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Clostridium Difficile Update
Transmission, Prevention, Treatment Maggie Hagan, M.D.
1
C. Diff Colitis
• History – Described in 1935 by Hall and O Toole – Named the Difficult Clostridium – Found to colonize healthy newborns – Found to be toxigenic – 1978 C diff. Toxin found in the stool of patients
with antibiotic associated diarrhea
2
Heron et al. Natl Vital Stat Rep 2009;57(14). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf
Background: Impact 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
1999 2003
Rate
2000 2004 2001 2005 2002 2006 Year
Male Female White Black Entire US population
Heron et al. Natl Vital Stat Rep 2009;57(14). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf
Background: ImpactAge-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
1999 2003
Rate
2000 20042001 20052002 2006Year
MaleFemaleWhiteBlackEntire US population
3
Epidemiology of C diff
• Prevalence of asymptomatic colonization 7-50% of adult inpatients in acute care
• 5-7% among adults in long term care • Risk of colonization increases during
hospitalization
4
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
1
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Changing Epidemiology of C diff
• Estimated 500,000 cases of C diff/year in US • Estimated 15,000-20,000 deaths/year • Community C diff 7.6 cases/100,000 person
years • 35% have had no antibiotics within 42 days
Nature. 2009:7;526-36
5
Changing Epidemiology of C diff
• Beginning in 2001 there was an abrupt increase in hospital discharges listing C diff as a diagnosis
• 5 fold increase in patients >65 • Strain termed NAP1/BI/027 • Increase in cases in healthy people/outpatients
Critical Care 2008, 12:203
6
Pathogenesis of C diff
• A “two hit”phenomenon – Colonization with C diff – Alteration of gut flora with antibiotics
7
Pathogenesis of C diff
• Oral ingestion of C diff spores • Spores germinate into vegetative form in small
intestine • Disruption of commensal flora of intestine
allows C diff to flourish • C diff produces two exotoxins: Toxin A and
Toxin B Critical Care 2008, 12:203
8
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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C diff Outbreaks
Three Factors Implicated – Increased production of Toxins A and B – Floroquinolone resistance – Production of a binary toxin
N Engl J Med. 2008: 359;18
9
Toxin Production in Epidemic Strains of C diff
N Engl J Med. 2008: 359;18 10
Pathogenesis of C diff
Nature. 2009:7;526-36 11
Pathogenesis of C diff
Nature. 2009:7;526-36 12
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Risk Factors for C diff
• Advanced age • Duration of hospitalization • Exposure to antibiotics • Chemotherapy • HIV • GI surgery • Acid suppression
13
Clinical Manifestations of C diff
• Range from asymptomatic to fulminant disease
• Diarrhea • Fever • Abdominal pain • Leukocytosis • May have abdominal pain/distention without
diarrhea in advanced disease
14
Clinical Manifestations of C diff
• Incubation period from acquisition of C diff to CDI is short (median2-3 days)
• Patients may remain at risk for C diff for 3 months or longer after they have stopped antibiotics
MMWR Morb Mortal Wkly Rep 2012;61:157-162. 15
Diagnosis of C difficile Infection
• Testing should be performed only on diarrheal stool, unless ileus due to C diff is suspected
• Only a single specimen needed for testing • PCR testing is rapid, sensitive and specific • EIA testing for C diff toxin A and B is rapid but less
sensitive • Repeat testing during the same episode of
diarrhea is discouraged • No “test of cure”
Infect Control Hosp Epidemiol 2010; 31,431-55. 16
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Transmission of C diff
CID 2010:50:1458-61 17
Factors Associated with Increased Shedding of C diff
• Diarrhea • Fecal incontinence • High concentrations of organisms in the stool • “super shedders”
18
Environment as a Source of Transmission of C difficile
• C diff is commonly isolated from the hands of health care providers
• The frequency of positive hand cultures is strongly correlated to the level of environmental contamination
• Hands 0% when Environment 0-25% • Hands 8% when Environment 26-50% • Hands 36% when Environment >50%
Am J Infect Control 2010;38:S25-33. 19
Environment as a Source of Transmission of C difficile
• Acquisition of spores on gloved hands occurred as frequently after contact with environmental surfaces as after contact with skin sites (50% vs 50%)
• Prior room occupant with C diff is a significant risk factor for C diff acquisition (11% vs 5%)
1). Guerrero DM, et al. Am J Infect Control 2011 2). Shaughnessy MK, et al. Infect Control Hosp Epidemiol 2010;32:210-6
20
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Environmental Sources of C difficile
• Electronic thermometers • Blood pressure cuffs • Bedside commodes • Stethoscopes
21
What Makes C diff Different From Other Bacteria?
22
23
Infection Control Measures for C diff Infection
• Gowns and gloves for contact with patients • Wash hands with soap and water • Private room or cohort patients with private
commode • Chlorine containing cleaning agents, terminal
cleaning of rooms • Antibiotic restraint
24
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Special Approach to Prevent C diff Transmission
• Expedite identification and isolation of patients
• Prolong duration of contact precautions • Improve bathing to reduce the burden of
spores on skin • Daily disinfection of high-touch surfaces
during C diff treatment • Use more sensitive diagnostic tests
25
Cleaning of High Touch Surfaces Daily
26
Environmental Cleaning to Control C diff
CDC, SHEA, IDSA all recommend use of a 1:10 dilution of sodium hypochlorite for environmental disinfection in outbreak settings of C diff
Am J Infect Control 2010;38:S25-33.
27 28
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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29 30
UV Light and C diff
31
Use of UV Light to Control C diff
• Numerous retrospective studies funded by industry
• Recent prospective study looking at environmental cultures
32
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Use of UV Light to Control C diff
Infect Control Hosp Epidemiol. May 2013; 34(5): 466–471. 33
Hand Hygiene for C diff
• C diff in its spore form is highly resistant to killing by alcohol
• Spores can be physically removed by soap and water
• Several studies have documented reduction in C diff rates by improvement in hand washing compliance
Infect Control Hosp Epidemiol. 2009 Oct;30(10):939-44.
Infect Control Hosp Epidemiol 2010;31:565–570.
34
C diff on Hands of HCWs • Compared hand contamination
• 66 HCW caring for patients with CDI • 44 HCW controls • Monitored for 8 weeks
• Results • C diff spores on 24% of samples of hands from HCWs
caring for CDI patients • No spores on hands of control HCWs
• Nursing assistants had highest rates • Most of HCWs used gloves for patient contact
Infect Cont and Hosp Epidemiol. January 2014;35 (1): 10-15 35
Summary of Prevention Measures
• Contact Precautions for duration of illness
• Hand hygiene in compliance with CDC/WHO
• Cleaning and disinfection of equipment and environment
• Laboratory-based alert system
• CDI surveillance • Education
• Prolonged duration of Contact Precautions*
• Presumptive isolation • Evaluate and optimize
testing • Soap and water for HH upon
exiting CDI room • Universal glove use on units
with high CDI rates* • Bleach for environmental
disinfection • Antimicrobial stewardship
program
Core Measures Supplemental Measures
* Not included in CDC/HICPAC 2007 Guideline for Isolation Precautions 36
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Measures to Improve C diff Rates
• Analyze rates • Form a multidisciplinary performance
improvement team – Environmental cleaning – Proper PPE – Hand washing – Antibiotic stewardship
37 38
39
Treatment of C diff Infection
• Metronidazole • Vancomycin • Fidaxomicin • Probiotics • Immunoglobulin • Fecal Transplant
40
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Treatment of C diff Infection
• Metronidazole is the drug of choice – 500mg tid for 10-14 days
• Vancomycin drug of choice for severe infection – 125-500mg qid for 10-14 days – Tapering schedule for recurrent infections
• Severe/Complicated C diff Vancomycin 500mg po q 6 hours and Metronidazole 500mg IV q 8 hours
Infection Control and Hospital Epidemiology, Vol. 31, No. 5 (May 2010), pp. 431-455 41
Metronidazole vs Vancomycin
N Engl J Med. 2008: 359;18 42
Fidaxomicin vs Vancomycin
• A multicenter, prospective, randomized, placebo controlled trial
• 629 patients enrolled at 52 sites • No difference in cure rates • Treatment with Fidaxomicin associated with
lower rate of recurrence (15.4 vs 25.3%) • Cost issues
N Engl J Med 2011; 364:422-431 43
Treatment of C diff Infection
• Vancomycin enema • Fecal transplant • Colectomy
44
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Fecal Transplantation
• Treating Clostridium difficile Infection With Fecal Microbiota Transplantation
• Obtain donor stool from a relative • Screen donor for C diff • Mix donor stool with tap water to make an solution • Instill as an enema to the patient
• Via Christi has a protocol for FMT • Requires specific consent form
Clin Gastro and Hepatol. , December 2011.9(12) 1044-1049
45 46
Probiotics in the Treatment of C diff
• Current C diff guidelines do not recommend use of probiotics
• Cochrane review 2008 reviewed 4 studies and found a statistically significant benefit in only one small study
• More recent studies of multi-strain probiotics show promise
47 48
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Role of Immunotherapy in the Treatment of C diff
• Inability to mount an immune response appears to make patient susceptible to recurrent infections
• Favorable outcomes with use of IgG for recurrent infections
• No randomized controlled trials • Vaccine for C diff is being studied
49 Nature. 2009:7;526-36 Nature. 2009:7;526-36 50
Immune Response to C diff
N Engl J Med. 2008: 359;18 51
Treatment of C diff
• Check IgG level on patients with severe or recurrent C diff
• Give a one-time dose of IVIG to patients with low IgG
52
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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Role of Antibiotic Stewardship in Controlling C diff
• Use of antibiotics is associated with increase in C diff rates
• Certain antibiotics are associated with higher C diff rates (floroquinolones)
• Several studies have shown reductions in C diff rates with effective antimicrobial management programs
53
Clostridium Difficile Treatment and Transmission Margaret Hagan, MD
Family Medicine Winter Symposium December 5, 2014
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