glitterbug lotion used for some teaching (not monitoring). 70% of Hospitals saw an average decrease of 26% in HO CDI (Mean for the system = 15%) Source: Barbra Smith, RN CIC and Brian Koll, M.D. project Coordinators. APIC presentation.

39 Prevention Strategies

40 CDC Prevention Strategies High levels of scientific evidence Demonstrated feasibility Some scientific evidence Variable levels of feasibility Core Strategies Supplemental Strategies

41 Environmental Cleaning Core Supplemental Cleaning and disinfection of equipment and environment Consider sodium hypochlorite in outbreak or hyper endemic settings Routinely assess adherence to protocols and adequacy of cleaning Reassess adequacy of room cleaning and address issues Use sodium hypochlorite (bleach) – containing agents Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31

42 Contact Precautions CoreSupplemental 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 (hospitalization) Presumptive isolation Universal glove use on units with high CDI rates Intensify assessment of compliance

43 Hand Hygiene Core Hand hygiene based on CDC or WHO guidelines Soap and water preferentially in outbreak or hyper endemic settings Measure compliance Supplemental Soap and water for hand hygiene before exiting room of a patient with CDI Intensify assessment of compliance

44 Diagnostic Testing CoreSupplemental Laboratory-based alert system for immediate notification of positive test results Evaluate and optimize testing for CDI

45 Evaluate and Optimize Testing for CDI Toxin A/B enzyme immunoassays have low sensitivities (60-80%) Despite high specificity, poor test ordering practices (i.e. testing formed stool) may lead to false positives Consider more sensitive diagnostic paradigms but apply judiciously Restrict testing to unformed stool only Focus testing on patients with > 3 unformed stools within 24 hours Repeat testing no more than every 5-7 days if negative Require expert consultation for repeat testing within 5 days Test of cure is not recommended Peterson et al. Ann Intern Med 2009;15:176-9. Cohen et al. Infect Control Hosp Epi 2010; 31 (5): 431-455.



48 Two-Step Testing Utility related to Sensitivity of initial screen Sensitivity of GDH EIA screen 76% to 100% Cost of confirmatory test alone versus screen plus confirmatory test Cost of false positive test (not quantified) Promoted to enhance sensitivity Actually enhances positive predictive value of confirmatory test Increased prevalence of disease

49 Conclusions CDI is the most serious, frequent and costly HAI Decreased antibiotic exposure and stewardship optimization are important in preventing CDI Optimizing environmental hygiene is becoming recognized as central to controlling CDI All hospitals should be in compliance with CDC Core Recommendations

50 CDI and Infection control Gloves + gowns for duration of diarrhea Wash with soap and water (epidemic setting) Private rooms – Dedicated commode Bleach cleaning Antimicrobial stewardship Cohen et al., Infection Control and Hospital Epidemiology, 2010; 31: 431-455

51 Conclusions Gerding D N, Johnson S. CID 2010;51:1306-1313

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