Preventing Clostridium difficile. July 13,

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Preventing Clostridium difficile Infection (CDI) July 13, 2011 1

Learning Objectives: Identify recent changes in the epidemiology of CDI, including transmission i and risk ikpopulations. Review recent research on prevention of healthcare associated itdcdi. Discuss how to apply accepted infection prevention practices for CDI in healthcare settings. July 13, 2011 2

Today s Didactic Session Presentation Microbiology and Pathogenesis Epidemiology and National trends Diagnostic issues Major modifiable risk factors Environmental and transmission i prevention issues Antibiotic Stewardship CDC Prevention strategies July 13, 2011 3

Microbiology Gram positive, spore forming rod Obligate anaerobe Toxin A and Toxin B Required to cause disease C. difficile infection (CDI, formerly CDAD) Antibiotic exposure most important risk factor Primarily healthcare associated pathogen Fecal oral transmission? Brought in from the community July 13, 2011 4

http://www.shea online.org/about/compendium.cfm July 13, 2011 5

CDI Incidence and Cost Hospital onset: 165,000 cases, $1.3 3billion in excess costs, and 9,000 deaths annually Nursing home onset: 263,000 cases, $2.2 billion in excess costs, and 16,500 deaths annually Community onset, onset healthcarefacility associated: 50,000 cases, $0.3 billion in excess costs, and 3,000 deaths annually Campbell et al. Infect Control Hosp Epid. 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 July 13, 2011 6

Mortality due to C. difficile Infection per 100,000 000 population, Massachusetts http://wonder.cdc.gov/mortsql.html July 13, 2011 7

C Difficile Rates in 35 Hospitals Vary Widely 25 TD20 R ATE / 1 0,000 P 15 10 5 0 P Carling 2002 July 13, 2011 8

Current relatively epidemic strain of C. difficile Name NAP1 or ribotype 027 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 5 Akerlund et al. J Clin Microbiol. 2008;46:1530 3 July 13, 2011 9

Pathogenesis of C. difficile Infection (CDI) Key steps Acquisition of C. difficile Alteration of colonic flora Growth of C. difficile and elaboration of toxins Poorly understood additional factor (s?) July 13, 2011 10

Antimicrobials Predisposing to CDI Very Commonly Related Clindamycin Ampicillin Amoxicillin Cephalosporins Fluoroquinolones Less Commonly Related Other penicillins Sulfonamides Trimethoprim Cotrimoxazole Macrolides Carbapenems Uncommonly Related 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. 2449 July 13, 2011 11

C. difficile Diagnostics Test Advantages) Disadvantages) Toxin testing Enzyme Rapid, simple, inexpensive Lesssensitive sensitive than tissueculture immunoassay cytotoxicity assay, some detect only toxin A Tissue culture cytotoxicity ii Organism identification More sensitive than enzyme immunoassay Detects toxin B primarily; labor intensive; requires 24 48 48 hours for a final result, special equipment Dt Detection ti of Rapid, sensitive, may Not specific, toxin testing ti required dto glutamate prove useful as a triage or verify diagnosis dehydrogenase screening tool PCR Rapid, sensitive, detects Cost, special equipment, may be presence of toxin gene oversensitive Stool culture Most sensitive test available when performed appropriately May be associated with false positive results if isolate is not tested for toxin; labor intensive; requires 48 96 hours for results July 13, 2011 12

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) Promotedto to enhance sensitivity Actually enhances positive predictive value of confirmatory test Increased prevalence of disease July 13, 2011 13

Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds? Gastricacid acid suppression July 13, 2011 14

Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds? Gastricacid acid suppression Major modifiable risk factors July 13, 2011 15

Major Modifiable Risk Factors July 13, 2011 16

Major Modifiable Risk Factors July 13, 2011 17

Major Modifiable Risk Factors Antibiotic Exposure Acquisition of C. difficile July 13, 2011 18

Major Modifiable Risk Factors Antibiotic Exposure Antibiotic Stewardship Acquisition of C. difficile Optimizing Environmental Cleaning and Hand Hygiene July 13, 2011 19

Antimicrobial Stewardship Regardless of setting, ~ 50% antibiotic use is inappropriate No need for antibiotics (25%) Wrong antibiotic or duration (25%) Potential to be best CDI preventative measure Decrease in number of patients at risk Decrease in number of patients with CDI (colonization pressure) July 13, 2011 20

Anecdotal situations and examples 25 Focused Antibiotic Restriction Can Work Quinolone restriction New housekeeping company Num mber of Ca ases 20 15 10 Beginning i of outbreak period Quinolone restriction partially lifted 5 0 2004 2005 2006 2007 Jul Sep Nov Jan Mar May Jul Sep Nov Jan Month and Year Mar May Jul Sep Nov Jan Mar July 13, 2011 21

Daily Dos ses Nimber of Defined Impact that Restricting Fluoroquinolones has on Reducing Unnecessary Antimicrobial Use Quinolones 2000 1500 1000 500 Quinolone Restriction Period 0 Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecJan Feb Mar 2005 2006 2007 Month and Year Kallen, et al. 18th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 6, 2008; Orlando, FL.

1980 2003 = 309 Studies 66 Studies had meaningful data analysis 16 Studies evaluated microbiologic outcomes 4 Studies Favorable 8 Studies +/- 4 Studies no effect July 13, 2011 23

Antimicrobial Stewardship Impact on C. difficiledisease July 13, 2011 24

C. difficile and the Environment Level of contamination may be high Spores survive > 5 months Infective dose < 10 spores July 13, 2011 25

C. Difficile and the Environment 100 S kin Co ntamin ation % 80 60 40 20 0 78 64 SKIN - ANY GROIN CHEST/ABDOMEN 20 Patients with CDAD Asymptomatic Carriers Non carriers Sethi et al. 2010 July 13, 2011 26

C. Difficile and the Environment mental Contamin nation % Environ 100 80 60 40 20 0 78 Patients with CDAD 60 Asymptomatic Carriers ENVIRONMENT ANY CALL BUTTON BED RAIL TABLE TELEPHONE 30 Non carriers Sethi et al. 2010 July 13, 2011 27

C. Difficile and the Environment OUNTS/1 0cm 2 PCR CO LONY C 6000 3000 0 PT HANDS NEAR ENVIRONMENT CDAD POS. PATIENT ROOMS CDAD NEG. PATIENT DISTANT ENVIRONMENT HCW HANDS July 13, 2011 28

Is the environment important in C. difficile Transmission? i July 13, 2011 29

C. difficile Transmission from Prior Room Occupants LOPING CDAD D % RISK OF DEVE 20 10 110% Increased risk Shaugnessey etal. Abstract K-4194 IDSA / ICAAC. October 2008 0 FORMER CDAD OCCUPANCY NO PRIOR CDAD OCCUPANCY July 13, 2011 30

Can Disinfection Cleaning Decrease Environmental Contamination? ti July 13, 2011 31

Studies reporting a favorable impact of enhanced environmental hygiene during a CDI outbreak 4 PORTS PUBL LISHED RE 3 2 1 0 < 1996 1996 1998 2000 2002 2004 2006 2008 July 13, 2011 32

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 July 13, 2011 33

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

Can improved disinfection/cleaning lead to decreased d CDI? July 13, 2011 35

Greater New York CDI Collaborative 40 Hospitals New York area, 2007 2009 Pre intervention rate 8.1/ 10,000 PtD Similareducation, 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. July 13, 2011 36

Prevention Strategies Core Strategies High levels of scientific evidence Demonstrated feasibility Supplemental Strategies Some scientific evidence Variable levels of feasibility Gould - CDC July 13, 2011 37

Core Environmental Cleaning Supplemental Cleaning and disinfection Reassess adequacy of of equipment and room cleaning and environment address issues Consider sodium Use sodium hypochlorite (bleach) hypochlorite in outbreak containing agents orhyper endemic settings Routinely assess adherence to protocols and adequacy of cleaning www.cdc.gov/ncidod/dhqp/id_cdifffaq_hcp.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81 9229 92 Cohen et al. Infect Control Hosp Epidemiol 2010;31 July 13, 2011 38

So what about bleach? Recommended by CDC when there is evidence of ongoing transmission Pro: Sporicidal (but slow to get > 4 log kill) May have benefit in outbreak settings New Peroxide/Acetic Acid disinfectants Sporicidal claim = bleach Con: Difficult to use Hard on the environment and staff Lower concentrations work poorly No clinical studies to compare with optimized routine disinfection cleaning July 13, 2011 39

Core Contact Precautions Supplemental Gloves/gowns on room Extend use of Contact entry Precautions beyond Private room (preferred) or duration of diarrhea cohort with dedicated (hospitalization) commodes Presumptive isolation Dedicated equipment Maintain for duration of diarrhea Measure compliance Universal glove use on units with high CDI rates Intensifyassessment of compliance July 13, 2011 40

Rationale for considering extending isolation beyond duration of diarrhea Bobulsky et al. Clin Infect Dis 2008;46:447 50 July 13, 2011 41

Consider universal glove use on units with high CDI rates Asymptomatic carriers may have a role in transmission (magnitude uncertain) Practical screening tests not available July 13, 2011 42

Hand Hygiene Core Hand hygiene based on CDC or WHO guidelines Soap and water preferentially in outbreak or hyper endemic settings Supplemental Soap and water for hand hygiene before exiting room of a patient with CDI Intensify assessment of compliance Measure compliance July 13, 2011 43

Method of Hand Hygiene Oughton M. ICAAC Meeting, 2007. Abstract K-1376a. July 13, 2011 44

Hand Washing: Product Comparison Product Log10 Reduction Tap Water 0.76 4% CHG antimicrobial hand wash 0.77 Non antimicrobial hand wash 078 0.78 Non antimicrobial body wash 0.86 0.3% triclosan antimicrobial hand wash 0.99 Heavy duty hand cleaner used in manufacturing environments 1.21* * Only value that was statistically better than others Conclusion: Spores may be difficult to eradicate even with hand washing Emphasizes need for absolute adherence with glove use Edmonds, ds, et al. a. Presented at: SHEA 2009; Abstract 43 Johnson et al. Am J Med 1990;88:137 40 July 13, 2011 45

Diagnostic Testing Core Laboratory based alert system for immediate notification of positive test results Supplemental Evaluate and optimize i testing for CDI July 13, 2011 46

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 these judiciously i 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. July 13, 2011 47

Preventing CDI Infections Conclusions CDI is the most serious, frequent and costly HAI. All hospitals should be in compliance with CDC Core Recommendations. Optimizingenvironmental hygiene isbecoming recognized as central to controlling CDI. Decreased antibiotic exposure and stewardship optimization are important. July 13, 2011 48