c. difficile in the age of antimicrobial stewardship darcy whitlock, ms gi disease product manager
TRANSCRIPT
![Page 1: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/1.jpg)
C. difficile in the Age of Antimicrobial Stewardship
Darcy Whitlock, MSGI Disease Product Manager
![Page 2: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/2.jpg)
Top 7 Threats to the Human Race
2Source adapted from Science, Vol 325, September 2009Available at http://www.sciencemag.org/content/325/5948.cover-expansion
![Page 3: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/3.jpg)
Infectious Disease & Antibiotics
• 1970: Surgeon General William Stewart said the US was “ready to close the book on infectious disease as a major health threat”– Modern antibiotics, vaccination, and sanitation
methods had done the job
• 1995: Infectious disease is the 3rd leading cause of death behind heart disease & cancer
• 2013: Infectious disease remains a critical concern as antimicrobial resistance increases
3
![Page 4: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/4.jpg)
Inpatient Settings
CDC – Get Smart Campaign 4
![Page 5: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/5.jpg)
Outpatient Settings
CDC – Get Smart Campaign 5
![Page 6: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/6.jpg)
Improper Antimicrobial Use
• Longer duration than necessary• Noninfectious/nonbacterial
syndrome• Treatment of colonization/
contamination
6
Unnecessary
Necessary
![Page 7: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/7.jpg)
Costs of Antibiotic Resistance
• Antibiotic resistance increases the economic burden on the entire US healthcare system– Resistant infections cost more to treat and can prolong
healthcare use
• More than $1.1 billion is spent annually on unnecessary antibiotic prescriptions for respiratory infections in adults
• In total, antibiotic resistance is responsible for:– $20 billion in excess healthcare costs– $35 billion in societal costs– 8 million additional hospital days
CDC – Get Smart Campaign 7
![Page 8: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/8.jpg)
“Every antibiotic expected by a patient, every unnecessary prescription written by a doctor,
every uncompleted course of antibiotics is potentially signing a death warrant for a future
patient.”
Dryden, et al. 20098
![Page 9: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/9.jpg)
Why Antimicrobial Stewardship?
• A balance of infection control and antibiotic management
Achieve optimal clinical outcomesDecrease adverse drug events• C. difficile
Minimize development of antimicrobial resistancePreserve antimicrobial resourcesReduce costs
9
![Page 10: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/10.jpg)
Antimicrobial Stewardship Programs
• Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship – 2006http://www.idsociety.org
• Core members include:–Infectious Disease Physician–Clinical Pharmacist–Clinical Microbiologist–Infection Control Professional–Information System Specialist
10
![Page 11: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/11.jpg)
Simple Stewardship Solutions
• Treat only when necessary• Use narrow-spectrum agents whenever possible• Utilize rapid diagnostics• Consider higher doses or shorter duration
11
![Page 12: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/12.jpg)
Rapid Diagnostics
• Test, Target, Treat– Know the organism, know the appropriate treatment
• Reduce antibiotic overuse & unwanted side effects• Shorten time to appropriate therapy• Targeted therapy improves pharmacy savings• Reduced infection transmission increases infection
control savings
12
![Page 13: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/13.jpg)
Ideal Diagnostic Test
Affordable
Sensitive (few false neg.)
Specific (few false pos.)
User friendly
Rapid (30 min.)
Equipment-free
Deliverable
13
Mabey et al. Diagnostics for the Developing World. Nature Rev Microbiol 2004, 2:231-40
![Page 14: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/14.jpg)
Antibiotic-Associated Diarrhea: Life’s a Beach with C. difficile
Normal Gut Flora Gut after Antibiotics
C. diff finds a nice spot C. diff Infection
14© JerryD via Flickr
![Page 15: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/15.jpg)
Risk Factors for C. difficile
• Previous antibiotic exposure– Some cases unrelated to antibiotics
• Disruption to intestinal flora• Advanced age• Hospitalization– Community acquisition becoming more common
• Pregnancy
15
![Page 16: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/16.jpg)
C. difficile Economic Impact
• Several studies examine costs
16
Kyne, et al. Clin Infect Dis. 2002; 34: 346-353.O’Brien et al. Infect Control Hosp Epidemiol. 2008; 46: 497-504.Dubberke, et al. Clin Infect Dis. 2008; 46: 497-504.
![Page 17: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/17.jpg)
Cycle of Antibiotics
17
![Page 18: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/18.jpg)
Gastrointestinal Disease:Impossible but True
• Impossible to diagnose on clinical symptoms alone, but frequently done
• What’s the primary symptom of any GI disease?
• 100s of causes, often treated empirically with antibiotics
18
![Page 19: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/19.jpg)
Treat the Right Patients
• Lab tests are essential for proper diagnosis and to avoid empiric antibiotic treatment
• What if a test:– Doesn’t actually tell if someone is sick– Takes so long for results the doctor has already treated the
patient empirically
19
![Page 20: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/20.jpg)
DNA = Cookbook; Gene = Recipe
20
Gene Product
![Page 21: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/21.jpg)
C. difficile Toxins A&B• Toxins cause the disease symptoms• Toxin results most closely correlate to disease state
and clinical outcome– Not all toxin assays perform equally
• Toxins produced only when needed by the bacteria– Typically in response to nutritional or environmental stress
21
![Page 22: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/22.jpg)
Molecular Testing• Nucleic Acid Amplification Tests (NAAT)– DNA test, PCR, LAMP, isothermal NAT
• Detects the gene (DNA) that encodes for toxin• Great for sensitive identification,but doesn’t always tell us what’s happening– Doesn’t indicate if gene is turned on producing toxin in the patient
22
![Page 23: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/23.jpg)
C. difficile GDH Antigen• Glutamate dehydrogenase (GDH) produced in
large amounts by all C. difficile bacteria• GDH shows C. difficile is present & growing– Very sensitive detection of bacteria
• Does not indicate if they produce toxin, need follow-up test for toxin
23
![Page 24: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/24.jpg)
What Test is Best?• There is no optimal test for C. difficile• Each method has advantages & drawbacks
Method Advantage Drawback
GDH Sensitive detection, shows bacteria are present
Doesn’t say if C. difficile strain can produce toxin
Toxin A/B Indicates active disease,Most clinically relevant
Will not identify carriers, may not detect all positive patients
Molecular Sensitive detection of toxigenic bacteria
Doesn’t say if toxin is present, does not differentiate active disease
24
![Page 25: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/25.jpg)
Guidelines: Points All in Agreement
• Toxin A/B testing should not be used as a stand-alone test
• GDH screening prior to toxin testing is recommended for improved sensitivity
• Repeat testing (C. diff x 3) not helpful and should be discouraged when using more sensitive testing methods (GDH or molecular)
25
![Page 26: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/26.jpg)
Molecular Testing Disagreement
• ASM: Molecular can be used stand-alone or as confirmation of rapid results
• SHEA/IDSA: PCR has high sensitivity & specificity, looks promising, but not enough data yet to recommend
• UK: PCR is a good screening test, but not specific for active disease– Follow up with sensitive toxin test for clinical activity
26
![Page 27: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/27.jpg)
UK Guidelines - 2012
• Largest most comprehensive study ever done• 12,441 samples compared to patient clinical
features & outcomes• GDH, Toxin, NAAT, Cytotoxicity, Toxigenic Culture• Testing for active toxin production is critical for
determining disease state & clinical outcome
Webinar by Dr. Mark Wilcox, co-author of the UK study & Guidelines available @ http://www.whitehatcom.com/alere
27Planche, et al. Lancet Infectious Diseases. E-pub Sept. 3, 2013.
![Page 28: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/28.jpg)
C. difficile Testing Algorithm
Positive for toxigenic C. difficile
Positive GDH Antigen and Negative Toxin
Negative for toxigenic C. difficile
•Reporting Results •Additional
Testing
75 – 80%
10%
10-15%
28
NPV 99.8%
![Page 29: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/29.jpg)
What Does GDH + , Toxin – Mean?
• C. difficile bacteria are present but toxin is not detected
• Could be due to:– Colonization with a nontoxigenic strain– Patient is a carrier of a toxigenic strain– Toxin level is below the limit of detection
• UK Study: GDH+, Tox- patients have similar outcomes to C. diff negative patients
29
![Page 30: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/30.jpg)
Carrier Rates
COMMON CARRIERS RATEHealthy Adults 1 – 3%People with recent healthcare exposure 15 – 25%Residents of Long Term Care Facilities 20 - 51%Newborn Infants 50 - 70%
30
• Treating carriers is ineffective – Contributes to antibiotic overuse– Puts individual patient at risk of contracting CDI
• Identification important for infection prevention
![Page 31: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/31.jpg)
Antimicrobial Stewardship Directly Impacts C. difficile Rates
31
• AMS program instituted at VAMC Houston– Required ID Doc approval for most antibiotics
• C. difficile infection rate dropped 42% solely from restricting inappropriate antibiotics
• Study presented at ID Week, 2013– 10% reduction in antibiotics = 17% reduction in C. diff rate– Penicillins and β-lactams had most effect– Fluoroquinolone decrease had surprisingly small effect
Nuila, et al. 2008. Infection Control and Hospital Epidemiology. 29(11): 1096-97
![Page 32: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/32.jpg)
C. difficile Testing Companion
Likely active infection Likely not active infection– Carrier, colonized
32
• C. difficile toxins typically cause inflammation• Lactoferrin results can help differentiate carriers
from active infections
![Page 33: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/33.jpg)
Fecal WBC Smear
• False negatives from cell breakdown– Need intact cells for microscopic identification– WBCs break down rapidly in stool• Digestive enzymes, cytotoxins
• Variation from different users, different prep techniques, number of fields examined
33
![Page 34: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/34.jpg)
WBC Testing Options - Lactoferrin
• Highly accurate marker of WBCs (neutrophils/PMNs)• Elevated lactoferrin = WBCs are present, inflammation
in GI tract• Stable marker of WBCs– Unaffected by cell breakdown
• Non-subjective, no variation between users
34
![Page 35: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/35.jpg)
Infection Control Recommendations
SHEA/IDSA Guidelines for C. difficile infection in adults. 2010 ICHE 31(5) 35
![Page 36: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/36.jpg)
Importance of Daily Cleaning
• Elderly relative living with you develops infectious diarrhea
• Your young children have daily contact with their ill grandparent
• Do you:1. Wait 10 days until the illness has resolved before cleaning
the bathroom & other objects the person contacts2. Disinfect surfaces daily or after each use of the bathroom
to prevent transmission
36Thanks to Dr. Curtis Donskey, Case Western Reserve University, for this example
![Page 37: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/37.jpg)
Points to Remember• C. difficile testing is complex– No One & Done solution– High carrier rate can complicate treatment and
infection prevention decisions– Inflammation testing can aid diagnosis
37
![Page 38: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/38.jpg)
Points to Remember
• Proper rapid diagnosis of C. diff disease:– Improves patient outcomes– Prevent antibiotic overuse– Protect vulnerable patients from antibiotic-related
complications
• Antimicrobial stewardship plays a direct role in reducing C. difficile rates
38
![Page 39: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/39.jpg)
39
![Page 40: C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager](https://reader033.vdocument.in/reader033/viewer/2022061305/551437c3550346ec488b62b1/html5/thumbnails/40.jpg)
40
© 2013 Alere. All rights reserved.The Alere Logo and Alere are trademarks of the Alere group of companies.C. DIFF QUIK CHEK COMPLETE is a trademark of TECHLAB®, Inc. under license.