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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
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
2
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
3
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
4
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
5
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
6
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
8
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
9
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
10
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
11
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
12
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
13
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
14