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CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
Index:
Indications for CDI testing…………………………….
Bristol Stool Chart……………………………………..
Diagnostic and Treatment Algorithm………………….
Assay Results and Interpretation………………………
Infection Prevention Measures………………………...
Tables of Disease Severity and Treatment.……………
Chemoprophylaxis for Recurrent CDI………………...
Outpatient Oral Vancomycin Therapy Guide…………
Page 1
Page 2
Page 3
Page 4
Page 4
Page 5
Page 6
Page 7
INDICATIONS FOR TESTING:

On admission: Patients with diarrhea whose differential diagnosis includes:
o Community-onset CDI
o Healthcare-facility associated CDI in recently hospitalized patients, nursing home
residents, frequent outpatient exposure to healthcare settings such as dialysis,
appointments, etc.

Hospitalized patients: New onset of clinically significant diarrhea
o Defined as 3 or more diarrheal bowel movements (Type 6 or 7 on Bristol Stool
Chart, see page 2) in 24 hours OR a patient self-report of new onset of loose
stools and abdominal pain
o Significant deviation from baseline stooling pattern in patients with ostomy, tube
feeds, or other causes of chronically loose/high output stools
Additional factors to consider:
 new unexplained fever/leukocytosis in a hospitalized patient
 age > 60 years
 recent history of antibiotic exposure
 history of gastrointestinal surgery or irritable bowel disease (IBD)
 co-existing immunodeficiency (i.e. HIV/AIDS, recent chemotherapy)
 multiple comorbidities
 indicators of potential disease severity
o age > 60 years, temperature > 38.3°C, albumin < 2.5 mg/dL, peripheral WBC count ≥ 15,000
cells/mm3, acute renal failure (> 1.5 x baseline)
 a high clinical suspicion for CDI and high clinical acuity should prompt testing as
soon as possible
Situations when testing is not advised:
 negative C. difficile stool assay in the last 72 hours
 diarrhea in the setting of a laxative or a bowel stimulant in the previous 48 hours
 test of cure
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
1
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
2
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
Clinical Suspicion of CDI






Order one C. difficile stool assay
Discontinue antidiarrheals, antiperistaltics, and unnecessary antibiotics
Reevaluate necessity of acid suppressive medications
Maintain hydration and electrolyte replacement
Consider empiric C. difficile treatment
Implement empiric contact isolation if expected testing turnaround time > 4hours
GDH antigen (+); toxin A/B (+)
GDH antigen (-); toxin A/B (+)
GDH antigen (+); toxin A/B (-)
 PCR testing done
PCR (+)
PCR (-)
No Clostridium difficile Infection:
Clostridium difficile Infection:







Confirm that patient is in contact isolation
Continue contact isolation until resolution of
symptoms and end of therapy (see page 4)
Begin CDI treatment (see page 5)
Consult Infectious Diseases and/or G.I. for
diagnostic uncertainty
Consult Surgery for Severe CDI
Signs and symptoms improve in
4-6 days:
 Complete course of therapy
 Further stool testing is not
advised
 Room is terminally cleaned
GDH antigen (-); toxin A/B (-)


Discontinue CDI treatment if initiated
Discontinue empiric contact precautions for
CDI if initiated
Evaluate other causes of diarrhea if
appropriate
May repeat C difficile stool assay after 72
hours in patients with persistent diarrhea
No improvement of diarrhea
within 4-6 days and patient
receiving oral metronidazole:
 Start oral vancomycin
 Consider IV metronidazole
(see page 5)
Progressive signs and
symptoms (toxic megacolon,
fulminant colitis):
 Obtain abdominal/pelvic
CT scan
 Begin therapy for severe or
fulminant disease (page 5)
 Consult Surgery
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
3
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
.
CLOSTRIDIUM DIFFICILE ASSAY RESULTS AND INTERPRETATION
GDH Result
Toxin Assay Result
Interpretation
Recommendations
Negative
Negative
No CDI present
No further action. Repeat testing is
discouraged. Discontinue contact
isolation as appropriate.
Discrepant GDH and Toxin results
Reflex to PCR by Microbiology Lab
Positive
Positive
If PCR is Negative:
No CDI present
If PCR is Positive:
CDI is present
CDI is present
Continue contact isolation and begin
therapy. Repeat testing is
discouraged.

C. difficile GDH/Toxin EIA Performance Characteristics
Sensitivity 90.5%, Specificity 93.1%, PPV 76.4%, NPV 97.6%

C. difficile PCR Assay Performance Characteristics
Sensitivity 98.8%, Specificity 90.9%, PPV 56%, NPV 99.8%
INFECTION PREVENTION MEASURES



All patient care units will use the same procedures for testing, treatment, and isolation.
All patients with presumed or suspected C. difficile should be isolated if CDI testing is
expected to take > 4 hours to result back to provider.
Isolation procedures include: use of dedicated patient equipment, universal glove and gown
use, hand hygiene with alcohol based sanitizer before and after entry and exit of patient
room, followed by hand washing with soap and water after room exit if a sink is readily
available.
o The patient is cleared of the need for isolation once treatment is completed and
the patient is asymptomatic (stools back to baseline consistency), and if the flag is
removed by the Infection Prevention Program.
o Terminal cleaning of rooms of all patients with C. difficile infection must occur
once the isolation status is discontinued or the patient is discharged. Rooms that
housed patients with C. difficile must be cleared with the ATP Bioluminescence
assay by Environmental Services, and may require terminal disinfection with UV.
Contact Infection Prevention and Environmental Services for assistance.
o Please refer to the RGHS Infection Prevention Manual for further guidance on
isolation precautions in CDI.
http://rghsportal/Policies/2012r5%20IP%20Manual%20REVISED%20(8).pdf
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
4
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
DISEASE SEVERITY AND TREATMENT RECOMMENDATIONS:
General note: for CDI patients requiring continued broad-spectrum antimicrobial therapy, consideration
should be given to continuing CDI treatment for the duration of concomitant antimicrobials, or evaluating
for secondary CDI prophylaxis (page 6)
Mild to Moderate CDI: minimal evidence of toxicity
Assessment
Drug of choice
Initial episode
Metronidazole 500 mg PO q8 for 10-14 days
Recurrent episode
 Metronidazole 500 mg PO q8 for 10 – 14 days
OR
 Vancomycin 125mg PO q6 for 10 – 14 days
 Consider an oral vancomycin taper after
completion of therapy in patients with
multiple recurrences:
• Week 1: Vancomycin 125 mg PO q12h
• Week 2: Vancomycin 125 mg PO q24h
• Week 3: Vancomycin 125 mg PO q48h
• Week 4: Vancomycin 125 mg PO q72h
Comment
If no clinical improvement in 4-6
days, consider changing to oral
vancomycin for severe CDI.
1st recurrence: Retreatment with
metronidazole is preferable for
mild-moderate CDI.
> 1 recurrence: Treatment
requires oral vancomycin.
If recurrence is severe or
fulminant, see below.
Severe CDI: any of the following criteria
 endoscopic evidence of pseudomembranous colitis
● requires treatment for C. difficile in the ICU
 at least 2 of the following not attributable to other causes: age > 60 years, temperature > 38.3°C, albumin < 2.5
mg/dL, peripheral WBC count ≥ 15,000 cells/mm3, acute renal failure (> 1.5 x baseline)
Assessment
Initial episode
Severe CDI
developing despite
therapy for mild to
moderate CDI
Drug of choice
Vancomycin 125 mg PO q6 for 10-14 days
Severe,
complicated CDI
Vancomycin 500 mg PO q6 for 10-14 days
Vancomycin 125 mg PO q6 for 10-14 days
± Metronidazole 500 mg IV q8
Comment
Please Note: There is no literature
suggesting combination oral
metronidazole and oral
vancomycin offers clinical benefit
over oral vancomycin alone.
Evaluate for fulminant CDI and
treat accordingly.
Consider adding Metronidazole 500 mg IV q8* if Encourage Surgical/Infectious
ileus or otherwise unable to ascertain adequate
Diseases and/or GI consult.
bioavailability of oral agents
Fulminant CDI: evidence of ileus, toxic megacolon, hypotension or shock, or colonic perforation
Assessment
Drug of choice
Comment
Urgent Surgery consult
Initial CDI episode Vancomycin 500 mg PO q6 for 10 – 14 days
or worsening
PLUS
Strongly encourage Infectious
despite therapy
Metronidazole 500 mg IV q8* for 10 – 14 days
Ileus present
Consider adding per rectum Vancomycin 500 mg Diseases and/or GI consult
in 500 mL of 0.9% NaCl q4-12 hours
* Note: IV metronidazole may be discontinued when clinically stable and ileus resolved .
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
5
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
CHEMOPROPHYLAXIS OF RECURRENT CDI

Primary Prophylaxis:
o Current literature does not support primary prophylaxis for high risk patients who
have never had CDI

Secondary Prophylaxis:
o Patients with recent or prior CDI requiring antimicrobial therapy for another
indication may be at risk of CDI recurrence.
o Routine use of secondary CDI prophylaxis in such cases has not been
evaluated in the literature, may place the patient at risk for unnecessary
drug related toxicities, and may promote emergence of drug-resistant
organisms such as vancomycin-resistant enterococci (VRE).
o The risks and benefits of CDI prophylaxis should be considered for each clinical
scenario. The following is an effort to provide guidance to prescribing physicians
who choose to implement CDI secondary prophylaxis for certain high risk
patients on a case-by-case basis. Contact ASP for guidance if secondary
prophylaxis of CDI is initiated for any patient.
o Patients who may benefit from CDI secondary prophylaxis:
 A history of documented recurrent CDI (> 2 episodes), most recent
episode treated with symptom resolution within the preceding 3 months
 A history of severe, life-threatening CDI at any time in the past
o Recommended therapy
 Vancomycin 125 mg PO q24h
o Duration of prophylaxis
 Prophylaxis can be given for the duration of concomitant antimicrobial
therapy, plus 7 days beyond completion of the other antimicrobials.
 Alternatively, consideration may be given to tapering doses of oral
vancomycin (q24h, q48, q72h) over 2-3 weeks upon completion of other
antimicrobials.
References:
Cohen S et al. Infection Control and Hospital Epidemiology 2010; 31:5
Zar F et al. Clinical Infectious Diseases 2007; 45: 302
Katz, DA et al Americal Journal of Medicine 1996; 100
Patterson LR et al Annals of Internal Medicine 2009; 151
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
6
CLINICAL TREATMENT GUIDELINES FOR
CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS
OUTPATIENT ORAL VANCOMYCIN THERAPY
Pharmacotherapy with oral vancomycin products for the treatment of Clostridium difficile infections in
adults is extremely costly (see table below). In an attempt to help reduce medication expenses, some
retail pharmacies readily compound oral vancomycin solution from the commercially available
vancomycin powder for injection. Please consider providing this information to your patients if oral
vancomycin therapy is warranted. Other neighborhood pharmacies may be capable of compounding oral
vancomycin solution; however, it is recommended to call in advance if the below pharmacies are not a
feasible option.
Product
Drug Acquisition Costs*
Vancomycin Oral Capsule – 125 mg
Vancomycin Oral Capsule – 250 mg
Vancomycin Oral Capsule – 500 mg
Vancomycin Powder for Injection – 1 gram
(powder used to compound solution)
Vancomycin Powder for Injection – 5 grams
(powder used to compound solution)
Vancomycin Powder for Injection – 10 grams
(powder used to compound solution)
$23.54/capsule
$43.40/capsule
$86.80/2 capsules
$4.25/vial
$24.28/vial
$35.79/vial
Total Cost of Therapy*
(14 Days)
$1318.24
$2430.40
$4860.80
$119 (maximum
recommended dose)
$ 135.97 (maximum
recommended dose)
$107.37 (maximum
recommended dose)
* Total Cost of Therapy based on 2010 drug acquisition costs at RGH
Oral Vancomycin Solution Concentration: 250 mg/5 mL
Readily Available Compounding Pharmacies in Rochester, NY and Surrounding Areas:
The General Apothecary
Rochester General Hospital
1415 Portland Ave, Suite 125
Rochester, NY 14621
(585) 922-3970
RMH Retail Pharmacy LLC
1500 N James St
Rome, NY 13440
(315) 338-7690
Twelve Corners Apothecary
1832 Monroe Avenue
Rochester, NY 14618
(585) 244-8600
Pine Pharmacy
5110 Main St, Suite 101
Williamsville, NY 14221
(716) 332-2288
R Drugs Etc
222 Alexander Street, #2700
Rochester, NY 14607
(5850 262-3760
Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D.
Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention
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