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Clostridium difficile Infection: Prevention, Diagnosis and Treatment – Adult/Pediatric – Inpatient/Ambulatory/Emergency Department

Clostridium difficile Infection: Prevention, Diagnosis and Treatment – Adult/Pediatric – Inpatient/Ambulatory/Emergency Department - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Infection and Isolation


1
Clostridium difficile Infection: Prevention,
Diagnosis and Treatment – Adult/Pediatric –
Inpatient/Ambulatory/Emergency Department
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................................................... 3
SCOPE .................................................................................................................................................................... 4
METHODOLOGY ..................................................................................................................................................... 5
INTRODUCTION ..................................................................................................................................................... 6
RECOMMENDATIONS ............................................................................................................................................ 7
DISEASE PREVENTION...................................................................................................................................................... 7
Probiotics for disease prevention .......................................................................................................................... 7
Infection Control for hospital admission with C Diff Diagnosis ............................................................................. 7
Infection control in the ambulatory clinic ............................................................................................................. 9
Infection control at home ...................................................................................................................................... 9
DIAGNOSIS .................................................................................................................................................................. 10
Clinical Characteristics and Risk Factors ............................................................................................................. 10
DIAGNOSTIC TESTING .................................................................................................................................................... 10
ANTIMICROBIAL TREATMENT OF INITIAL INFECTION ............................................................................................................. 12
Relapse Prevention in Adult Patients .................................................................................................................. 15
ANTIMICROBIAL TREATMENT OF RELAPSE/RECURRENT INFECTION ......................................................................................... 16
Fidaxomicin ......................................................................................................................................................... 17
NON-ANTIMICROBIAL INTERVENTIONS FOR RECURRENT INFECTION........................................................................................ 18
Intravenous Immune Globulin (IVIG) ................................................................................................................... 18
Bezlotoxumab ..................................................................................................................................................... 19
Fecal microbiota therapy (FMT) .......................................................................................................................... 19
UW HEALTH IMPLEMENTATION ........................................................................................................................... 20
APPENDIX A. EVIDENCE GRADING SCHEME(S) ..................................................................................................... 22
APPENDIX B. ADULT INPATIENT PCT TESTING ALGORITHM FOR CDI .................................................................... 23
APPENDIX C. PEDIATRIC INPATIENT PCR TESTING ALGORITHM FOR CDI .............................................................. 24
APPENDIX D. ADULT TREATMENT PATHWAY ALGORITHM FOR CDI ..................................................................... 25
APPENDIX E. PEDIATRIC TREATMENT ALGORITHM FOR CDI................................................................................. 26
REFERENCES ......................................................................................................................................................... 27
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
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2


Contact for Content:
Name: Nasia Safdar, MD, PhD- Infectious Disease
Phone Number: (608) 213-4075
Email Address: ns2@medicine.wisc.edu

Name: Sheryl Henderson, MD, PhD- Pediatric Infectious Disease
Phone Number: (608) 265-6488
Email Address: shenderson@pediatrics.wisc.edu

Contact for Changes:
Name: Katherine Le, PharmD - Center for Clinical Knowledge Management (CCKM)
Phone Number: (608) 890-5898
Email Address: kle@uwhealth.org

Coordinating Team Members:
Patti Anderson- Laboratory
Jessica Branson- Oncology Services
Derrick Chen, MD- Pathology
Barry Fox, MD- Infectious Disease
Jennifer Hankwitz- Trauma Life Support
Sheryl Henderson, MD- Pediatric Infectious Disease
Lalitha Iyer, MD- General Pediatrics
David Kiefer, MD- Family Medicine
Anne Leclaire-Thoma MSN, RN, CRRN- Nursing Quality and Safety
Lauren Legenza, PharmD- Pharmacy Fellow
Mark Micek, MD- Internal Medicine
Michael Pulia, MD- Emergency Medicine
Lucas Schulz, PharmD- Pharmacy- Inpatient
Kristan Sodergren, NP- Pediatric Hospital Medicine
Linda Stevens, DNP, RN-BC, CPHQ, CSPHP- Nursing Quality and Safety
Josh Vanderloo, PharmD- Drug Policy Program
Beth Weiler- Environmental Services
Marc-Oliver Wright MT, MS, CIC, FAPIC- Infection Control


Committee Approvals/Dates:
Clinical Knowledge Management (CKM) Council (08/24/2017)


Release Date: August 2017 | Next Review Date: May 2019










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3


Executive Summary
Guideline Overview
This guideline contains recommendations for the prevention, diagnosis, management, and
treatment of Clostridium difficile infection (CDI) in pediatric and adult patients, and is heavily
influenced by documents released by the Society of Healthcare Epidemiology of America
(SHEA) and the Infectious Diseases Society of America (IDSA) and the American Academy of
Pediatric (AAP).

Key Revisions (2017 Periodic Review)
1. The following tables were added to the guideline: Low/High risk antibiotics potential for C.
Diff infection, Enhanced contact precautions measures for patients with CDI, Risk factors for
first infection with Clostridium difficile in adults with diarrhea, When to test for C diff Infection,
and Criteria to consider for Moderate to Severe CDI in adults.
2. New recommendations for hospital area restrictions for symptomatic patients, infection
control in the ambulatory clinic and infection control at home.
3. New adult and pediatric C. Diff treatment algorithms.
4. Revised text for low-dose vancomycin use for CDI relapse prevention in adults.
5. New recommendation for inpatient use of bezlotoxumab for CDI preventive therapy.

Key Practice Recommendations
Prevention
1. Compliance with UW Health enhanced contact precautions for patients with onset of
diarrhea or with suspected CDI should be immediately implemented. Clostridium difficile
isolation precautions should remain in place for the duration of hospitalization or 90 days
from the last positive test (whichever is longer).
2. Hand washing with soap and water upon exit and barrier precautions, including gloves and
gowns, should be used upon entry by all health-care workers, patients, and visitors within
the room of any patient with known or suspected CDI.
3. Single patient-use disposable equipment should be used for prevention of Clostridium
difficile transmission. Non-disposable medical equipment should be dedicated to the
patient’s room and other equipment should be thoroughly cleaned with an approved
sporicidal agent, as appropriate, after use in patients with CDI.
4. Education should be provided to the patient and family related to Clostridium difficile risk
during antibiotic therapy.
5. The use of proton pump inhibitors should be minimized, if possible, as the duration of PPI
therapy has been associated with CDI in adult patients. Switching to H
2
blockers may be
considered, if stopping therapy all together cannot be achieved.
6. Probiotics may be considered for primary prevention of CDI in immunocompetent adults
prescribed an antibiotic course with a high risk antibiotic, and should be considered for
patients who are otherwise at risk of CDI. The preferred probiotic at UW Health is
Lactobacillus GG.
7. Prophylaxis with metronidazole or vancomycin may be considered in patients with a recent
diagnosis of CDI that require subsequent broad spectrum antibiotic therapy.
8. For patients remaining on therapeutic antibiotics, consideration should be given to
continuing ‘dose reduced’ (i.e., vancomycin 125 mg PO BID or metronidazole 500 mg PO
once daily or BID) through the course of therapy and for 5 days following completion.




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4


Diagnosis
1. Patients > 3 years of age experiencing diarrhea (≥ 3 unformed stools in the previous 24
hours) without an alternative etiology and at-risk for CDI should be evaluated for the
presence of Clostridium difficile.
2. Testing of patients younger than one year of age is discouraged due to high colonization
rates in asymptomatic patients. Testing of children age 12-36 months should only be
considered in the setting of appropriate risk factors and with evaluation of other potential
etiologies.
3. Evaluation of patients without diarrhea or risk factors should be avoided. Routine screening
for Clostridium difficile in patients without diarrhea is not recommended and asymptomatic
carriers should not be treated.
4. Testing for Clostridium difficile should be performed on diarrheal (unformed) stool
specimens, unless ileus due to Clostridium difficile is suspected.
5. Polymerase chain reaction (PCR) testing of stool samples for toxigenic Clostridium difficile is
preferred for standard diagnostic testing. Repeat testing for Clostridium difficile by PCR is
not recommended and testing for cure should not routinely be performed.

Treatment
1. The most important treatment for Clostridium difficile is prevention.
2. Discontinue therapy or deescalate spectrum with inciting antimicrobial agent(s) as soon as
possible, when feasible.
3. Initiate treatment with first choice therapeutic options metronidazole and/or vancomycin.
Duration of therapy should generally not exceed 14 days, except when concomitant
antibiotics need to be administered in which case treatment may be extended for 5 days
after finishing the concomitant antibiotic.
4. Anti-peristaltic agents should be avoided in patients with suspected or confirmed CDI as
they may obscure symptoms of infection.
5. Low-dose metronidazole (500 mg PO once or twice daily) or low-dose vancomycin (125 mg
orally twice daily) may be considered in patients who have a history of CDI and are being
treated with antibiotics for a non-CDI infection.
6. Fidaxomicin is usually reserved for adult patients that relapse or have recurrence after
treatment with metronidazole and vancomycin, and in adult patients with low levels of
neutralizing antibodies to Clostridium difficile.
7. Fecal microbiota therapy (FMT) is an acute treatment for relapsing disease and may be
considered under unique circumstances. For adults and pediatric patients, it should be
done in consultation with Infectious Disease and Gastroenterology services and with the
Pediatric Infectious Diseases and Pediatric Gastroenterology services respectively.
Scope
Disease/Condition(s): Clostridium difficile infection (CDI)

Clinical Specialty: Infectious Disease/Control, Gastroenterology, Preventive Medicine, Primary
Care, Emergency Medicine, All Inpatient Services, Pediatric Infectious Disease, Pediatric
Gastroenterology
Intended Users: Physicians, Nurses, Advanced Practice Providers, Pharmacists,
Environmental Services staff

Objective(s): To provide recommendations for the diagnosis and management of patients with
CDI. The guideline also contains guidance for prevention of CDI and infection control within the
inpatient and ambulatory settings.
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5



Target Population: Pediatric and adult patients at risk for or diagnosed with Clostridium difficile
infection.

Interventions and Practices Considered:
Diagnosis
• Testing of stool for Clostridium difficile via polymerase change reaction (PCR)
(preferred) or by cytotoxin assay
• Computer tomography (CT) scanning of the abdomen and pelvis in severe cases

Management/Treatment
• Antimicrobial use restriction
• Avoidance of antiperistaltic agents
• Initiate treatment including metronidazole, vancomycin, and/or fidaxomicin
• Surgical consultation
• Fecal microbiota therapy

Prevention
• Hospital-based infection control programs
• Antibiotic use restrictions
• Enhanced Contact Precautions
• Use of private rooms, when applicable
• Hand hygiene and barrier precautions
• Disinfection of environmental surfaces with sporicidal agents

Major Outcomes Considered:
• Sensitivity and specificity of diagnostic testing
• Rates of CDI
• Morbidity/Mortality
• Number of cases of severe disease nosocomially acquired and requiring surgical
intervention
• Length of hospital stay
• Rates of relapse in hospital or requiring hospital readmission within 60 days of hospital
associated CDI episode
• Xenex UV light disinfection use on high risk units and where use is available

Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline author(s) and
workgroup members to collect evidence for review. Expert opinion and clinical experience were
also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external
organizations and/or arrived at a consensus through discussion of the literature and expert
experience. All recommendations endorsed or developed by the guideline workgroup were
reviewed and approved by other stakeholders or committees (as appropriate).

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
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Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Recommendations developed by external organizations maintained the evidence grade
assigned within the original source document and were adopted for use at UW Health.

Internally developed recommendations, or those adopted from external sources without an
assigned evidence grade, were evaluated by the guideline workgroup using an algorithm
adapted from the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) methodology (see Figure 1 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme(s) used within this document.

Recognition of Potential Health Care Disparities: Clostridium difficile is the most common
cause of infectious diarrhea in hospitalized patients in high-income countries like the United
States.
1

Introduction
Clostridium difficile infection (CDI) is the most frequent cause of health care-associated diarrhea
and is now the most common hospital-acquired infection.
2-5
Because of the increasing
incidence, severity, and costs associated with CDI, there is a substantial need to prevent
exposure and transmission of CDI, as well as to improve the treatment of patients with CDI.
6


Clostridium difficile is a spore forming, anaerobic, gram positive, bacilli responsible for 15-25%
of cases of nosocomial diarrhea and 20-30% of antibiotic associated diarrhea in adult patients.
Toxigenic species are capable of producing toxin A, toxin B, a binary toxin, or a combination.
Clostridium difficile infection can manifest from symptomless carriage and minor diarrhea to fatal
pseudomembranous colitis and toxic megacolon, sepsis, bowel perforation and death.
4,7

Mortality rates from CDI increased from 5.7 per million population in 1999 to 23.7 per million in
2004.
8
It is projected to nationally cause $3.2 billion in health care costs.

In recent years a particularly virulent strain of Clostridium difficile, BI/NAP1, has become a major
pathogen in the development of CDI. BI/NAP1 has increased virulence characteristics
including: increased toxin production, binary toxin, hyper-sporulation, and resistance to
fluoroquinolone antibiotics.
4,7
Recurrence of CDI is highest in the 7-14 days after completion of
initial therapy, but persists for up to 90 days. The risk of recurrence increases as the number of
infections or reinfections increase.
4,7


Studies in pediatrics have also shown an increase in the prevalence of hospital acquired and
community acquired C. difficile in recent years.
9-11
However, unlike in the adult population, the
prevalence remains low, and the clinical symptomatology is less severe. Community acquired
infections account for ~70% of cases.
10,11
The diagnosis of CDI in young children and infants
remains challenging in the setting of low prevalence rates of infection and high rates of
asymptomatic carriage in this population.
12
Numerous studies have demonstrated high
colonization rates (30-70%) of both toxigenic and non-toxigenic C. difficile in asymptomatic
infants younger than 12 months.
12-14
This asymptomatic colonization rate has been shown to
decrease as children over the next two years. By age 3, the rate is is < 3%, similar to that in
adults.
13,14

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
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7


Recommendations
Disease Prevention
Probiotics for disease prevention
Due to the lack of controlled clinical trials, probiotics are not currently recommended by the
American Academy of Pediatrics for primary prevention of CDI in pediatric patients.
14-16
(UW
Health Very low quality of evidence, strong recommendation) However, it t is reasonable to consider
prescribing probiotics for the primary prevention of CDI in most immunocompetent adult patients
receiving therapeutic, antibiotic therapies.
17,18
(UW Health Class Low quality of evidence, strong
recommendation) Adult patients prescribed high-risk antibiotics or who exhibit additional risk
factors, including the use of two or more antibiotic therapies (see Risk Factors), should be
considered for probiotic therapy.
17,18
(UW Health Moderate quality of evidence, strong
recommendation) The most common adverse events experienced by patients on probiotics
included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbances.
17,18

No specific probiotic formation has shown superior results; therefore the preferred probiotic at
UW Health is Lactobacillus GG.
19


Table 1. Low/High-risk antibiotics potential for C. Diff infection
5

Low risk antibiotics High risk antibiotics
• Aminoglycosides
• Macrolides (e.g., azithromycin)
• Trimethoprim/sulfamethoxazole*
prophylaxis or treatment duration less
than 5 days
• Tetracyclines
• Daptomycin
• Aztreonam
• Fluoroquinolones
• 1
st
-4
th
generation cephalosporins
• Beta-lactamase inhibitor combinations
• Sulfmonamides or
Trimethoprim/sulfamethoxazole*
• Clindamycin
• Carbapenems
• Vancomycin
• ≥ 2 antibiotics of any risk
* “Low risk” trimethoprim/sulfamethoxazole use is considered prophylaxis or treatment duration
less than 5 days. “High risk” sulfonamide or trimethoprim/sulfamethoxazole use is considered
dosing ≥ 10mg/kg/day AND duration ≥ 7 days.

Infection Control for hospital admission with C Diff Diagnosis
A hospital-based infection control program in conjunction with a hospital antimicrobial
stewardship program can help to decrease the incidence of CDI.
4,20,21
(SHEA-IDSA Evidence
Grade A, Category II)

Appropriate antibiotic utilization
It is recommended that prescribers be educated to minimize the use of antibiotics, especially
high risk (see Table 1.) (SHEA-IDSA Evidence Grade A, Category II) such as broad spectrum
cephalosporins, clindamycin, and fluoroquinolones.
3,4
(SHEA-IDSA Evidence Grade C, Category III)

Ulcer protection therapy/Proton pump inhibitors
Use of proton pump inhibitors (PPI) should be minimized as duration of PPI therapy has been
associated with CDI in adults.
22
(UW Health Low quality of evidence, strong recommendation)
Switching to H
2
blockers may be considered, if stopping therapy all together cannot be
achieved.
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8



Patient room placement and contact precautions
Inpatients with known or suspected CDI should be placed in a private room (preferred) or in a
room with another patient with documented CDI.
4,14,21,23
(SHEA-IDSA Evidence Grade B, Category
III) Isolation of patients should not wait until a positive Clostridium difficile test is returned. (UW
Health Moderate quality of evidence, strong recommendation) Enhanced contact precautions should
be initiated and maintained for the duration of hospitalization or 90 days from the last positive
test (whichever is longer). Patients readmitted to the hospital within 90 days should also be
placed in contact isolation and re-evaluated by Infection Control.

Barrier precautions, including gloves (SHEA-IDSA Evidence Grade A, Category I) and gowns
(SHEA-IDSA Evidence Grade B, Category III), should be used by all health-care workers and
visitors upon entry to the room of any patient with known or suspected CDI. Hand washing with
soap and water upon leaving the room should be used by all health-care workers, patients, and
visitors upon exiting the room of any patient with known or suspected CDI.
4,14,21,23-25
Alcohol
hand rub or sanitizer alone is not sufficient in disinfecting or removing Clostridium difficile
spores.
24


Single-use disposable equipment, including stethoscopes, should be used for prevention of CDI
transmission. Equipment that is not disposable should be thoroughly cleaned with a sporicidal
agent after use in a patient with CDI.
4,14,23,25,26
(UW Health High quality of evidence, strong
recommendation) UW Health Environmental Services should utilize sporicidal agents for daily
cleaning and cleaning at discharge of the isolation room(s), in order to effectively kill Clostridium
difficile spores on surfaces.
4,23
(SHEA-IDSA Evidence Grade B, Category II) Ultraviolet (UV) light
disinfection at discharge may also be undertaken to reduce environmental burden of Clostridium
difficile. (UW Health Low quality of evidence, weak/conditional recommendation) Table 2 summarizes
key contact precaution measures clinicians and staff should adhere to with patients who have
CDI.

Table 2. Enhanced contact precautions measures for patients with CDI
Hospital Precautions Staff specific precautions
• Rooming – patient placed in private room
or with another patient with documented
CDI infection
• Signage – contact precautions posted on
door, alcohol dispenser in/or assigned
room covering dispense
• Duration - Contact precautions should be
initiated/maintained for entirety of
admission or 90 days from the last positive
test (whichever is longer). Patients
readmitted to the hospital within 90 days
should also be placed in contact isolation,
and patients awaiting fecal microbiota
transplant (FMT)
• Accessibility – Personal protective
equipment (PPE) should stocked and
available in necessary sizes; room sink
should be easily accessible for washing
hands
• Hand hygiene before gloves – Use
alcohol gel or soap and water prior to
wearing gloves
• Wash with soap and water before
exiting– wash hands with soap and water
after patient encounter
• Disposable equipment – When possible,
disposable equipment (including
stethoscopes) should be used; otherwise
all equipment must be cleaned with
sporicidal agent
• PPE wearing – Put on gowns and gloves
prior to entering room and gown should be
tied; PPE may be disposed in room once
patient interaction complete and proper
hand washing should occur thereafter

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Hospital area restrictions
Symptomatic patients should be restricted to their room and not be allowed to common areas of
the hospital (e.g., lobby, gift shop, cafeteria, children’s hospital playrooms and school rooms,
etc.) Ambulation in the hallways is allowed when part of medical care routine. (UW Health Low
quality of evidence, strong recommendation)

During ambulation, must patient must wear clean clothing or a clean hospital gown, thoroughly
perform hand hygiene before leaving the room or wear gloves, and refrain from contact with
other patients. Staff accompanying the patient is expected to wear clean PPE. Any gloves
worn by staff and/or the patient should not be used to push elevator buttons or come into
contact with other common surfaces. These precautions are in accordance with UW Health
policy 4.1.8 Standard Precautions and Isolation and for more information, refer to UW Health
policy 4.1.8 Standard Precautions and Isolation plan.
Infection control in the ambulatory clinic
If a patient presents with diarrhea and there is concern for CDI in the ambulatory setting, all
clinicians and clinic staff should follow staff specific precautions as noted in Table 2, prior to
entering the patient’s room. (UW Health Low quality of evidence, strong recommendation) Example
scenarios where enhanced contact precautions should be followed in the ambulatory clinic
setting include:
• Patient with active CDI flag in medical record who presents to clinic with diarrhea
• Patient that presents to clinic with chief complaint of diarrhea and states having 5 bowel
movements per day when normally has only 2 bowel movements a day
• Patient who completed treatment for CDI infection and had resolution of symptoms but
presents to clinic with diarrhea and suspicion for CDI relapse

In addition, following the patient’s visit, cleaning should be done with sporicidal agent (e.g.,
bleach, oxycide) and not CaviWipes.
Infection control at home
It is strongly recommended that clinicians counsel patients and family members appropriately on
infection control precautions to conduct at home. (UW Health Low quality of evidence, strong
recommendation) Some key infection control precautions to emphasize include:
• Cleaning the home with bleach versus other household cleaners/detergents
• Washing hands with soap and water often, especially after going to the bathroom and
before handling food. Use cloth towels once only or use disposable towels.
• Consider using disposable gloves when changing diapers/disposable undergarments of
infected individual. Diapers should be disposed of properly and hands washed with soap
and water after disposing gloves.
• If possible, designate a bathroom for the affected household member/patient’s use only.
• Launder linens and clothing with bleach, wash with warm/hot water, and dry on non-low
heat setting. Clean and disinfect laundry “basket” with bleach between handling clean
and dirty laundry.

Additional infection precautions can be found in the Health Facts for You- What you Need to
know about Clostridium difficile Infection.
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Diagnosis
Clinical Characteristics and Risk Factors
Adult Patients:
Testing of adult patients without diarrhea or risk factors should be avoided.
21
(UW Health
Moderate quality of evidence, strong recommendation) In rare cases, patients may present with ileus
and/or colonic distention in the absence of diarrhea.
4


In addition to the following, risk of CDI is also known to be proportional to the total amount of
antibiotic exposure on a hospital unit.
20
Individual risk factors for first infection with Clostridium
difficile in adult patients with diarrhea are listed in Table 3.
2,4,5,27,28


Table 3. Risk factors for first infection with Clostridium difficile in adults with diarrhea
Risk factors for C. diff infection
• Exposure to antimicrobial agents and exposure to multiple antimicrobials especially:
o High-risk antibiotics (Table 1)
o Two or more antibiotics
• Increasing age (in particular > 64 years of age)
• Prior hospitalization for any reason within last 90 days
• Current hospitalization (LOS > 7 days)
• Immunosuppression (e.g. HIV, solid organ or hematopoietic stem cell transplant)
• Comorbidities (e.g., cystic fibrosis, inflammatory bowel disease, diabetes mellitus, chronic kidney
disease)
• Cancer chemotherapy
• Gastrointestinal surgery
• Manipulation of GI tract for any reason:
o Gastrostomy or jejunostomy tube feedings
o H
2
blockers
o Proton Pump Inhibitors
• Manipulation of GI tract for any reason (e.g., gastrostomy or jejunostomy tube feedings )



Pediatric Patients:
Although the epidemiology of Clostridium difficile infection in children has shown an increase in
incidence over the past decade, Clostridium difficile infection remains much less common and
when present, less severe in children than adults.

The studies on risk factors for CDI in children are limited; however, observational studies
suggest risks similar to adults (i.e., recent antibiotic exposure, immunosuppression including
receipt of immunosuppressive therapy, inflammatory bowel disease, renal insufficiency,
manipulation of the GI tract with gastrostomy and jejunostomy tubes or impairment of humoral
immunity.
14,25
Children with malignancy are at highest risk of CDI among hospitalized children.
29

Diagnostic Testing
Testing for Clostridium difficile or its toxins should be done only on diarrhea (unformed stool),
unless ileus due to Clostridium difficile is suspected.
4,27
(SHEA-IDSA Evidence Grade B, Category
II) Polymerase chain reaction (PCR) testing is sensitive and specific and is recommended for
standard diagnostic testing.
4
(UW Health Moderate quality of evidence, strong recommendation)

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Repeat testing for Clostridium difficile by PCR for diagnostic purposes is strongly discouraged
and testing for cure (i.e., at end of treatment) is not recommended.
4,14,25
(SHEA-IDSA Grade
B, Category III) It is estimated that 50-65% of patients remain PCR positive at 14 days following
initial diagnosis (i.e., after completing a course of treatment and without clinical signs and
symptoms of infection). These patients should not be retested without a change in clinical status
suggesting a CDI relapse.
30,31
Testing directly for cytotoxin by cell culture methodology can be
considered at the advice and consultation with Infectious Disease and Gastroenterology.

Direct visualization via colonoscopy or histologic findings of pseudomembranous colitis can also
infer Clostridium difficile infection.
4,14


Adult Patients:
Adult patients experiencing diarrhea (≥ 3 unformed stools in the previous 24 hours) with CDI risk
factors and no alternate etiology for diarrhea should be tested for Clostridium difficile toxin. (UW
Health Moderate quality of evidence, strong recommendation) Patients without diarrhea or risk factors
should not be tested. Adult patients with inflammatory bowel disease patients experiencing flare
symptoms should also be tested and isolated given the prevalence of Clostridium difficile
infection in patients with IBD (1.7% compared to 0.4% in general population).
2


Pediatric Patients:
In the pediatric population, asymptomatic carriage of Clostridium difficile can be as high as 70%
in infants in the first month of life, averaging 30-40% in the first two years of life and < 3% by
age 3.
14,32
Clinical illness in children less than 12 to 24 months is rare. Additionally, infants and
toddlers frequently have soft and loose stools, the cause of which can be multifactorial.
Therefore, laboratory testing for Clostridium difficile in infants < 1 year of age is discouraged
unless in the presence of Hirschsprung’s disease or other severe motility disorders, or in an
outbreak situation.
14
(UW Health High quality of evidence, weak/conditional recommendation)

Testing can be considered in children age 12 to 36 months with the appropriate clinical findings
(i.e., > 3 diarrheal stools in 24 hours and additional risk factors). However, alternative diagnoses
(i.e., antibiotic associated diarrhea, other microbial etiologies) should first be considered in this
age group as the false-positive rate for Clostridium difficile as a causative agent of disease is
high in the younger population.
14,25,33
(UW Health Class Low quality of evidence, weak/conditional
recommendation) It is reasonable to test pediatric patients age 3-17 years with the appropriate
clinical findings (i.e., > 3 unformed stools in the previous 24 hours) and associated risk factors
for Clostridium difficile toxin.
14
(UW Health Moderate quality of evidence, weak/conditional
recommendation)

Table 4 summarizes who to test and when to not test. For specific testing guidance in the
inpatient setting, refer to the Adult Inpatient Clostridium difficule Infection Testing algorithm and
Pediatric Inpatient Clostridium difficule Infection Testing algorithm.


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Table 4. When to test for C Diff Infection
Population
When to test… DO NOT test…
Adults
• Patient with diarrhea (≥ 3 unformed
stools* in the previous 24 hours),
particularly those with risk factors, and no
alternative etiology for diarrhea
• Patients with IBD with flare symptoms
• Hospital admitted patients within first 48
hours of admission with complaints of or
any unexplained loose stools prior to
admission (see testing algorithm)
• Patient treated for CDI with prior
resolution of symptoms who may have
new infection (i.e., symptomatic,
diarrhea)
• Patients < 12 months without
appropriate clinical findings

• Patients on laxatives

• Any admitted patient age ≥ 3 years
with < 3 unexpected liquid/loose
stools after 48 hours of admission

• A patient still taking oral
vancomycin for CDI

• Patients treated for CDI without
complete resolution of symptoms
with possible relapse

• If pt had a C diff test result within
last 7 days

• Asymptomatic patients for nursing
home placement

• Patient near end of CDI
treatment (i.e., testing for cure)

Pediatric
• Patients ≥ 12 months with appropriate
clinical findings (≥ 3 unformed stools* in
the previous 24 hours), particularly those
with risk factors and no alternative
etiology for diarrhea
• Hospital admitted patients > 3 years
within first 48 hours of admission with
complaints of or any unexplained loose
stools prior to admission (see testing
algorithm)
• Patient treated for CDI infection with
resolution of symptoms who may have
new infection

*Stool episodes should be measured as ≥ 3 unformed stools from patient’s baseline bowel
movements per day

Antimicrobial Treatment of Initial Infection

Daily assessment for signs and symptoms is necessary to assess efficacy of all treatments.
When feasible, discontinuation of therapy with inciting antimicrobial agent(s) as soon as
possible is recommended as the first step in treatment.
7,14,25
(UW Health High quality of evidence,
strong recommendation)

In general, antiperistaltic agents should be avoided in patients with suspected or confirmed CDI
since they may obscure symptoms and precipitate toxic megacolon.
4,14
(SHEA-IDSA Evidence
Grade C, Category III)

Multiple oral agents provide redundant coverage and should not be given simultaneously.
Examples include oral vancomycin and oral metronidazole OR oral vancomycin and oral
fidaxomicin. (UW Health Low quality of evidence, weak/conditional recommendation) Oral
metronidazole is 90% absorbed and it is not recommended to give concomitantly with full-dose
intravenous metronidazole. (UW Health Moderate quality of evidence, weak/conditional
recommendation) Oral vancomycin and fidaxomicin are NOT absorbed from the GI tract. If
treatment of non-CDIs outside of the GI tract requires vancomycin, the intravenous form can be
given simultaneously with the oral form without risk of toxicity. Conversely, patients being
treated with intravenous vancomycin will NOT achieve adequate levels in the GI tract and are
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NOT being effectively treated for CDI. (UW Health Very low quality of evidence, weak/conditional
recommendation)

The duration of therapy generally should not exceed 14 days for most patients. Exceptions may
include treatment of severe Clostridium difficile infection or treatment of a relapse of disease
AND extended therapy while on broad-spectrum or other antibiotics with the potential to
increase rates of Clostridium difficile relapse.
7
(UW Health Class Low quality of evidence,
weak/conditional recommendation)

Adult Patients:
Therapy without diagnostic suspicion is not appropriate.
4
(UW Health Low quality of evidence,
weak/conditional) The decision to treat CDI (Table 6) should be based upon the severity of
infection as determined by thoughtful clinical decision making.
3


Adults with mild disease typically present with diarrhea with minimal additional findings. For
treatment of mild disease, begin metronidazole 500 mg PO three times daily for 10 to 14 days.
4

(UW Health Class High quality of evidence, strong recommendation) Patients with mild CDI who are
intolerant/allergic to metronidazole, or in women who are pregnant/breastfeeding, should begin
vancomycin at standard dosing, 125 mg PO four times daily for 10-14 days.
3
(UW Health High
quality evidence, strong recommendation) Patients with a history of neuropathy or current alcohol
use which cannot be stopped during therapy should receive vancomycin over metronidazole.

Table 5 outlines criteria typically associated with adult patients who have moderate to severe or
severe CDI.

Table 5. Criteria to consider for Moderate to Severe CDI in Adults
Moderate to severe CDI in adults if: Severe, complicated CDI in adults if:
• immunocompromised (e.g., HIV, chronic
steroid use, chemotherapy)
• on hemodialysis
• or meet some of the following criteria:
o age > 60 years
o albumin < 2.5 mg/dL
o WBC > 15, 000 cells/mm
3

o abdominal tenderness, or
o elevated serum creatinine > 1.5x
the premorbid level.

• ICU/IMC admission
• Ileus
• Toxic megacolon
• Diverting ileostomy, or
• Significant abdominal distension
• SIRS
• Hypotension with or without required use of
vasopressors felt to be related to CDI
• WBC > 30,000 cells/mm
3
or < 1,000
cells/mm
3

• Serum lactate > 2.2. mmol/L, or
• End organ failure felt to be related to CDI.


Ultimately, the distinction between mild and moderate to severe disease is a clinical decision
based on age, comorbidities, and the constellation of other findings. For treatment of moderate
to severe disease in adults, begin vancomycin 125 mg PO four times daily for 10 to 14 days.
(UW Health High quality of evidence, strong recommendation) Dose escalation of vancomycin is
rarely necessary as intraluminal concentrations of vancomycin far exceed the concentrations of
Clostridium difficile.
34


As above, the ultimate decision regarding severity should be made considering the entirety of
the individual case. For treatment of severe disease with additional complications (such as toxic
megacolon, systemic inflammatory response syndrome, etc.), in addition to surgical
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consultation, begin vancomycin 500 mg PO/NG four times daily PLUS metronidazole 500 mg IV
three times daily.
3,4
Tigecycline 100 mg IV once then 50mg IV every 12 hours may be
considered as an alternative for metronidazole IV in patients with severe refractory CDI when
there is a need for continuation of concomitant anti-infectives which may worsen the
condition.
35,36
(UW Health Low quality of evidence, weak/conditional recommendation)

For treatment of severe CDI in adult patients with ileus or patients with diverting ileostomy
consider adding vancomycin rectal instillation.
4,35
(UW Health Low quality of evidence,
weak/conditional recommendation) The recommended dose is 500 mg in approximately 100 mL
normal saline per rectum four times daily.
4
Vancomycin rectal administration is NOT routinely
recommended in neutropenic patients due to the risk of infection with manipulation of the
rectum. (UW Health Very low quality of evidence, weak/conditional recommendation)

Table 6. Adult Treatment Recommendations for First Clostridium difficile Infection
Infection Severity Adult Treatment Recommendations for First Infection
Mild
Metronidazole 500 mg PO three times daily for 10-14 days.*

*Exceptions: Patients with an intolerance/allergy, who are pregnant, have a
history or neuropathy, or cannot stop alcohol use during therapy should
receive vancomycin.
Moderate to Severe Vancomycin 125 mg PO four times daily for 10-14 days
Severe, complicated
Vancomycin 500 mg PO/NG four times daily
PLUS
Metronidazole 500 mg IV three times daily**

**Exceptions: Patients with severe refractory CDI and need to continue
concomitant anti-infectives may be considered for Tigecycline 100 mg IV once
then 50 mg IV every 12 hours as alternative.
Severe, ileus or
diverting ileostomy
Consider adding vancomycin 500 mg rectally in approximately 100 mL normal
saline four times daily

Pediatric Patients:
When possible, the first step in therapy is discontinuation of inciting antimicrobial agent(s) and
may suffice in many instances.
14,37
Therapy without diagnostic suspicion is usually not
appropriate.
4
(UW Health Low quality of evidence, weak/conditional recommendation) Treatment
decisions should be based upon the severity of Clostridium difficile symptoms (Table 7).
14,25


Metronidazole is recommended as first line therapy for initial infection in pediatric patients with
mild to moderate disease (i.e., diarrhea, low grade fever, mild abdominal pain). The suggested
dose for metronidazole is 30 mg/kg/day enterally in 4 divided doses, with a maximum daily dose
of 2,000 mg/day.
14,25
(UW Health High quality of evidence, weak/conditional recommendation)

Severe disease should be treated with enteral vancomycin or vancomycin by enema with
suggested dosing of 40 mg/kg/day in 4 divided doses (max 2,000 mg/day). Vancomycin may
also be given with or without intravenous metronidazole 30-40 mg/kg/day in 3 divided doses
(max 1500 mg/day).
14,25
(UW Health High quality of evidence, weak/conditional recommendation)


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Table 7. Pediatric Treatment Recommendations for First Clostridium difficile Infection
37

Infection
Severity
Pediatric Symptoms and Criteria
Pediatric Treatment Recommendations for 1st
Infection
Mild to
Moderate
Any of the following:
• Watery diarrhea
• Low grade fever
• Mild abdominal pain
Metronidazole 30 mg/kg/day enteral in 4 divided doses
(max 2,000 mg/day)
Severe*
Any of the following:
• Systemic toxicity
(e.g., high-grade fever,
rigors)
• Hospitalization in the PICU
• Pseudomembranous
colitis
• Toxic megacolon
Severe disease:
Vancomycin 40 mg/kg/day enteral or rectal enema in 4
divided doses (max 2,000 mg/day)

OR
Severe, complicated disease:
Vancomycin 40 mg/kg/day enteral or rectal enema in 4
divided doses (max 2,000 mg/day) PLUS
Metronidazole 30-40 mg/kg/day in 3 divided doses
(max 2,000 mg/day)
*Note: Neutropenic patients, or those having underlying gastrointestinal disease such as inflammatory bowel
disease or Hirschsprung’s disease, are more likely to have severe disease.
Relapse Prevention in Adult Patients
Recurrence of CDI is highest in the 7-14 days after completion of initial therapy. The risk of
recurrence also increases as the number of recurrences increase.
4,7
Risk factors for recurrent
CDI include:
8,38

• All of the factors as outlined for initial infection (see above)
• Continued exposure to organisms (i.e., using a contaminated toothbrush, incorrectly
cleaning home environment or clothing, failing to perform appropriate hand hygiene)
• Relapsing CDI from endogenous source (i.e. spores in GI tract)
• Poor host IgG antibody response to toxin A

Probiotics have not been shown to be effective as adjunctive therapy for treatment or in the
prevention of relapse or recurrent CDI. In addition, there is a risk of developing a bloodstream
infection in patients who are heavily immunosuppressed.
17,39,40
(UW Health Class Very low quality
of evidence, weak/conditional recommendation) For adult patients who are not
immunocompromised, it is reasonable to consider probiotics for the prevention of the index of
primary infection given the use of probiotics in these patients is relatively harmless. Use of
probiotics in secondary and subsequent relapses is not recommended at this time.

For adult patients with a history of CDI in the last 90 days and who are receiving antibiotics for a
non-C. Difficile infection, prophylactic low dose vancomycin (vancomycin 125 mg orally twice
daily) or low dose metronidazole (500 mg orally once or twice daily) may be reasonable for CDI
relapse prevention. Continuation of low dose vancomycin or low dose metronidazole may also
be considered in a patient who has a history of CDI, is being treated for a non-C. Diff infection
and who subsequently develops a new CDI while receiving the inciting antibiotic.

The following case examples depict scenarios in which low dose prophylaxis vancomycin may
be considered.

Case Example #1: A 65 year old male who is undergoing chemotherapy for colon cancer was
treated for C. Diff infection in January 2016. Patient is admitted to hospital in February 2017 for
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pneumonia. Patient receives antibiotics for pneumonia and is also given prophylactic low-dose
vancomycin. Patient is instructed to take low-dose vancomycin for duration of pneumonia
antibiotic course and to continue 5 days thereafter.

Case Example #2: A 60 year old female with diabetes is being treated for endocarditis. While
on antibiotic therapy for endocarditis infection, patient gets a CDI. Patient then continues her
antibiotics for endocarditis, receives therapeutic dosing for vancomycin to treat CDI for 14 days
and then is instructed to take low-dose vancomycin to prevent CDI relapse for the duration of
endocarditis antibiotic regimen and continue the low-dose vancomycin for 5 days thereafter.

Case Example #3: A 40 year old male patient is receiving antibiotics for a complicated intra-
abdominal infection (cIAI). Antibiotics are planned for 14 days duration. On day 3 of therapy,
patient develops a Clostridium difficile infection. The patient receives 11 days of concomitant
cIAI and C diff therapy. Patient should receive treatment dosing (vancomycin orally 4 times a
day) for 7 days following completion of cIAI antibiotic therapy.

It is recommended that for patients who develop a CDI while on a concomitant broad-spectrum
antibiotic, the patient should complete at least 10-14 days of Clostridium difficile treatment and
receive at least 7 days of CDI treatment therapy without concomitant broad-spectrum antibiotic
therapy. (UW Health Class Low quality of evidence, weak/conditional recommendation)

For patients who are treated with low-dose vancomycin prophylaxis, it is recommended that the
patient continue low-dose CDI prophylaxis for 5-7 days following discontinuation of primary
antibiotic (as described in case example #1.)

In stable adult patients receiving vancomycin, conversion to metronidazole may be considered
to reduce the risk of emergence of vancomycin-resistant enterococci and prevent development
of metronidazole-associated neuropathy.
41,42
(UW Health Moderate quality of evidence,
weak/conditional recommendation) Due to consideration for medication cost, metronidazole may be
considered when the discussion of neuropathy risk is completed.

If long-term therapy (usually greater than 14 days) low-dose therapy is being considered in
adults, the preferred agent is oral vancomycin, in light of the risk of neurotoxicity. This is
because the use of metronidazole and that fidaxomicin has no data to support prophylactic use.
(UW Health Very low quality of evidence, weak/conditional recommendation)
Antimicrobial Treatment of Relapse/Recurrent Infection
Adult Patients:
Adult patients relapsing after primary treatment with metronidazole should be given a trial of
vancomycin before considering fidaxomicin. (UW Health Moderate quality of evidence,
weak/conditional recommendation)

Sequential therapy with vancomycin followed by rifaximin may be effective for the treatment of
recurrent CDI in adults.
43
Vancomycin taper as described in Table 3 below should be attempted
first. Vancomycin pulse after taper is: vancomycin 125 to 500 mg PO every 3 days for up to 3
weeks.
44
(UW Health Low quality of evidence, weak/conditional recommendation) If vancomycin is to
be used for subsequent recurrences, consider use of vancomycin followed by rifaximin 200
mg/day PO 2 times daily for 14 days. (UW Health Low quality of evidence, weak/conditional
recommendation)

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There is limited evidence to support use of G.I. lavage (e.g., GOLYTELY solution) as an adjunct
to agents routinely used to treat chronic, relapsing Clostridium difficile infection. However, G.I.
lavage may be useful for clearing Clostridium difficile organisms, spores, and associated toxins
from the intestine of patients with relapsing infections.
45
(UW Health Low quality of evidence,
weak/conditional recommendation) Use of this product associated with surgical temporizing
ileostomy may be considered.

For adult patients with BI/NAP1/027, there was no clinical difference in benefit between
vancomycin and fidaxomicin.
46
Therefore, vancomycin is the preferred agent and fidaxomicin
should be used for non-NAP1 strains only. (UW Health Moderate quality of evidence, strong
recommendation).

Table 8. Adult Treatment Recommendations for Relapse Clostridium difficile Infection
Relapse Adult Treatment Recommendations for Relapse
First Recurrence
Vancomycin 125 mg PO four times daily for 10-14 days*

*Exception: For adult patients with BI/NAP1/027, there was no clinical
difference in benefit between vancomycin and fidaxomicin. Therefore,
vancomycin is the preferred agent and fidaxomicin should be used for non-
NAP1 strains only.
Second Recurrence or
Further Recurrence
Vancomycin Taper: Vancomycin 125 mg PO twice daily for 7 days, then 125
mg PO daily for 7 days, then 125 mg PO every 2 days for 7 days, then 125 mg
PO every 3 days for 7 days then cease treatment
4,44
(UW Health Class IIb,
Level of Evidence C)

Vancomycin pulse after taper: Vancomycin 125-500 mg PO every 3 days for
up to 3 weeks
Consider consultation by Gastroenterology or Infectious Disease and
Fidaxomicin 200 mg PO twice daily for a maximum of 10 days
Consider Vancomycin 125 mg PO four times daily for 10-15 days followed by
Rifaximin 200 mg/day PO twice daily for 14 days

Fidaxomicin
46
Adult patients with relapse or recurrence may be considered candidates for fidaxomicin under
the guidance of Gastroenterology or Infectious Disease. The ability for a patient to pay for
fidaxomicin as an outpatient should be assessed prior to initiating inpatient fidaxomicin
treatment due to cost. The recommended dose of fidaxomicin is:
• Fidaxomicin 200 mg orally twice daily for a maximum of 10 days. (UW Health High quality
of evidence, strong recommendation)
• Treatment should NOT be extended beyond 10 days.

Fidaxomicin is not FDA-approved in children, and is typically reserved for adult patients with the
following conditions:
• Documented (PCR positive or colonoscopy proven) recurrent CDI requiring
hospitalization. (UW Health Moderate quality of evidence, weak/conditional recommendation)
• Relapse during current hospitalization. (UW Health Moderate quality of evidence,
weak/conditional recommendation)
• Outpatient with relapse(s) of disease not requiring hospitalization (UW Health Class Low
quality of evidence, weak/conditional recommendation)
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• Patients with documented low levels of neutralizing antibodies to Clostridium difficile
(since this test is not available with rapid turnaround time, use under this indication
would likely take 10-14 days). The role of both IVIG infusion and fidaxomicin is uncertain
at this time. (Low quality of evidence, weak/conditional recommendation)
• Patients who have relapsed within 4 weeks of treatment of fidaxomicin are not
candidates for repeated courses. (UW Health Low quality of evidence, weak/conditional
recommendation)
• Patients who have relapsed within more than 4 weeks of treatment of fidaxomicin,
received antibiotics with these 4 weeks, and have recurrent CDI may be considered for
repeated courses of fidaxomicin. (UW Health Low quality of evidence, weak/conditional
recommendation)
• Fidaxomicin has been shown to be equally efficacious as vancomycin for primary
treatment, and may result in less frequent relapse. However, since patients were only
followed for 30 days, the prevention was not fully determined. Fidaxomicin may be
prescribed for first episode CDI under unusual circumstances with the approval of
Infectious Disease or Gastroenterology.

Appendix D outlines the treatment pathway for adult patients with CDI.

Pediatric Patients:
• In pediatric patients with first recurrence, metronidazole is recommended. (UW Health
High quality of evidence, weak/conditional recommendation) Metronidazole should be
administered 30 mg/kg/day enterally in 4 divided doses with a maximum dose of 2,000
mg/day.
14


• For subsequent recurrences of CDI in pediatric patients a vancomycin taper may be
considered, especially under consultation by Pediatric Infectious Disease or Pediatric
Gastroenterology. The pediatric vancomycin taper can be: vancomycin 10 mg/kg 4 times
daily for 10-14 days, then vancomycin 10 mg/kg 2 times daily for 7 days, then 10 mg/kg
once daily for 7 days, then 10 mg/kg every 2-3 days for 2-8 weeks
(max = 125 mg/dose).
47
(UW Low quality of evidence, weak/conditional recommendation)

• Studies are limited in children for the use of rifaximin after a vancomycin taper for
subsequent recurrences and is not recommended.
14


Appendix E outlines the treatment pathway for pediatric patients with CDI.
Non-Antimicrobial Interventions for Recurrent Infection
Intravenous Immune Globulin (IVIG)
Randomized control trials have demonstrated conflicting results and conflicting evidence of
benefit for the use of intravenous immune globulin (IVIG) treatment for CDI. IVIG failed to
decrease the risk of colectomy or mortality in a study of pair matched adults with severe CDI,
however no testing of IgG levels was performed.
48
Clinical studies did NOT measure Clostridium
difficile neutralizing antibody titers in the IVIG preparations. Therefore, not all patients with low
titers may benefit from IVIG.

Use of this therapy should be indicated by Infectious Disease and Gastroenterology, Pediatric
Infectious Disease and Pediatric Gastroenterology attending physicians, as outlined within the
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UW Health Intravenous Immune Globulin (IVIG) – Pediatric/Adult – Inpatient/Ambulatory Clinical
Practice Guideline.
Bezlotoxumab
Bezlotoxumab is a monoclonal antibody that binds and neutralizes C diff toxins A and B
respectively.
33
In clinical studies, bezlotoxumab has demonstrated efficacy in adults receiving
antibiotic therapy and bezlotoxumab for CDI versus antibiotic therapy alone for the prevention of
CDI recurrence. Thus, bezlotoxumab is not indicated for treatment of CDI and only for
prevention of CDI recurrence.

It is recommended to adhere to the following when utilizing bezlotoxumab in patients at UW
Health for CDI recurrence prevention: (UW Health Low quality of evidence, weak/conditional
recommendation)
• Bezlotoxumab should be used in conjunction with a C. difficile treatment (i.e.,
vancomycin or metronidazole).
• Bezlotoxumab should be used with Infectious Diseases approval (through ID consult).
• It is reserved for patients with a new C. difficile PCR-confirmed diagnosis AND failure of
fecal microbiota transplant (FMT) on two occurrences with confirmation that fecal
microbiota therapy (FMT) was performed according to administration protocol and not by
colonoscopy, or
• FMT failure by colonoscopy on one occurrence, or
• The patient has one of the following contraindications to receiving FMT:
o is profoundly immunosuppressed
o is CMV-negative transplant patient
o is admitted to ICU level of care with C. difficile-related sepsis.

Additionally, it is recommended that bezlotoxumab administration occur no sooner than 72
hours after initiation of C. difficile treatment regimen (i.e., vancomycin or metronidazole) to
maximize effect of bezlotoxumab in preventing recurrence. For additional information on
bezlotoxumab use at UW Health, refer to Lexicomp internally.
Fecal microbiota therapy (FMT)
Due to the growing epidemic of CDI, alternative therapies for recurrent CDI are emerging
including fecal microbiota therapy. FMT is the delivery of stool from a healthy donor into the
colon of a patient with recurrent CDI, via the upper gastrointestinal route (nasoduodenal
infusion), via the colon by enema, or oral administration with frozen fecal microbiota capsule.
Fecal bacteriotherapy has emerged as an effective and safe option for patients with relapsing
CDI, refractory to other therapies.
49


Fecal microbiota therapy may be considered in pediatric (UW Health Class Moderate quality of
evidence, weak/conditional recommendation) or adult patients (UW Health Low quality of evidence,
weak/conditional recommendation) who meet the following eligibility criteria.
50-54
All FMT
candidates should be assessed by an Infectious Disease or Pediatric Infectious Disease
provider. All cases should also be coordinated and managed by a specialist (i.e., Infectious
Disease and Gastroenterology, Pediatric Infectious Disease or Pediatric Gastroenterology
attending physicians).


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Eligibility Criteria for FMT:
• Patients must have documented Clostridium difficile infection with stool testing for
Clostridium difficile and documented relapse of this infection despite appropriate
treatment (i.e. 3
rd
episode of CDI). Relapsing CDI is defined by patients who have
received an initial 10-14 day course of oral metronidazole or oral vancomycin (first
episode); followed by one recurrence unresponsive to an extended tapering regimen
(usually 4 to 8 weeks) of vancomycin and/or 10-day course of fidaxomicin.
• Patients should not be considered eligible for FMT if currently completing a course of
anti-infectives (other than targeted CDI therapy with oral vancomycin or oral
metronidazole or oral fidaxomicin) for other infectious conditions.
• Patients should generally be clinically stable in the outpatient setting to qualify for the
procedure.

UW Health Implementation
Potential Benefits:
• Appropriate diagnosis, treatment and prevention of CDI in pediatric and adult patients
• Decrease in overall hospital acquired infections rate

Potential Harms:
• Side effects and adverse events associated with use of medical and pharmacotherapy
treatments

Pertinent UW Health Policies & Procedures
1. UWHC Policy 11.14- Collection of Stool Specimens for Laboratory Examination
2. UWHC Policy 13.07- Standard Precautions and Transmission-based Precautions (Isolation)
for Inpatient Settings
3. UWHC Policy 13.08- Hand Hygiene
4. UWHC Policy 13.28- Precautions & Transmission Based Precautions
5. UWHC Policy 13.29- Isolation Practice for Multi-Drug Resistant Organisms
6. UWHC Policy 6.1.9- Restricted Primarily Ambulatory Administered Medications in
Hospitalized Patients
7. UWHC Policy 6.1.5- Formulary Restricted Clinic Administered Medication
Pharmacy Department Review and Use of Non-UW Health Supplied Medications
Administered in Clinics
8. Patient Header Infectious Flags- Inpatient and Ambulatory Settings within CSC
9. Infection Prevention and Control Program
10. Cleaning and Disinfection Instructions

Patient Resources
1. HFFY #7219- What You Need to Know About Clostridium difficile Infection
2. HFFY #7575- Fecal Bacteriotherapy
3. HFFY #7585- Getting Ready for a Fecal Bacteriotherapy Procedure
4. HFFY #7602- What You Need To Know as a Stool Provider
5. Healthwise: C Dif Colitis
6. Healthwise: C dif colitis: Pediatric
7. Health Information- Clostridium difficile Colitis
8. Kids Health- Stool Test: C. Difficile Toxin

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Guideline Metrics
1. UW Hospital Clinical definition- Hospital Acquired Clostridium difficile Infection
(Measured per rate of hospital onset Clostridium difficile infection rate per 10,000 patient
days.)
2. National Health Safety Network (NHSN)- LabID definition (Measured per amount of
observed to expected ratio of infections, and reported as Standardized Infection Ratio
(SIR).)

Implementation Plan/Clinical Tools
1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the
guideline recommendations (such as the following) will be reviewed for consistency and
modified as appropriate.

Companion Documents
1. UW Health Intravenous Immunoglobulin (IVIG) - Pediatric/Adult - Inpatient/Ambulatory
Clinical Practice Guideline
2. Infection Control and Testing Recommendations for C diff Infection

Best Practice Alerts (BPA)
C Diff Positive Result- Last 48 Hours Not On Tx [3000900]

Delegation Protocols
Clostridium difficile – Adult – Inpatient [96]
Clostridium difficile Testing – Adult – Infectious Disease Clinic [107]

Order Sets & Smart Sets
IP – Clostridium difficile Treatment – Adult – Supplemental [5316]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and
treatment of patients. This guideline outlines the preferred approach for most patients. It is not
intended to replace a clinician’s judgment or to establish a protocol for all patients. It is
understood that some patients will not fit the clinical condition contemplated by a guideline and
that a guideline will rarely establish the only appropriate approach to a problem.

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Appendix A. Evidence Grading Scheme(s)

Figure 1. GRADE Methodology adapted by UW Health


GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate
We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong
The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.






Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
08/2017CCKM@uwhealth.org

Does the patient have LESS than 3 unexpected liquid/loose stools beyond
their known or established baseline within the past 24 hours?
1, 2, 4
Do NOT Test
Can the diarrhea be the result of the patient currently or recently (past 48
hours) being introduced to a new medication or therapy associated with
diarrhea such as any of the following:
stool softeners, laxatives, enemas, bowel preps, lactulose, tube feeds, or
oral contrast?
5
Do NOT Test
Consider altering therapy. Re-evaluate 24-48
hours after suspending affecting agent. If agent
cannot be suspended, exercise clinical
judgment and if appropriate proceed to the
next (“No”) step below.
Yes
No
Is the patient low-risk (i.e. afebrile, no elevated WBC, no abdominal pain,
no recent antibiotic use, not an IBD patient nor any recent/frequent
healthcare encounters)?
3
Yes
Do NOT Test
Pre-test probability is low. Consider
alternative causes of diarrhea.
No
ORDER the Test
Continue enhanced contact
isolation.
Do not test for cure.
In the FIRST 48 hours of admission
Does the patient complain of or have any unexplained loose
stools prior to admission?
Do NOT Test
No
AFTER 48 hours following admission
Yes
No
DISCLAIMER: Laboratory limit: 1 Test every 7 days.
Complex patients, including obstruction cases, may
not readily conform to this algorithm. As always,
sound clinical judgement should be applied in
conjunction with the information provided here. In
some instances, expert opinion should be solicited.
Adult Inpatient Testing Algorithm for Clostridium difficile Infection (CDI)
ORDER the Test
Place on enhanced contact isolation.
Yes
Place patient on enhanced contact isolation. Maintain isolation until
diarrhea resolves or an alternative, non-infectious cause of diarrhea has
been determined.
Last reviewed/revised: 07/2017
Contact CCKM for revisions.
Clostridium difficile – Pediatric/Adult – Inpatient/Ambulatory Guideline
References:
1.Surawicz CM, et al. Am J Gastroenterol. 2013 Apr;108(4):478-98.
2. Peterson, LR, Robicsek A. Ann Intern Med 2009; 151:176-179.
3. http://www.wakehealth.edu/uploadedFiles/User_Content/SchoolOfMedicine/Departments/CAUSE/
PPT_and_PDF_files/CDI%20Decision%20Support%20Tree%20Algorithm%20-%2006%2026%2014.pdf
4. Cohen S. et al Infect Control Hosp Epidemiol. 2010 May;31(5):431-55.
5. Brazier JS. J Antimicrob Chemother1998; 41
6. http://www.uptodate.com/contents/clostridium-difficile-in-adults-treatment
7. Bagdasarian N, Rao K, Malani PN. JAMA. 2015;313(4):398-408.
NOTE: It is important to consider whether the diarrhea could be a result of recent or overuse of
medications or therapies associated with diarrhea including: stool softeners, laxatives, enemas,
bowel preps, etc. Further, more than 55% of positive CDI tests are in clinic or on admission to
UW Health suggesting CDI is more common in the community than traditionally believed. Do
not test asymptomatic patients but thoroughly evaluate GI symptoms on admission and
consider CDI early on as a potential causative pathogen in symptomatic patients
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
08/2017CCKM@uwhealth.org

Does the patient have LESS than 3 unexpected liquid/loose stools beyond
their known or established baseline within the past 24 hours?
1, 2, 4
Do NOT Test
Can the diarrhea be the result of the patient currently or recently (past 48
hours) being introduced to a new medication or therapy associated with
diarrhea such as any of the following: stool softeners, laxatives, enemas,
bowel preps, lactulose, tube feeds, narcotic withdrawal or oral contrast?
5
Do NOT Test
Consider altering therapy. Re-evaluate 24+
hours after suspending affecting agent-
especially purgatives. If agent cannot be
suspended, exercise clinical judgment and if
appropriate proceed to the next (“No”) step
below.
Yes
No
Did the diarrhea resolve/improve on its own prior to testing? Has the
order been placed and the specimen unable to be collected/obtained for
more than 8 hours?
Yes
Do NOT Test. If the order is placed and > 8
hours elapsed without bowel movement,
discuss with ordering provider. Remove
patient from isolation if infectious diarrhea is
no longer suspected.
No
ORDER the Test
Continue enhanced contact isolation.
Do not test for cure.
In the FIRST 48 hours of admission (patient age > 3 years)*
Does the patient complain of or have any unexplained loose stools
prior to admission? This includes pediatric patients with known
inflammatory bowel disease experiencing diarrhea.
Do NOT Test
No
AFTER 48 hours following admission (patient age > 3 years )*
Yes
No
DISCLAIMER:
Laboratory limit: 1 Test every 7 days.
Complex patients, including obstruction cases and
patients with inflammatory bowel disease may not
readily conform to this algorithm. As always, sound
clinical judgement should be applied in conjunction with
the information provided here. In some instances,
expert opinion should be solicited.
Pediatric Inpatient PCR Testing Algorithm for Clostridium difficile infection (CDI)
Place on enhanced contact isolation.
Strongly consider testing.
Yes
Place patient on enhanced contact isolation. Maintain isolation until
diarrhea resolves or an alternative, non-infectious cause of diarrhea has
been determined.
Last Reviewed: 08/2017
Clostridium difficile – Pediatric/Adult – Inpatient/Ambulatory Guideline
References. (7-11 peds specific)
1.Surawicz CM, et al. Am J Gastroenterol. 2013 Apr;108(4):478-98.
2. Peterson, LR, Robicsek A. Ann Intern Med 2009; 151:176-179.
3. http://www.wakehealth.edu/uploadedFiles/User_Content/SchoolOfMedicine/Departments/CAUSE/
PPT_and_PDF_files/CDI%20Decision%20Support%20Tree%20Algorithm%20-%2006%2026%2014.pdf
4. Cohen S. et al Infect Control Hosp Epidemiol. 2010 May;31(5):431-55.
5. Brazier JS. J Antimicrob Chemother1998; 41
6. Bagdasarian N, Rao K, Malani PN. JAMA. 2015;313(4):398-408.
7. http://archpedi.jamanetwork.com/article.aspx?doi=10.1001/jamapediatrics.2013.441
8. http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16941358
9. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/
landingpage.htm?issn=0891-3668&volume=30&issue=7&spage=610
10. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/
landingpage.htm?issn=0891-3668&volume=30&issue=7&spage=580
11. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/
landingpage.htm?issn=0891-3668&volume=34&issue=9&spage=919
NOTE: During 18 recent months at UW 79% of the 47 pediatric patients with CDI
were identified in clinic, the emergency department or within the first 48 hours of
admission. In a recent study, 23% of community onset pediatric cases had no risk
factors for CDI (5). Do not test asymptomatic patients but thoroughly evaluate GI
symptoms on admission and consider CDI early on as a potential causative
pathogen in symptomatic patients.
* Because of the high prevalence of asymptomatic carriage
of toxigenic CDI in infants and young children up to 3 years
of age, routine testing for CDI is not recommended. If
completed it should be conducted with testing for
alternative causes of diarrhea, such as norovirus and
rotavirus. CDI should not be assumed to be causative of
diarrhea unless there is no other plausible explanation.
Testing should NOT be completed in patients younger than 3 years of age.*
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
08/2017CCKM@uwhealth.org

C. Diff Infection
≥ 3 loose/liquid stools in previous 24 hours from
baseline bowel movement/day with risk factors
First
occurrence?
First
recurrence?
NO
Does pt have
severe disease?
YES
Intolerant/allergy
metronidazole or
needs alternative?
Refer to treatment for
second or further
recurrence
Consider
Infectious Disease or
Gastroenterology
consult if 3
rd
of more
episode CDI
NO
Is patient
candidate for
fidaxomicin?
Treat with
fidaxomcin 200mg PO twice
daily for 10 days
YES
Severe,
complicated pt or has
ileus/diverting
ileostomy?
Consider ID consult
For severe,complicated CDI:
Vancomycin 500mg PO/NG
4 times daily +
metronidazole 500 mg IV
3 times daily
For severe,ileus or diverting
ileostomy CDI:
Consider add
vancomycin 500 mg rectal
in approx. 100 mL NS
4 times daily
For moderate to severe CDI:
vancomycin 125 mg PO 4 times daily 10-14 days
NO
Moderate to Severe CDI if patient:
Immunocompromised (e.g., HIV, chronic steroid use,
chemotherapy), on hemodialysis, or meet some of following
criteria:
Age > 60 years
Albumin < 2.5mg/dL
WBC ≥ 15000 cells/mm3
Abdominal tenderness
Elevated serum creatinine 1.5x premorbid level
Second or Further Recurrence CDI Treatment
Vancomycin Taper: Vancomycin 125 mg PO twice daily
for 7 days, then 125 mg PO daily for 7 days, then 125
mg PO every 2 days for 7 days, then 125 mg PO
every 3 days for 7 days
Vancomycin pulse after taper: Vancomycin 125-500 mg
PO every 3 days for up to 3 weeks
Consider consultation by Gastroenterology or Infectious
Disease and Fidaxomicin 200 mg PO twice daily for a
maximum of 10 days
Consider Vancomycin 125 mg PO four times daily for
10-15 days followed by Rifaximin 200 mg/day PO twice
daily for 14 days
Consider alternative to metronidazole if :
Intolerant/allergy to metronidazole
Pregnant/breastfeeding
History of neuropathy
Current alcohol use that can’t be stopped for
therapy
Infection Control at Home counseling points:
Clean home with bleach
Wash hands with soap and water often
Designate bathroom for infected household
member
Launder linens/clothes with bleach in
warm/hot water
YES
҉ Remember! Enhanced contact precautions if patient is symptomatic and there’s CDI flag in chart! or high suspicion of relapse within 90 days of last positive test
YES
Relapse prevention/Management of Recurrence
Low dose metronidazole or low dose vancomycin may
be considered in patients who:
have a history of CDI and develop a new CDI while
taking an antibiotic for a non-CDI infection.
are being treated with antibiotic for a non-CDI
infection within 90 days of a CDI
Suggested dosing: metronidazole 500 mg PO once or
twice daily OR vancomycin 125 mg BID. Recommended
Low dose therapy for duration of non-CDI antibiotic
therapy and for 5-7 days thereafter
TEST THESE PATIENTS FOR CDI
 Patient with diarrhea (≥ 3 unformed
stools from baseline bm/day in the
previous 24 hours), particularly
those with risk factors, and no
alternative etiology for diarrhea
 Patients with IBD with flare
symptoms
 Patient treated for CDI with prior
resolution of symptoms who may
have new infection (i.e.,
symptomatic, diarrhea)
DO NO TEST if….
 Patient actively taking laxatives
 Patients still on oral vancomycin
for CDI
 Patient treated for CDI without
complete resolution of symptoms
with possible relapse
 Any patient with negative result in
past 7 days
 Asymptomatic patient for nursing
placement
 Patient near end of treatment (i.e.,
testing for cure)
Clostridium difficile Infection (CDI) Adult Treatment Algorithm
Treat with
vancomycin 125 mg
PO 4 times daily for
10-14 days
YES
Treat with
vancomycin
125mg PO
4 times daily for
10-14 days
May consider low
dose extension
therapy depending
on patient’s risk for
relapse
YES
Treat with
metronidazole
500 mg PO 3
times daily
for 10-14 days
NO
Discontinue
inciting antibiotic,
if possible
NO
Last reviewed/revised 08/2017
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
08/2017CCKM@uwhealth.org

C. Diff Infection
≥ 3 loose/liquid stools in previous 24 hours with risk factors
may also present low grade fever, mild abdominal pain
First
occurrence?
First
recurrence?
NO
Does pt have
severe disease?
YES
If treating, is pt
Intolerant/allergy
metronidazole or needs
alternative?
Refer to treatment for
second or further
recurrence
NO
YES
Consider Peds
Infectious Disease or
Peds Gastroenterology
consult
Is patient
candidate for
FMT?
Care and management
coordinated by Peds Infectious
Disease or Peds Gastroenterology
YES
Treat with metronidazole
30mg/kg/day enteral in
4 divided doses
(max 2000 mg/day)
Severe disease:
Treat with vancomycin 40mg/kg/day
enteral or rectal enema in
4 divided doses (max 2000 mg/day)
OR
Severe, complicated disease:
Vancomycin 40 mg/kg/day enteral
or rectal enema in 4 divided doses
(max dose 2000 mg/day)
PLUS
Metronidazole 30-40 mg/kg/day in
3 divided doses (max 2000 mg/day)
Consider alternative to metronidazole if:
Intolerant/allergic to metronidazole
Pregnant/breastfeeding
History of neuropathy
Cannot stop alcohol use during treatment
Pediatric CDI disease categories
Mild to Moderate disease: watery diarrhea without
systemic toxicity (mild abdominal pain and low-grade
fever may be present)
Severe disease: Evidence of systemic toxicity (e.g., high
grade fever, rigors); may be severe, complicated by
hypotension, shock, ileus; pseudomembranous colitis,
toxic megacolon
Note: Patients with underlying gastrointestinal disease
such as inflammabtory bowel disease or Hirschsprung’s
disease more likely to have severe disease
Clostridium difficile Infection (CDI) Pediatric Treatment Algorithm
Second or Further Recurrence Treatment
Vancomycin taper may be considered, especially under
consultation with Pediatric Infectios Disease and/or
Pediatric Gastroenterology.
Vancomycin Taper:
vancomycin 10 mg/kg 4 times daily for 10-14 days, then
vancomycin 10 mg/kg 2 times daily for 7 days, then
vancomycin 10 mg/kg once daily for 7 days, then
vancomycin 10 mg/kg every 2-3 days for 2-8 weeks
(max = 125 mg/dose).

Treat as clinically
indicated
Treat with
metronidazole
30 mg/kg/day
enterally in 4
divided doses
(max 2000mg/day)
Fecal microbiota therapy criteria:
Documented C Diff infection with stool test and
documented relapse despite appropriate treatment
(i.e., 3
rd
episode of CDI)
NOT currently completing a course of anti-infectives
(other than targeted CDI therapy with oral
vancomycin or oral metronidazole) for other
infectious conditions
Clinically stable in ambulatory setting
Treat with vancomycin 10mg/kg/dose
4 times a day for 10-14 days
(max 125 mg/dose)
Infection Control at Home counseling points:
Clean home with bleach
Wash hands with soap and water often
Designate bathroom for infected
household member
Launder linens/clothes with bleach in
warm/hot water
҉ Remember! Enhanced contact precautions if patient is
symptomatic and there’s CDI flag in chart! or high
suspicion of relapse within 90 days of last positive test
NO
Discontinue inciting
antibiotic, if possible
YES
NO
NO
YES
WHEN TO TEST PEDIATRIC PATIENTS
Patients ≥ 3 years:
Test if patient with diarrhea (≥ 3 unformed stools
from baseline bm/day in the previous 24 hours), with
risk factors and no alternative etiology for diarrhea
Patients < 36 months:
Consider alternative etiologies for diarrhea (e.g.,
antibiotic associated diarrhea)before testing
given high false-positive rate in younger
population.
TEST only if patient has appropriate clinical
findings ( ≥ 3 unformed stools from baseline bm/
day in the previous 24 hours) with additional
risk factors or,
Patient has appropriate clinical findings AND
concern of outbreak situation
TEST if patient < 1 year , has appropriate clinical
findings and in the presence Hirschsprung's
disease or other severe motility disorders
DO NOT TEST….
If patient actively taking laxatives
Patient still taking oral vancomycin
Patient treated with CDI without complete
resolution of symptoms for possible relapse
If patient has test result in past 7 days
Patient near end of treatment (i.e., testing for
cure)
Last reviewed/revised: 08/2017
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
08/2017CCKM@uwhealth.org

27


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