Antimicrobial
Stewardship Initiatives
C Difficile Treatment
Deanne Tabb PharmD, MT (ASCP)
Infectious Disease Specialist
CALIFORNIA SENATE BILL NO. 1311 (JULY 1
ST
2015)
Existing law requires general acute care hospitals to develop a process for
evaluating the judicious use of antibiotics, the result of which is required to be
monitored by appropriate representatives and committees involved in quality
improvement activities.
• Adopt and implement an antimicrobial stewardship policy in accordance with
guidelines established by the federal government and professional
organizations. This policy shall include a process to evaluate the judicious
use of antibiotics in accordance with paragraph (3) of subdivision (a) of
Section 1288.8.
• Develop a physician supervised multidisciplinary antimicrobial stewardship
committee, subcommittee, or workgroup.
• Appoint to the physician supervised multidisciplinary antimicrobial
stewardship committee, subcommittee, or workgroup, at least one physician
or pharmacist who is knowledgeable about the subject of antimicrobial
stewardship through prior training or attendance at continuing education
programs, including programs offered by the federal Centers for Disease
Control and Prevention, the Society for Healthcare Epidemiology of America,
or similar recognized professional organizations.
• Report antimicrobial stewardship program activities to each appropriate
hospital committee undertaking clinical quality improvement activities.
TEAM MEMBERS
• Antimicrobial Stewardship Team: Infectious Disease physician (Chair), ID
pharmacist, Infection Control preventionist, Microbiology supervisor,
Hospitalist, and Intensivist
• LEAPT C. difficile Steering Committee: members from Clinical
Transformation, Quality Management, Nursing, Pharmacy, Infection Control,
Information Technology
• Senior Nursing leaders
• Unit nursing leadership
• Frontline clinical staff
• Risk Management
PROCESS
• Antimicrobial Stewardship Team (AST) website created
• Daily Activities include
- Assessment of use of restricted antimicrobial agents
- Pharmacokinetic management of antibiotics through TDM
- Microbial follow up for inpatients and ED patients
- Antibiogram development
- Order set, empiric guideline, and pathway development
- Assessments of intravenous (IV) to oral (PO) antibiotic
- Antimicrobial dose optimization program
GOALS
• Increase appropriate use of antimicrobials
• Increase the rate of Infectious Disease indications
accompanying physician orders for antimicrobials
CDI GOALS
• To use antimicrobial stewardship initiatives to
prevent Clostridium difficile colitis infections (CDI)
• Ensure appropriate treatment for C. difficile positive
patients
• Improve timely initiation of C. difficile contact
precautions
• Provide counseling and education to C. difficile
patients
BACKGROUND
• Clostridium difficile is a gram-positive anaerobe
• Considerable morbidity and mortality
• Ensuring timely identification of patients with C. difficile infection followed
by optimal treatment is important
• Established risk factors for the development of C. difficile include:
- Recent antibiotic use in the past 90 days
- Extended period in a healthcare facility
- Increased age (> 65)
- Serious underlying illness (immunocompromised receiving
chemotherapy)
- Use of proton pump inhibitor or H2 antagonist
SCOPE OF CDI PROJECT
• A dashboard was developed using a data extraction tool to evaluate the presence of any of
the following in patients concurrently identified with C. difficile infection:
•
Community acquired; healthcare facility related; nosocomial
•
Recurrent
•
Proton-pump inhibitor or H2 antagonist use
•
Exposure to chemotherapy
•
Severity of CDI illness
•
Appropriateness of C. difficile therapy
•
Discontinuation of concomitant offending antibiotics
•
Use of antiperistaltic agent
•
Previous exposure to clindamycin, cephalosporins, or fluoroquinolones
•
Exposure to three or more antibiotics
•
Durations of therapy beyond evidenced based recommendations
•
Antimicrobial selection was assessed and prescribers were contacted with alternative
recommendations outlined in the C. difficile clinical pathway
•
Recommendations to discontinue anti-motility agents were also performed to prevent
toxic mega colon
There are several
classification
systems taking into
account a variety
of severity markers
SEVERITY OF ILLNESS
Clostridium difficile Infection Guidelines for Severity Classification
IDSA Recommendation2
ACG Recommendation3
Mild/Moderate
Mild/Moderate
3
 WBC ≤ 15,000 cells/mm
 Diarrhea
AND
PLUS
 SCr < 1.5 x baseline
 Anything not meeting severe/complicated criteria
Severe
Severe
 WBC >15,000 cells/mm3
 Albumin < 3 g/dL
OR
PLUS
 SCr ≥ 1.5 x baseline
 WBC ≥ 15,000 cells/mm3
OR
 Abdominal tenderness
Severe Complicated
Severe Complicated
Any one of the following…
Any one of the following attributable symptoms…
 Hypotension/Shock
 Admission to ICU
 Ileus
 Hypotension
 Megacolon
 Fever ≥ 38ºC
 Ileus or Abdominal distension
 Altered mental status
 WBC ≥ 35,000 cells/mm3
 Serum lactate > 2.2 mmol/L
 End organ failure
CDI CLASSIFICATION AND
INITIAL TREATMENT PER IDSA
Classification
Definition
Treatment
Mild/Moderate
WBC ≤ 15,000 cells/mm3
AND
SCr < 1.5 x baseline
Metronidazole 500mg PO TID
Severe
WBC > 15,000 cells/mm3
OR
SCr ≥ 1.5 x baseline
Vancomycine 125mg PO QID
Severe
Complicated
Presence of Hypotension,
Vancomycin 500mg PO QID
Shock, Ileus, or Megacolon PLUS
Metronidazole 500mg IV TID
Duration of therapy10-14 days
Cohen SH, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society of Healthcare
Epidemiology of America (SHEA) and the Infectious Disease Society of America (IDSA). Infection Control and Hospital Epidemiology. 2010; 31: 432-450
INTERNAL EVALUATION
9 month retrospective chart review
• February - October 2014
• N = 63 patients
Internal Evaluation: Patient Demographics
N=63
%
N=63
%
18-64
28
Most Common Risk Factors Present in Past 90
days*
44% Fluroquinolones
21
33%
>/= 64
35
56% Other Antibiotics
Age3
No Antibiotics Prior to CDI
Diagnosis
Gender
21
33%
21
33%
32
51%
6
7
10%
11%
56
5
89%
11%
Male
30
48% PPIs
Female
31
52% H2-Antagonists
Chemotherapy
Infection
20
32% Episode At Time of Study Enrollment
Cardiac
Diabetes
6
3
Reasons for Hospitalization
10% First Episode
5% Recurrence
GI Complaints
27
43% Comorbidities Affecting Guideline Parameters
Other
19
30% End-Stage Renal Disease
Community Acquired
10
16%
Health-Facility Acquired
Nosocomial
33
20
52%
32%
Type of CDI
10
16%
RESULTS
• N = 63
45%
• Mild/moderate
• IDSA (43%)
• ACG (38%)
• Severe/Severe
Complicated
• Higher rate of Severe
Complicated classification
per ACG
• Positive Response on
monotherapy: 63%
Percent of Patients
40%
35%
30%
25%
20%
15%
10%
5%
0%
IDSA
ACG
Classification System
Mild/Mod
Severe
Severe Complicated
Combination Therapy
(Vancomycin + Metronidazole 500 mg IV TID)
N=12/20 (60%)
• Vancomycin 500mg
• N=1 (Resolved)
• Vancomycin 125-250mg
Positive Response N = 8 (75%)
Treatment Failure N = 3 (25%)
Vancomycin Doses Utilized to
Treat Severe Complicated C. diff
N=1
(8%)
N=4
(33%)
N=7
(58%)
Vancomycin 125mg
Vancomycin 250mg
Vancomycin 500mg
CONCLUSION
• ACG vs IDSA
• Equally predictive in distinguishing mild/moderate disease
versus severe
• ACG overestimates the incidence of severe complicated
• Severe complicated patients per ACG had clinical
resolution on monotherapy
• Compliance
• Utilization of the IDSA classification system is important to
ensure optimal therapy selection in patients with CDI
• Lack of guideline compliance leads to treatment failure
and extended length of stay for patients with CDI
FECAL MICROBIOTA TRANSPLANT
PROTOCOL
•
Fecal transplant should only be attempted in stable patients with a history of
multiple recurrence and no other options
•
Identify donor for transplant
•
Provide dietary instructions for patient
•
Obtain consent for transplant
•
Confirm route of administration with ordering physician
•
Coordinate consult with GI and endoscopy
•
Calculate when patient’s CDI treatment will be completed
•
Patient will need to be finished with antibiotics for 24-72 hours before
transplant
SCREENING STOOL DONORS
•
A preferred stool donor is an individual who has had intimate physical contact
with the patient (spouse or significant partner)
•
Stool donors are screened for evidence of previous exposure to contagious
infectious agents which include:
Toxin A or Toxin B of Clostridium difficile
Disease causing bacteria and parasites
Hepatitis A, B, and C viruses
HIV-1, HIV-2
Syphilis
•
Stool donor must be antibiotic naïve for past 90 days
PATIENT
 Stop all antibiotics 1-3 days prior to transplantation
 For NG tube/EGD administration:
 Administer pantoprazole 20 mg orally the evening before and the morning of
procedure (if not already receiving a proton pump inhibitor)
 For enema or colonoscopy administration:
 May consider Golytely bowel preparation on the evening prior to transplant (discuss
with GI consultant prior to scheduling procedure)
STOOL PROCESSING
•
Obtain fresh stool sample (collection
to administration should not exceed 6
hours)
•
Weigh amount of stool needed for
procedure (see dose below) then place
measured amount in single use
household blender i.e., neutrabullet or
Bella blender. Add specified amount
of normal saline based on site of
administration listed below. Blend for
2-4 minutes under the microbiology
biologic hood until sample is
homogenized.
•
Filter the suspension using sterile
four-by-four (secure with thick rubber
band) or screen filter. Allow adequate
time for slow filtration.
•
Discard blender, remaining filtrate,
and any utensils used in preparation
in a biohazard container
NG TUBE/EGD
 Cure rate: 76% (due to the impact of gastric acidity; ensure basic environment with PPI
before administration)
 Dose: 5 - 30 g of stool. Compound approximately 200 grams of stool in 250 mL of
sterile normal saline for a final concentration of 0.8 grams/mL, filter, then draw up 25
mL (final dose 20 grams) in 60 mL Slip Tip syringe (EGD scope compatible syringe),
clean outside tip of syringe and cap. Label (same requirements as medication) sample
and deliver immediately for administration.
 For NG tube administration: draw up 25 mL of filtrate into Luer lock syringe and cap
 Advantage: appropriate for pediatric population
 Disadvantage: potential degradation of the stool sample by gastric, pancreatic, or
biliary enzymes.
COLONOSCOPY
 Cure rate: 96.3%
 Dose: 50 g of stool in 200 mL of normal saline for a final concentration of 0.25
grams/mL, filter, then transfer 120 mL of suspension into two 60 mL Slip Tip syringes
(colonoscope compatible syringe). Label sample and deliver immediately for
administration.
 Advantage: visualization of affected mucosa and ability to administer fecal transplant
directly to site. Additionally the area can be inspected for any complications related to
the infection.
 Disadvantage: perforation especially in patients with fulminant toxic megacolon.
ENEMA
 Cure rate: 88% to 95.4%
 Dose: 50 -150 g of stool in 200
mL of normal saline
 For enema: instill designated
amount into rectal retention
enema bulb, label sample and
deliver for immediate nurse
administration
 Advantage: appropriate for
patients with fulminant toxic
megacolon (when compared to
colonoscopy)
 Disadvantage: retrograde
leakage, and may require a
series of enemas
POST-PROCEDURE
• Avoid the excretion of donated stool for > 4 hours
• Post-transplant, bed rest as long as possible until next day
• Follow Pre/Post dietary instructions
• Patient should call provider if any signs of C. difficile infection
return
WHAT TO EAT BEFORE FMT
 Two weeks prior to the transplant eat a low fiber diet (fiber
feeds microbiota, so a low fiber diet will starve the bad
microbiota)
 Learn what foods work best for you. Avoid foods that will trigger
diarrhea. This will be important before and after the fecal
transplant.
 Eat unprocessed food and minimize gut stressors like
processed food, gluten, sugar and alcohol.
WHAT TO EAT AFTER FMT
 Probiotics are not necessary. They may upset the new flora.
The fecal transplant is the Ultimate Probiotic
 Don’t risk experimenting with a new diet
 Eat a high fiber diet for at least 3 months after fecal transplant
fruits (raspberries, apples, bananas, raisins), grains (bran,
barley, brown rice, oatmeal), legumes, nuts, seeds (lentils,
baked beans, almonds)
 Fermented food, encourages growth of the good microbiota.
yogurt with “active cultures,” cottage cheese, whey, kefir,
pickled foods (pickles, beets, radish), Korean kimchi,
sauerkraut, tempeh
PRESCRIBER EDUCATION
• Stage severity of CDI and select appropriate therapy
outlined in CDI algorithm (based on IDSA guidelines)
Oasis  Antimicrobial Stewardship  Infectious Diseases 
C. difficile folder  C. difficile Treatment Pathway
• Minimize Risk Factors associated with CDI
• Limit the use of Fluoroquinolones and proton pump inhibitors
when possible
• Symptomatic improvement Expected within 96 hours of
treatment initiation
• May consider consultation with Gastroenterology, Infectious
Diseases or surgery as needed
ANTIMICROBIAL STEWARDSHIP
• Use antibiotics judiciously
•
Select appropriate empiric therapy (Empiric guidelines
available on AST website On Oasis under Medical)
•
Please write ID indication in order when prescribing antibiotics
or select indication in CPOE.
•
Notify Dr. Tabb, ID pharmacist at #1420 to add additional
indications in CPOE)
•
Reevaluate the need for antibiotics at the 72-hour mark
•
Streamline therapy once microbiology data available
•
Set antibiotic duration of therapy
Questions