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C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager.

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Presentation on theme: "C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager."— Presentation transcript:

1 C. difficile in the Age of Antimicrobial Stewardship Darcy Whitlock, MS GI Disease Product Manager

2 Top 7 Threats to the Human Race 2 Source adapted from Science, Vol 325, September 2009 Available at

3 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 3 rd leading cause of death behind heart disease & cancer 2013: Infectious disease remains a critical concern as antimicrobial resistance increases 3

4 Inpatient Settings One in every three patients will receive two or more antibiotics in the course of their hospital stay Of the patients receiving antibiotics, three out of every four will receive unnecessary or redundant therapy, resulting in excessive use of antibiotics CDC – Get Smart Campaign 4

5 Outpatient Settings CDC – Get Smart Campaign Each year, tens of millions of antibiotics are prescribed unnecessarily for viral upper respiratory infections Antibiotic use in primary care is associated with antibiotic resistance at the individual patient level The presence of antibiotic-resistant bacteria is greatest during the month following a patients antibiotics use and may persist for up to 1 year 5

6 Improper Antimicrobial Use Longer duration than necessary Noninfectious/nonbacterial syndrome Treatment of colonization/ contamination 6 Unnecessary Necessary

7 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

8 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

9 Why Antimicrobial Stewardship? A balance of infection control and antibiotic management Achieve optimal clinical outcomes Decrease adverse drug events C. difficile Minimize development of antimicrobial resistance Preserve antimicrobial resources Reduce costs 9

10 Antimicrobial Stewardship Programs Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship – Core members include: – Infectious Disease Physician – Clinical Pharmacist – Clinical Microbiologist – Infection Control Professional – Information System Specialist 10

11 Simple Stewardship Solutions Treat only when necessary Use narrow-spectrum agents whenever possible Utilize rapid diagnostics Consider higher doses or shorter duration 11

12 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

13 Ideal Diagnostic Test A ffordable S ensitive (few false neg.) S pecific (few false pos.) U ser friendly R apid (30 min.) E quipment-free D eliverable 13 Mabey et al. Diagnostics for the Developing World. Nature Rev Microbiol 2004, 2:231-40

14 Antibiotic-Associated Diarrhea: Lifes a Beach with C. difficile Normal Gut FloraGut after Antibiotics C. diff finds a nice spotC. diff Infection 14 © JerryD via Flickr

15 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

16 C. difficile Economic Impact Several studies examine costs 16 Kyne, et al. Clin Infect Dis. 2002; 34: OBrien et al. Infect Control Hosp Epidemiol. 2008; 46: Dubberke, et al. Clin Infect Dis. 2008; 46:

17 Cycle of Antibiotics Primary Infection Antibiotic Treatment C. difficile Infection D/C primary antibiotics Start C. diff antibiotics 17

18 Gastrointestinal Disease: Impossible but True Impossible to diagnose on clinical symptoms alone, but frequently done Whats the primary symptom of any GI disease? 100s of causes, often treated empirically with antibiotics 18

19 Treat the Right Patients Lab tests are essential for proper diagnosis and to avoid empiric antibiotic treatment What if a test: – Doesnt actually tell if someone is sick – Takes so long for results the doctor has already treated the patient empirically 19

20 DNA = Cookbook; Gene = Recipe 20 Gene Product

21 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

22 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 doesnt always tell us whats happening – Doesnt indicate if gene is turned on producing toxin in the patient 22

23 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

24 What Test is Best? There is no optimal test for C. difficile Each method has advantages & drawbacks MethodAdvantageDrawback GDHSensitive detection, shows bacteria are present Doesnt say if C. difficile strain can produce toxin Toxin A/BIndicates active disease, Most clinically relevant Will not identify carriers, may not detect all positive patients MolecularSensitive detection of toxigenic bacteria Doesnt say if toxin is present, does not differentiate active disease 24

25 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

26 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

27 UK Guidelines 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 27 Planche, et al. Lancet Infectious Diseases. E-pub Sept. 3, 2013.

28 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%

29 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

30 Carrier Rates COMMON CARRIERSRATE Healthy Adults1 – 3% People with recent healthcare exposure15 – 25% Residents of Long Term Care Facilities % Newborn Infants % 30 Treating carriers is ineffective – Contributes to antibiotic overuse – Puts individual patient at risk of contracting CDI Identification important for infection prevention

31 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 Infection Control and Hospital Epidemiology. 29(11):

32 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

33 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

34 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

35 Infection Control Recommendations Cohort CDI patients C-III Isolation B-III Hand Hygiene A-II Contact Precautions A-I SHEA/IDSA Guidelines for C. difficile infection in adults ICHE 31(5) 35

36 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 contacts 2.Disinfect surfaces daily or after each use of the bathroom to prevent transmission 36 Thanks to Dr. Curtis Donskey, Case Western Reserve University, for this example

37 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

38 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

39 39

40 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.

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