Antimicrobial Stewardship Initiatives

C Difficile Treatment

Deanne Tabb PharmD, MT (ASCP)Infectious Disease Specialist

CALIFORNIA SENATE BILL NO. 1311 (JULY 1ST 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 ILLNESSClostridium difficile Infection Guidelines for Severity Classification

IDSA Recommendation2 ACG Recommendation3

Mild/Moderate WBC ≤ 15,000 cells/mm3

AND SCr < 1.5 x baseline

Mild/Moderate Diarrhea

PLUS Anything not meeting severe/complicated

criteriaSevere WBC >15,000 cells/mm3

OR SCr ≥ 1.5 x baseline

Severe Albumin < 3 g/dL

PLUS WBC ≥ 15,000 cells/mm3

OR Abdominal tenderness

Severe ComplicatedAny one of the following… Hypotension/Shock Ileus Megacolon

Severe ComplicatedAny one of the following attributable symptoms… Admission to ICU Hypotension 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

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

Classification Definition Treatment

Mild/Moderate WBC ≤ 15,000 cells/mm3

ANDSCr < 1.5 x baseline

Metronidazole 500mg PO TID

Severe WBC > 15,000 cells/mm3

ORSCr ≥ 1.5 x baseline

Vancomycine 125mg PO QID

Severe Complicated

Presence of Hypotension, Shock, Ileus, or Megacolon

Vancomycin 500mg PO QID PLUSMetronidazole 500mg IV TID

Duration of therapy10-14 days

INTERNAL EVALUATION

9 month retrospective chart review• February - October 2014• N = 63 patients

Internal Evaluation: Patient Demographics

N=63 % N=63 %

Age3

Most Common Risk Factors Present in Past 90 days*

18-64 28 44% Fluroquinolones 21 33%

>/= 64 35 56% Other Antibiotics 21 33%

GenderNo Antibiotics Prior to CDI Diagnosis 21 33%

Male 30 48% PPIs 32 51%

Female 31 52% H2-Antagonists 6 10%

Reasons for Hospitalization Chemotherapy 7 11%

Infection 20 32% Episode At Time of Study Enrollment

Cardiac 6 10% First Episode 56 89%

Diabetes 3 5%Recurrence 5 11%

GI Complaints 27 43% Comorbidities Affecting Guideline Parameters

Other 19 30% End-Stage Renal Disease 10 16%

Type of CDI

Community Acquired 10 16%

Health-Facility Acquired 33 52%Nosocomial 20 32%

RESULTS

• N = 63

• Mild/moderate• IDSA (43%)

• ACG (38%)

• Severe/Severe Complicated• Higher rate of Severe

Complicated classification per ACG

• Positive Response on monotherapy: 63%

IDSA ACG0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Mild/Mod Severe Severe Complicated

Classification System

Per

cen

t of

Pat

ien

ts

Combination Therapy (Vancomycin + Metronidazole 500 mg IV TID)

N=12/20 (60%)

• Vancomycin 500mg• N=1 (Resolved)

• Vancomycin 125-250mgPositive Response N = 8 (75%)

Treatment Failure N = 3 (25%)

N=7 (58%)

N=4 (33%)

N=1 (8%)

Vancomycin Doses Utilized to Treat Severe Complicated C. diff

Vancomycin 125mg Vancomycin 250mgVancomycin 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 difficileDisease causing bacteria and parasitesHepatitis A, B, and C virusesHIV-1, HIV-2Syphilis

• 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)

• 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

STOOL PROCESSING

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.

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

ENEMA

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