Transcript Clostridium difficile infection

CLOSTRIDIUM DIFFICILE
INFECTION
Kelly Strine
FNP-S
NUR 652
DEFINITION
 Clostridium dif ficile (C -dif f) is a gram -positive, spore -formi ng anaerobic
bacillus.
 C-dif f was initially detected in 1935 in the stool of newborns and was
considered nonpathogenic.
 It is spread by ingesting the spore through the fecal oral route.
 Infection and colonization is usually linked to the use of broad -spectrum
antibiotic within 1 2 weeks, proton pump inhibitor s, H2 antagonists,
chemotherapy, increasing age and hospitalization.
 It is characterized by the presence of 3 or more unformed, diarrheal stools
in 24 or fewer consecuti ve hour s, a stool test result positive for the
presence of toxigenic C -dif f or its toxins, pseudomembranous colitis.
 Reinfection is common and is seen in 25% of cases treated with oral
antibiotics. Once a relapse has occurred, second relapse is 45%.
(Lessa, Gould, and McDonald, 2012), (Kelly & LaMont, 2013)
ETIOLOGY
 C dif ficile colitis results from a disruption of the normal
bacterial flora of the colon, ingestion of a C-Dif f causing
spore, colonization with C dif ficile, and release of toxins that
cause mucosal inflammation, mucosal damage, and diarrhea .
 It is the only bacteria noted to be caused by the use of
antibiotics.
(Aberra & Katz, 2013)
PATHOPHYSIOLOGY
 Colonization occurs from ingestion of C -dif f spores via fecal
oral route. Colonization can occur and patients can remain
asymptomatic (Carriers). As many as 2 -3% of healthy adults
and 70% of healthy infants are carriers.
 During a disruption in the intestinal microbiota, such as the
use of broad spectrum antibiotics, the bacteria has an
opportunity to proliferate.
 Toxins are produced during this time of proliferation causing
colitis, diarrhea, and abdominal pain.
(Aberra & Katz, 2013)
PATHOPHYSIOLOGY
 Two distinct toxins have been seen in C -diff infections (CDI), toxin
A and toxin B. These toxins are associated with approximately
75% of C-diff strains.
 Both toxins are proteins capable of binding to specific receptors
on the intestinal mucosal cells where they gain entry to the cells.
The toxins produce inflammation of the mucosa and secrete a
protein rich exudate that contains neutrophils, monocytes and
slough enterocytes. They are responsible for activating cytokine
release from the monocytes. (Hamm, 2000)
 A hypervirulent strain of C-diff, NAP1 is the most serious strain.
This strain produces 16 fold higher concentrations of toxin A and
23 fold higher concentrations of toxin B. This strain is also
characterized by a binary toxin. The pathogenesis of the binary
toxin is unclear but it is thought that the synergistic effect of
these toxins is what produces more severe symptoms.
(Aberra & Katz, 2013)
PATHOGENESIS OF CDI
1. Ingestion
of spores transmitted
from other patients
via the hands of healthcare
personnel and environment
3. Altered lower intestine flora
(due to antimicrobial use) allows
proliferation of
C. difficile in colon
4. Toxin A & B Production
leads to colon damage
+/- pseudomembrane
2. Germination into
growing (vegetative)
form
(Sunenshine et al, 2006)
RISK FACTORS
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Recent hospitalization
Recent use of broad spectrum antibiotics
Age greater than 65
Gastrointestinal surgery
Nasogastric tube feeding
Reduced gastric acid secretion
Concurrent disease such as Inflammatory Bowel Syndrome
Impaired immunity
Comorbidities that cause use of additional antibiotics
(Henrich, Krakower, Bitton & Yokoe, 2009), (Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
INCIDENCE
 The incidence of C -dif f has increased across the United States, Canada
and Europe. In 2008 it was repor ted that 8.75 per 1000 discharges in
28 southern United States community hospitals had C -dif f listed as a
diagnosis.
 It accounts for 20 -30% of cases of antibiotic -associated diarrhea and is
the most commonly associated cause of infectious diarrhea in the
healthcare setting.
 In 2008 the incidence of C -dif f in a sur vey of US health -care facility
inpatients was 13.1/10,000. Of those individuals, 70% was older than
60.
 According to the Center for Disease Control and Prevention,
approximately 337,000 cases of CDI are repor ted each year, causing
14,000 deaths.
 In the out patient setting the rate is approximately 7.7 cases per
100,000 per son -years.
(Lessa, Gould & McDonald, 2012)
CLINICAL FINDINGS
 Mild to moderate infection
 Watery diarrhea three or more times a day for two or more days
 Mild abdominal cramping and tenderness
 Severe infection
 Watery diarrhea 10 to 15 times a day
 Abdominal cramping and pain, which may
be severe
 Fever
 Blood or pus in the stool
 Nausea
 Dehydration
 Loss of appetite
 Weight loss
 Swollen abdomen
 Kidney failure
 Increased white blood cell count
Pseudomembranous Colitis
(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
(Aberra & Katz, 2013)
DIFFERENTIATION OF DISEASE SEVERIT Y
 Possible severe disease criteria
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WBC > 15,000 cells/microL
Creatinine level > or =1.5 times the premorbid level
More than 10 bowel movements per day
Severe abdominal pain
 Scoring System
 1 point given for age >60, temp > 38.3 degrees Celsius, serum
albumin <2.5 mg/dL, or WBC count >15,000 cells/microL.
 2 points for endoscopic evidence of pseudomenbranous colitis or
treatment in the ICU.
 If 2 or more points, consider severe disease
(Kelly & LaMont, 2013)
COMPLICATIONS
 Dehydration
 Electrolyte Imbalances
 Kidney Failure
 Toxic Megacolon
 Bowel Perforation
 Death
(Aberra & Katz, 2013)
DIFFERENTIAL DIAGNOSIS
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Food poisoning
Enteric infections
Antibiotic-associated diarrhea
Crohn’s Disease
Diverticulitis
Viral Gastroenteritis
Intra-abdominal Sepsis
Irritable Bowel Syndrome
Malabsorption
Salmonellosis
Shigellosis
Ulcerative Colitis
Vibrio Infections
(Domino, 2013)
SCREENING
 Screening is not recommended for asymptomatic individuals
 Individuals should only be tested for C -Dif f if they have 3 or
more watery, unformed stools per day or are have a suspected
ileus due to C-dif f.
(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
(Surawicz, .Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)
LABORATORY TESTS
 Stool Culture for toxin -producing C-dif f (*Gold Standard*)
 Most accurate for diagnosis but due to slow turn around times of up
to 3 days, it is not clinically feasible.
 Nucleic Acid Amplified Tests (NAAT) including Polymerase
Chain Reaction (PCR)
 PCR testing has high sensitivity and high specificity. This may lead
to false-positive results. This test is only recommended in patients
with acute disease.
 Enzyme Immunoassay (EIA)
 Rapid results but low sensitivity with high specificity.
 Glutamate Dehydrogenase (GDH)
 GDH is an enzyme for produced by C-diff in large amounts with toxins
A and B. It is sensitive in detecting but is not specific for C -diff.
(Bartlett, 2010), (Belanger, Boissinot & Clairoux, 2003), (Carroll, 2011), (Humphries, Uslan & Rubin,
2012), (Su, Mercer, Van Hal & Maley, 2013)
LABORATORY TESTS
Test
Sensitivity Specificity Availability
Expense
Diagnostic Use
C-diff
Culture
Low
Moderate
Limited
$5-10
No diagnostic use; only
toxigenic organisms cause
disease
Toxigenic
culture
High
High
Limited
$10-30
Reference method
Epidemiologic tool
Limited diagnostic use
CCNA
High
High
Limited
$15-25
Reference Method
Limited diagnostic use
GDH
High
Low
Widely
$5-15
Diagnostically as a
screening test; must be
confirmed
Toxin EIA
Tests
Low
High
Widely
$5-15
Must detect toxins A+B;
inferior sensitivity
NAAT
High
High
Widely
$20-50
Use only in acute disease;
false positive concerns.
(Surawicz, Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)
ENVIRONMENTAL CONSIDERATIONS
 C-dif f can remain on surfaces for months or years and can be
found in multiple surfaces in the healthcare setting
 Chlorine-containing cleaning agents or other sporicidal agents
should be used to clean any equipment, beds, and rooms that
patient becomes in contact with.
 Equipment used in the care of individuals with C -dif f should
be disposable such as blood pressure cuf fs, thermometers,
stethoscopes. Other non-disposable equipment should be
cleansed with a chlorine containing solution.
(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
(Surawicz, .Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)
MANAGEMENT/ TREATMENT GUIDELINES
 Discontinue the current antimicrobial therapy as soon as possible. This
may influence the risk of CDI recurrence.
 Discontinue use of any antiperistalsis agents such as Imodium as they
my precipitate toxic megacolon.
 Probiotics use during infection is conflicting.
 If the patient is hospitalized isolation Room for Enteric Pathogen until
laborator y confirmation.
 Gown and glove for ANY per son, nur se or visitor entering the patient’s
room.
 Hand washing! Hand washing! Hand washing! No alcohol based hand
sanitizers. This is impor tant for the patient as well as nur ses, other
members of the health care team and visitors.
(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
(Surawicz, .Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)
PHARMACOLOGICAL
 Initial Treatment for Mild to Moderate Infection
 Flagyl 250 mg PO Q 6h for 10-14 days or
 Flagyl 500 mg PO Q 8h for 10-14 days
 If Symptoms persist after 5-7 days of treatment
 Vancomycin 125-500 mg PO Q 6h for 10-14 days or
 Dificid 200 mg PO BID for 10-14 days
(Kelly & LaMont, 2013), (Tannock, Munro, Taylor , Lawley, Young, Byrne, Emergy & Louie, 2010)
PHARMACOLOGICAL
 Treatment for Initial Recurrence of Mild to Moderate Infection
 New course of Flagyl for 10-14 days, may give Vanco or Dificid
 For a Second Recurrence of Mild to Moderate Infection
 Vancomycin pulse therapy: 125 – 500 mg PO Q 2-3 days for 3 weeks
 Vancomycin taper
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Week
Week
Week
Week
Week
1: 125 mg PO Q6 hours
2: 125 mg PO Q12 hours
3: 125 mg PO QD
4: 125 mg PO QOD
5 and 6: 125 mg PO Q3 days
 For Subsequent Recurrences
 Vanco or Dificid for 10-14 days follow by
 Rifaximin 200 mg PO TID x 3 days
(McFarland, Elmer & Surawicz, 2002)
PHARMACOLOGICAL
 Initial Treatment for Severe Infection
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Vanco 125 mg PO Q 6h for 10- 14 days
If no improvement of diarrhea in 3 days,
Vanco 500 mg PO Q 6h for 10-14 days
Dificid 200 mg PO BID may be substituted for Vanco if the patient
cannot tolerate Vanco
 If Critically Ill
 Vanco 500 mg PO Q 6h and Flagyl 500 mg IV Q 8h
 If toxic megacolon, ileus, or no improvement with PO meds
 Vanco Retention Enema 500 mg in 100 mL of NS Q 6h
 Continue with IV Flagyl in conjunction with retention enemas
(Kelly & LaMont, 2013), (Tannock, Munro, Taylor , Lawley, Young, Byrne, Emergy & Louie, 2010)
NON-PHARMACOLOGICAL
 Surgical Consultation Complicated CDI
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Hypotension requiring vasopressors
Sepsis and Organ dysfunction
Mental Status Changes
WBC > 50,000
Failure to improve with therapy after 5 day
 Surgical Procedures
 Subtotal Colectomy
 Diverting Loop Ileostomy with colonic lavage
 Intestinal Microbiota Transplantation (IMT)
 Otherwise known as a Fecal Transplant
(Kelly & LaMont, 2013), (Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)
INTESTINAL MICROBIOTA TRANSPLANTS
 Fecal transplants can be delivered via Nasojejunal Tube,
duodenal infusion, gastroscope, colonoscope, enema, or
rectal catheter.
 Several studies have revealed a high success rate with up to
93% success rate after 1 treatment. Cure rates after a
second infusion were 94% of remaining patients.
 Continued use of antibiotics, such as those use to treat C -Dif f
suppresses the natural flora found in the intestines.
 Eradication of C-dif f after fecal transplants is thought to occur
due to the natural flora present in stool that wards of f the C dif f infection.
(Brandt, Aroniadis, Mellow, Kanatzar, Kelly, Park, Stollman & Rohlke, 2012),(Gough, Shaikh & Manges, 2011),
(Nood, Vrieze, Nieuwdorp, Fuentes, Zoetendal, de Vos, Visser & Kuijper, 2013)
PEDIATRIC CONSIDERATIONS
 In children less than 3 years of age, testing for C -dif f is not
recommended unless the child has an accompanying
diagnosis of Hirschsprung disease or other motility disorder.
 In children who are age 3 and older who are symptomatic, a
positive test result is indicative of CDI.
 Pseudomembranous colitis seen on endoscopy is indicative of
CDI.
 Test of cure is not recommended.
 In moderate disease Flagyl 30mg/kg/day is recommended in
4 divided doses orally with a max of 2g per day.
 In severe disease Vanco 40mg/kg/day is recommended in 4
divided doses orally with a max of 2g per day
 Contact isolation with glove and gown recommended until
diarrhea has resolved.
(Committee on Infections Diseases, 2013)
FOLLOW-UP
 In non-severe cases, patient can be managed as outpatients.
 Patients should be seen 5 -7 days after the initiation of therapy
to evaluate for treatment effectiveness. If initial treatment is
not effective, alternate antibiotic should be considered.
 Due to the high rate of relapse, patients should be reevaluated
2-10 days after discontinuing antibiotics.
 In severe cases, patients will need to be admitted to the hospital
for IV antibiotic therapy and for monitoring of serum electrolytes,
treatment effectiveness, and disease complications such as toxic
megacolon, paralytic ileus, septic shock, and perforation.
 Post hospitalization patients should be again reevaluated in 1
week upon discharge and then 2 -10 days after discontinuing
antibiotic therapy for relapse.
(Domino, 2013)
COUNSELING/EDUCATION
 Good Hand Hygiene
 Encourage patients and families to use 10% bleach products
to clean their home bathrooms after each bowel movement
for two weeks.
 Use only paper towels (no cloth towels) and dispose of used
paper towels after each use.
CONSULTATION/REFERRAL
 Gastroenterologist
 Infectious Disease Specialist
 Surgical Consult
 If patients are unresponsive to initial therapy in Mild to
Moderate disease or patients who have recurrent disease,
Referral to either specialty is indicated.
TEN MULTIPLE CHOICE QUESTIONS
C-Diff is spread by
a.
b.
c.
d.
Fecal-Oral Route
Droplet
Contact
Air-borne
People can be colonized and not have any symptoms
a)
b)
True
False
Risk Factors for C-Diff include
a)
b)
c)
d)
Recent antibiotic use, recent hospitalization, age greater than 65.
Eating at a restaurant, taking antibiotics, age 25.
Upper respiratory infection, recent doctors appointment, age 40
Mild Crohn’s disease without flare up in 1 year, no healthcare in the
last 2 years, age 35.
MULTIPLE CHOICE QUESTIONS
A 56 year old male patient comes into the of fice with
complaints of watery diarrhea 3 -5 times per day and slight
cramping abdominal pain for the past 3 days. He was recently
treated in the Emergency Department with Bactrim for an
abscess but has finished the antibiotic. Blood pressure is
110/65, pulse 92, RR 18, temp 99.1 orally. What tests would
you consider for this patient?
a)
b)
c)
d)
CBC,
CBC,
CBC,
CBC,
CMP,
CMP,
CMP,
CMP,
Amylase, Lipase
CT scan
Stool Culture
Stool Culture, Stool PCR for C-diff,
MULTIPLE CHOICE QUESTIONS
What medication is recommended for treatment of mild C -dif f
in the adult.
a)
b)
c)
d)
Loperamide 4 mg PO x1 then 2 mg PO after each loose stool
Flagyl 250 mg PO Q 6 hours for 10 days
Flagyl 500 mg IV Q 6 hours
No medication is required to treat mild C -diff
What medication is can be given if a patient has moderate
C-dif f and has an allergy to Vanco.
a)
b)
c)
d)
Erythromycin
Penicillin
Dificid
Immodium
MULTIPLE CHOICE QUESTIONS
 All of the following are true except
a) Nurses need to gown and glove each time she crosses the threshold
of a patient who is suspected of having C -diff or has a positive
diagnosis of C-Diff.
b) Bleach and other sporicidals are necessary to clean all nondisposable equipment that has been utilized with a patient with C diff.
c) Patients family members who live in the same house as the patient
do not need to gown and glove when entering their family members
room because they have already been exposed.
d) C-diff can live on surfaces in the hospital environment for months.
MULTIPLE CHOICE QUESTIONS
 All children under the age of 12 months should be tested for
C-dif f because the rate of colonization is high.
a) True
b) False
 Possible complications of C -dif f include
a)
b)
c)
d)
e)
Toxic Megacolon
Dehydration
Bowel Perforation
Death
All of the above
MULTIPLE CHOICE QUESTIONS
 Treatment by which of the following has been shown to
significantly improve the recurrence of C -dif f
a.
b.
c.
d.
Colon Transplants
Continued use of clindamycin
Colon lavage
Fecal Transplants
QUESTIONS?
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