Clostridium difficile infection

Kelly Strine FNP-SNUR 652

CLOSTRIDIUM DIFFICILE

INFECTION

Clostridium diffi cile (C-diff ) is a gram-posit ive, spore-forming anaerobic baci l lus.

C-diff was init ial ly detected in 1935 in the stool of newborns and was considered nonpathogenic.

I t is spread by ingesting the spore through the fecal oral route.

Infection and colonization is usually l inked to the use of broad-spectrum antibiotic within 12 weeks, proton pump inhibitors, H2 antagonists, chemotherapy, increasing age and hospital ization.

I t is characterized by the presence of 3 or more unformed, diarrheal stools in 24 or fewer consecutive hours, a stool test result posit ive for the presence of toxigenic C-diff or its toxins, pseudomembranous colit is.

Reinfection is common and is seen in 25% of cases treated with oral antibiotics. Once a relapse has occurred, second relapse is 45%.

DEFINITION

(Lessa, Gould, and McDonald, 2012), (Kelly & LaMont, 2013)

C diffi cile colitis results from a disruption of the normal bacterial flora of the colon, ingestion of a C-Diff causing spore, colonization with C diffi cile, 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.

ETIOLOGY

(Aberra & Katz, 2013)

Colonization occurs from ingestion of C-diff 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.

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 specifi c receptors on the intestinal mucosal cells where they gain entry to the cells. The toxins produce infl ammation 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 eff ect of these toxins is what produces more severe symptoms.

PATHOPHYSIOLOGY


(Sunenshine et al, 2006)

PATHOGENESIS OF CDI

4. Toxin A & B Productionleads to colon damage +/- pseudomembrane

1. Ingestionof spores transmitted

from other patients via the hands of healthcare personnel and environment

2. Germination intogrowing (vegetative)

form

3. Altered lower intestine flora (due to antimicrobial use) allows

proliferation of C. difficile in colon

Recent hospitalizationRecent use of broad spectrum antibioticsAge greater than 65Gastrointestinal surgeryNasogastric tube feedingReduced gastric acid secretionConcurrent disease such as Inflammatory Bowel

Syndrome Impaired immunityComorbidities that cause use of additional antibiotics

RISK FACTORS

(Henrich, Krakower, Bitton & Yokoe, 2009), (Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)

The incidence of C-diff has increased across the United States, Canada and Europe. In 2008 it was reported that 8.75 per 1000 discharges in 28 southern United States community hospitals had C-diff l isted 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-diff in a survey of US health-care facil ity 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 reported each year, causing 14,000 deaths.

In the out patient setting the rate is approximately 7.7 cases per 100,000 person-years.

INCIDENCE

(Lessa, Gould & McDonald, 2012)

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

CLINICAL FINDINGS

Pseudomembranous Colitis(Aberra & Katz, 2013)(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo &

McDonald, 2013)

Possible severe disease criteria 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

DIFFERENTIATION OF DISEASE SEVERITY

(Kelly & LaMont, 2013)

Dehydration

Electrolyte Imbalances

Kidney Failure

Toxic Megacolon

Bowel Perforation

Death

COMPLICATIONS


Food poisoningEnteric infectionsAntibiotic-associated diarrheaCrohn’s DiseaseDiverticulitisViral Gastroenteritis Intra-abdominal Sepsis Irritable Bowel SyndromeMalabsorptionSalmonellosisShigellosisUlcerative ColitisVibrio Infections

DIFFERENTIAL DIAGNOSIS

(Domino, 2013)

Screening is not recommended for asymptomatic individuals

Individuals should only be tested for C-Diff if they have 3 or more watery, unformed stools per day or are have a suspected ileus due to C-diff.

SCREENING

(Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)(Surawicz, .Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)

Stool Culture for toxin-producing C-diff (*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.

LABORATORY TESTS

(Bartlett, 2010), (Belanger, Boissinot & Clairoux, 2003), (Carroll, 2011), (Humphries, Uslan & Rubin, 2012), (Su, Mercer, Van Hal & Maley, 2013)

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 methodEpidemiologic toolLimited diagnostic use

CCNA High High Limited $15-25 Reference MethodLimited 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.

LABORATORY TESTS

(Surawicz, Brandt, Binion, Ananthakrishnan, Curry, Gilligan, McFarland & Mellow, 2013)

C-diff 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-diff should be disposable such as blood pressure cuff s, thermometers, stethoscopes. Other non-disposable equipment should be cleansed with a chlorine containing solution.

ENVIRONMENTAL CONSIDERATIONS


Discontinue the current antimicrobial therapy as soon as possible. This may infl uence 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 confl icting.

If the patient is hospitalized isolation Room for Enteric Pathogen until laboratory confi rmation.

Gown and glove for ANY person, nurse or visitor entering the patient’s room.

Hand washing! Hand washing! Hand washing! No alcohol based hand sanitizers. This is important for the patient as well as nurses, other members of the health care team and visitors.

MANAGEMENT/ TREATMENT GUIDELINES


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

PHARMACOLOGICAL

(Kelly & LaMont, 2013), (Tannock, Munro, Taylor , Lawley, Young, Byrne, Emergy & Louie, 2010)

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

Week 1: 125 mg PO Q6 hours Week 2: 125 mg PO Q12 hours Week 3: 125 mg PO QD Week 4: 125 mg PO QOD Week 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

PHARMACOLOGICAL

(McFarland, Elmer & Surawicz, 2002)

Initial Treatment for Severe Infection 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

PHARMACOLOGICAL

(Kelly & LaMont, 2013), (Tannock, Munro, Taylor , Lawley, Young, Byrne, Emergy & Louie, 2010)

Surgical Consultation Complicated CDI 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

NON-PHARMACOLOGICAL

(Kelly & LaMont, 2013), (Stuart, Cohen, Dale, Gerding, Johnson, Kelly, Loo & McDonald, 2013)

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-Diff suppresses the natural fl ora found in the intestines.

Eradication of C-diff after fecal transplants is thought to occur due to the natural fl ora present in stool that wards off the C-diff infection.

INTESTINAL MICROBIOTA TRANSPLANTS

(Brandt, Aroniadis, Mellow, Kanatzar, Kelly, Park, Stollman & Rohlke, 2012),(Gough, Shaikh & Manges, 2011), (Nood, Vrieze, Nieuwdorp, Fuentes, Zoetendal, de Vos, Visser & Kuijper, 2013)

In children less than 3 years of age, testing for C-diff 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 dayContact isolation with glove and gown recommended until

diarrhea has resolved.

PEDIATRIC CONSIDERATIONS

(Committee on Infections Diseases, 2013)

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 eff ectiveness. If initial treatment is not eff ective, 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 wil l need to be admitted to the hospital for IV antibiotic therapy and for monitoring of serum electrolytes, treatment eff ectiveness, and disease complications such as toxic megacolon, paralytic i leus, 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.

FOLLOW-UP

(Domino, 2013)

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.

COUNSELING/EDUCATION

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.

CONSULTATION/REFERRAL

C-Diff is spread bya. Fecal-Oral Routeb. Dropletc. Contactd. Air-borne

People can be colonized and not have any symptomsa) Trueb) False

Risk Factors for C-Diff includec) Recent antibiotic use, recent hospitalization, age greater than 65.d) Eating at a restaurant, taking antibiotics, age 25.e) Upper respiratory infection, recent doctors appointment, age 40f) Mild Crohn’s disease without flare up in 1 year, no healthcare in

the last 2 years, age 35.

TEN MULTIPLE CHOICE QUESTIONS

A 56 year old male patient comes into the offi ce 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) CBC, CMP, Amylase, Lipaseb) CBC, CMP, CT scanc) CBC, CMP, Stool Cultured) CBC, CMP, Stool Culture, Stool PCR for C-diff,

MULTIPLE CHOICE QUESTIONS

What medication is recommended for treatment of mild C-diff in the adult.

a) Loperamide 4 mg PO x1 then 2 mg PO after each loose stoolb) Flagyl 250 mg PO Q 6 hours for 10 days c) Flagyl 500 mg IV Q 6 hoursd) No medication is required to treat mild C-diff

What medication is can be given if a patient has moderate C-diff and has an allergy to Vanco.

a) Erythromycin b) Penicillin c) Dificid d) Immodium


All of the following are true excepta) 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 non-disposable 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.


All children under the age of 12 months should be tested for C-diff because the rate of colonization is high.a) Trueb) False

Possible complications of C-diff includea) Toxic Megacolonb) Dehydrationc) Bowel Perforationd) Deathe) All of the above


Treatment by which of the following has been shown to significantly improve the recurrence of C-diffa. Colon Transplantsb. Continued use of clindamycinc. Colon lavaged. Fecal Transplants


QUESTIONS?

A b e r r a , F. N . , & K a t z , J . ( 2 0 1 3 ) . C l o s t r i d i u m d i ffi c i l e c o l i t i s . M e d s c a p e R e f e r e n c e D r u g s , D i s e a s e & P r o c e d u r e s , Re t r i e v e d f ro m h t t p : / / e m e d i c i n e . m e d s c a p e . c o m / a r t i c l e / 1 8 6 4 5 8 - o v e r v i e w

B a r t l e t t , J . G . ( 2 0 1 0 ) . Re c e n t d e v e l o p m e n t s i n t e s t i n g a n d t h e c h a n g i n g e p i d e m i o l o g y o f c l o s t r i d i u m d i ffi c i l e i n f e c t i o n . I n f e c t i o u s D i e a s e S p e c i a l E d i t i o n , 7 2 - 7 7 .

B e l a n g e r , S . D . , B o i s s i n o t , M . , & C l a i r o u x , N . ( 2 0 0 3 ) . Ra p i d d e t e c t i o n o f c l o s t r i d i u m d i ffi c i l e i n f e c e s b y re a l -t i m e p c r. J o u r n a l o f C l i n i c a l M i c r o b i o l o g y , 4 1 ( 2 ) , 7 3 0 - 7 3 4 .

B r a n d t , L . J . , A ro n i a d i s , O . C . , M e l l o w , M . , K a n a t z a r , A . , Ke l l y , C . , Pa r k , T. , S t o l l m a n , N . , & Ro h l ke , F. ( 2 0 1 2 ) . L o n g - t e r m f o l l o w - u p o f c o l o n o s c o p i c f e c a l m i c ro b i o t a t r a n s p l a n t f o r r e c u r re n t c l o s t r i d i u m d i ffi c i l e i n f e c t i o n . T h e A m e r i c a n J o u r n a l o f G a s t r o e n t e r o l o g y , 1 0 7 , 1 0 7 9 - 7 0 8 7 . d o i : 1 0 . 1 0 3 8 / a j g . 2 0 1 2 . 6 0

C a r ro l l , K . C . ( 2 0 1 1 ) . Te s t s f o r t h e d i a g n o s i s o f c l o s t r i d i u m d i ffi c i l e i n f e c t i o n : t h e n e x t g e n e r a t i o n . A n a e o r b e , 1 7 , 1 7 0 - 1 7 4 . d o i : 1 0 . 1 0 1 6 / j . a n a e ro b e . 2 0 1 1 . 0 0 2

C e n t e r s f o r D i s e a s e C o n t ro l , N a t i o n a l C e n t e r f o r E m e r g i n g a n d Z o o n o t i c I n f e c t i o u s D i s e a s e s ( N C E Z I D ) . ( 2 0 1 3 ) . C l o s t r i d i u m d i ffi c i l e i n f e c t i o n . Re t r i e v e d f ro m w e b s i t e : h t t p : / / w w w. c d c . g o v / H A I / o r g a n i s m s / c d i ff / C d i ff _ i n f e c t . h t m l

C o m m i t t e e o n I n f e c t i o n s D i s e a s e s . ( 2 0 1 3 ) . C l o s t r i d i u m d i ffi c i l e i n f e c t i o n i n i n f a n t s a n d c h i l d re n . O ffi c i a l J o u r n a l o f t h e A m e r i c a n A c a d e m y o f P e d i a t r i c s , 1 3 1 , 1 9 6 - 2 0 0 . d o i : 1 0 . 1 5 4 2 / p e d s . 2 0 1 2 - 2 9 9 2

D o m i n o , F. ( 2 0 1 3 ) . T h e fi v e m i n u t e c l i n i c a l c o n s u l t . ( 2 1 e d . ) . P h i l a d e p h i a , PA : L i p p i n c o t t W i l l i a m s & W i l k i n s . G o u g h , E . , S h a i k h , H . , & M a n g e s , A . R . ( 2 0 1 1 ) . S y s t e m a t i c r e v i e w o f i n t e s t i n a l m i c ro b i o t a t r a n s p l a t i o n ( f e c a l

b a c t e r i o t h e r a p y ) f o r r e c u r re n t c l o s t r i d i u m d i ffi c i l e i n f e c t i o n . C l i n i c a l I n f e c t i o u s D i s e a s e , 5 3 , 9 9 4 - 1 0 0 2 . d o i : 1 0 . 1 0 9 3 / c i d / c i r 6 3 2

G o u l d , C . V. , & M c D o n a l d , L . C . ( 2 0 0 8 ) . B e n c h - t o - b e d s i d e re v i e w: C l o s t r i d i u m d i ffi c i l e c o l i t i s . C r i t i c a l C a r e , 1 2 ( 1 ) , Re t r i e v e d f r o m h t t p : / / c c f o r u m . c o m / c o n t e n t / 1 2 / 1 / 2 0 3

H a m m , L . ( 2 0 0 0 ) . C l o s t r i d i u m d i ffi c i l e . P e d i a t r i c P h a r m a c o l o g y , 6 ( 6 ) , H e n r i c h , T. J . , K r a ko w e r , D . , B i t t o n , A . , & Yo ko e , D . S . ( 2 0 0 9 ) . C l i n i c a l r i s k f a c t o r s f o r s e v e re c l o s t r i d i u m

d i ffi c i l e - a s s o c i a t e d d i s e a s e . E m e r g i n g I n f e c t i o n D i s e a s e s , 1 5 ( 3 ) , 4 1 5 - 4 2 1 . d o i : 1 0 . 3 2 0 1 / e i d 1 5 0 3 . 0 8 0 3 1 2 H u m p h r i e s , R . M . , U s l a n , D . Z . , & Ru b i n , Z . ( 2 0 1 2 ) . Pe r f o r m a n c e o f c l o s t r i d i u m d i ffi c i l e t ox i n e n z y m e

i m m u n o a s s a y a n d n u c l e i c a c i d a m p l i fi c a t i o n t e s t s s t r a t i fi e d b y p a t i e n t d i s e a s e s e v e r i t y. J o u r n a l o f C l i n i c a l M i c r o b i o l o g y , 5 1 ( 3 ) , 8 6 9 - 8 7 3 q 1 0 . 1 1 2 8 / J C M . 0 2 9 7 0 - 1 2 .

J o h n s t o n , B . C . , M a , S . Y. , G o l d e n b e r g , J . Z . , T h o r l u n d , K . , Va n d v i k , P. O. , L o e b , M . , & G u y a t t , G . H . ( 2 0 1 2 ) . P ro b i o t i c s f o r t h e p re v e n t i o n o f c l o s t r i d i u m d i ffi c i l e - a s s o c i a t e d d i a r r h e a . A n n a l s o f I n t e r n a l M e d i c i n e , 1 5 7 , 8 7 8 - 8 8 8 .

Ke l l y , C . P. , & L a M o n t , J . T. ( 2 0 1 3 ) . C l o s t r i d i u m d i ffi c i l e i n a d u l t s : Tre a t m e n t . U p To D a t e ,

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S t u a r t , H . , C o h e n , M . D . , D a l e , N . , G e rd i n g , M . D . , J o h n s o n , S . , Ke l l y , C . P. , L o o , V. G . , & M c D o n a l d , L . C . ( 2 0 1 3 ) . C l i n i c a l p r a c t i c e g u i d e l i n e s f o r c l o s t r i d i u m d i ffi c i l e i n f e c t i o n s i n a d u l t s : 2 0 1 0 u p d a t e b y t h e s o c i e t y f o r h e a l t h c a re e p i d e m i o l o g y o f a m e r i c a n a n d t h e i n f e c t i o n d i s e a s e s s o c i e t y o f a m e r i c a . I n f e c t i o n C o n t ro l a n d H o s p i t a l E p i d e m i o l o g y , 3 1 ( 5 ) , 4 3 1 - 4 5 5 .

S u r a w i c z , C . M . , . B r a n d t , L . J . , B i n i o n , D . G . , A n a n t h a k r i s h n a n , A . N . , C u r r y , S . R . , G i l l i g a n , P. H . , M c Fa r l a n d , L . V. , & M e l l o w , M . ( 2 0 1 3 ) . G u i l d e l i n e s f o r d i a g n o s i s , t r e a t m e n t , a n d p re v e n t i o n o f c l o s t r i d i u m d i ffi c i l e i n f e c t i o n s . T h e A m e r i c a n J o u rn a l o f G a s t ro e n t e ro l o g y , 1 0 8 , 4 7 8 - 7 9 8 . d o i : 1 0 . 1 0 3 8 / a j g . 2 0 1 3 . 4

S u , W. Y. , M e rc e r , J . , Va n H a l , S . J . , & M a l e y , M . ( 2 0 1 3 ) . C l o s t r i d i u m d i ffi c i l e t e s t i n g : H a v e w e g o t i t r i g h t ? . J o u rn a l o f C l i n i c a l M i c ro b i o l o g y , 5 1 ( 1 ) , 3 7 7 - 3 7 8 . d o i : 1 0 . 1 1 2 8 / J C M . 0 2 1 8 9 - 1 2

Ta n n o c k , G . W. , M u n ro , K . , Ta y l o r , C . , L a w l e y , B . , Yo u n g , W. , B y rn e , B . , E m e rg y , J . , & L o u i e , T. ( 2 0 1 0 ) . A n e w m a c ro c y c l i c a n t i b i o t i c , fi d a xo m i c i n ( o p t - 8 0 ) , c a u s e s l e s s a l t e r a t i o n t o t h e b o w e l m i c ro b i o t a o f c l o s t r i d i u m d i ffi c i l e - i n f e c t e d p a t i e n t s t h a n d o e s v a n c o m y c i n . S o c i e t y o f G e n e r a l M i c ro b i o l o g y J o u rn a l s , 1 5 6 , 3 3 5 4 - 3 3 5 9 . d o i : 1 0 . 1 0 9 9 / m i c . 0 . 0 4 2 0 1 0 - 0

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