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Best though and continuous study Jerome Groopman

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Best though and continuous study Jerome Groopman Peter Gilligan Professor, Pathology-Lab Medicine UNC School of Medicine * * – PowerPoint PPT presentation

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Title: Best though and continuous study Jerome Groopman


1
Best though and continuous studyJerome Groopman
  • Peter Gilligan
  • Professor, Pathology-Lab Medicine
  • UNC School of Medicine

2
How I became a clinical microbiologist
  • Obtained doctoral degree in microbiology at the
    University of Kansas
  • Did post-doctoral training (2 years) in medical
    and public health microbiology at UNC Hospitals
  • Director of Microbiology Labs at St Christophers
    Hospital for Children (Philadelphia) for 4 years
  • Past 25 years, Associate Director then Director
    of the Clinical Microbiology-Immunology Labs at
    UNC Hospitals

3
What do clinical microbiologists do?
  • We serve
  • our patients
  • our health care-providing colleagues, physicians,
    nurses, physician assistants, pharmacy colleagues
  • hospital administrators
  • We make money for the institution
  • general public by insuring the public health
  • Involved in studying outbreaks of several
    emerging infectious diseases including current
    fungal meningitis one
  • will tell you about an emerging pathogens today-
    Clostridium difficile

4
How do we serve?
  • central role in the diagnosis and management of
    infectious diseases
  • central role in infection prevention and
    antimicrobial use
  • recognize emerging disease threats and outbreaks
    including bioterrorism events
  • we educate train health care providers
  • we create new knowledge (research) to deal with
    practical problems

5
Best things about my job
  • Direct impact on patient care and public health
    of the community
  • Intellectually challenging job requiring a broad
    fund of knowledge-need to know a little about a
    lot of things I am never bored!!!!!!!
  • Get to work with cutting edge technology
  • Work with highly motivated and intelligent
    individuals
  • Get to be at the cutting edge of infectious
    disease diagnosis
  • I am involved in global issues as they relate to
    infectious diseases

6
Worst things about my job
  • Incredible amounts of governmental oversight
  • Increasing emphasis on financial aspects of the
    job
  • Declining talent pool of technologists-THIS A
    GREAT JOB MARKET FOR YOU WITH APPROPRIATE
    TRAINING
  • Too much travel
  • Need to be responsible for an organization that
    run 24/7/365-we never close. Personally have
    worked through ice storms, blizzards, and
    hurricanes.

7
How you can become a clinical microbiologist
  • CLS programs available here, ECU, WSSU, Wake
    Forest, UNC-CH
  • Education is also available on line
  • 2 more years of school to get a BS in CLS
  • There is no unemployment in this group
  • Take ASCP certification exam to become certified
    as a MT.
  • Starting salary is 41,000 and up
  • Career options are amazingly diverse many former
    UNC students work in leadership positions in the
    pharmaceutical and biotech industries- Also have
    5 former employees currently in Med, Grad,
    Pharmacy School

8
Emerging Infectious Diseases in the Past 35 Years
  • Clostridium difficile
  • Ebola virus
  • novel H1N1 influenza AHIV
  • SARS and MERS CoV
  • Cryptosporidium
  • E. coli O157H7
  • Nipah virus
  • nv Creutzfeldt-Jakob disease
  • Sin Nombre Virus
  • West Nile Virus
  • Vibrio vulnificus
  • Cyclospora
  • Bacillus anthracis (BT agent)
  • CA-ORSA
  • TSST-1 S. aureus
  • XDR- and MDR-TB
  • MDR- pneumococcus
  • MDR-Acinetobacter
  • Rapidly growing mycobacterium
  • Rotavirus
  • Norovirus
  • BK virus
  • Chlamydophila pneumoniae
  • Penicillium marneffei
  • Legionella
  • Burkholderia cepacia complex
  • Burkholderia gladioli
  • VRE/VRSA
  • Helicobacter pylori
  • HHV-6
  • HPV
  • HCV
  • Avian influenza (H5N1)
  • Ehrlichia chaffenesis
  • Borrelia burgdorferi (Lyme disease)
  • Enterotoxigenic E. coli
  • Enteroadherent E. coli
  • Bordetella avium

9
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10
Clostridium difficile
  • General characteristics
  • Gram positive rod
  • Spore former
  • Anaerobic
  • Can be part of human microflora
  • Pathogenicity due to the production of two
    protein exotoxins A and B

11
Chance favors only the prepared mind
  • Louis Pasteur

12
Key events in the discovery of C. difficile
  • Larson and colleagues describe a toxin in the
    feces of a child with pseudomembranous colitis
    (1977)
  • Bartlett and colleagues show that C difficile can
    induce colitis in hamsters given clindamycin and
    then a variety of antibiotics and then proves
    that the organism can cause the same disease in
    humans (1978)
  • Serendipity is important- showed that C.
    sordellii antitoxin could neutralize toxins
    produced by C. difficile in a tissue culture
    cytotoxicity assay.

13
Key events in the discovery of C. difficile
  • Among others, Gilligan and colleagues show that
    C. difficile is the most common bacterial agent
    in a general population (1980)
  • Lyerly and colleagues purify two toxins, A and B,
    from C. difficile and also produce an important
    anti-toxin against these organisms (1982)

14
US deaths due to C. difficle has increased 2.3X
since 2000 mortality 4 Peery et al, 2012
Gastroenterology (in press)
Nature Reviews Gastroenterology Hepatology 8,
17-26 (January 2011)
15
What makes C difficile an important pathogen in
the industrialized world?
  • Important ideas
  • Organism can survive in the environment for
    months as spores spores are refractory to
    disinfectants especially alcohol and all
    antimicrobials
  • Alternation in the gut flora is important in
    predisposing patients to disease with this
    organism- antibiotics mediate this change
  • Microbiome is less diverse
  • Most common diarrheal disease etiology in the
    industrialized world requiring specific
    antimicrobial interventions
  • Leading health care associated pathogen in US

16
Age related C. difficile incidence in US
17
What factors has resulted in the re-emergence of
Clostridium difficile??
  • Emergence of highly virulent strains
  • Better case ascertainment
  • Improvement in lab diagnosis
  • Aging population
  • Decline in Bifidobacterium with age, an organism
    important in colonization resistance, in gut
    flora may create more permissive environment for
    C. difficile
  • Increased use of antimicrobials especially
    fluoroquinolones with anti-anaerobic activity to
    which C. difficile is resistant
  • This is being debated in the infectious disease
    community
  • 90 of C. difficile isolates are fluoroquinolone
    resistant

18
Why are antimicrobials an important risk factor
in C. difficile?
  • The vast majority of patients have received
    antimicrobials that alter the microbiome reducing
    its complexity and leading to C. difficile
    germination, growth and toxin production
  • Key protective organisms include Bacteriodes,
    Ruminococcus, Eubacterium, Lachnospira,
    Porphyromonadaceae)
  • Petrof et al 2013 Microbiome 13 Schubert et al.
    mBio 2014 5(3) e01021-14

19
Taur and Pamer 2014. Nature Medicine 20246-7
20
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21
Clostridium difficile PMC and toxic megacolon
22
C. difficile Spectrum of disease
  • Asymptomatic carriage
  • Mild diarrhea
  • Profuse diarrhea with non-specific colitis
  • Pseudomembranous colitis
  • Toxic megacolon

frequency
23
Rules for C. difficile testing
  • If the stick stands, the test is banned (type
    1-5)
  • High carriage rate in patients on antimicrobials
  • If the stick falls, test them all. (type 6 7)
  • Dr. Stephen Brecher

24
Report as negative for C. difficile
Report as positive for C. difficile Based on data
in literature of PVP gt95 for CDI
If NAAT for C. difficile toxin gene is positive,
report as positive for C. difficile. If NAAT for
C. difficile toxin gene is negative, report as
negative as C. difficile
25
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26
UNC C. difficile rates for the first quarter 2014
UNC infection rate is higher than for all NC
hospitals but not for ones of our size/complexity
27
Post-analytical phase-what test best predicts
disease
  • Large study of gt6000 disease episodes
  • Toxin positive patients had the highest mortality
  • Toxin positive and PCR positive patients had
    increased length of stay compared to PCR negative
    patients (Lancet, 2013 13936-45)
  • Toxin positive specimens have lower PCR Ct than
    NAAT only suggesting higher organism load in
    toxin positive patients (J. Hosp. Infect, 2013
    84311-5)

28
How do we interpret our test results based on
these data
  • GDH negative- no C. difficile (82.4)
  • GDH positive/PCR negative- no C. difficile (5.2)
  • GDH positive/PCR positive- C. difficile infection
    vs. excretor (7.9)
  • GDH positive/toxin positive- C. difficile
    infection (4.4)

29
What does C. difficile execretormean?
  • Likely be a clinical decision with infection
    prevention ramifications
  • Bottom line Need to treat the patient not the
    laboratory test

30
Fecal Microbial Transplant (FMT)
  • C. difficile recurrence rates are estimated to be
    20 to 30
  • Patients may have multiple recurrences that are
    increasingly refractory to antimicrobial therapy
  • Random controlled trial of FMT showed a
    resolution in 81 of patients after one infusion
    and resolution in an additional 2/3 after 2nd
    infusion antimicrobial therapy was effective in
    30
  • Study stopped early by data safety monitoring
    board (NEJM 2013 368407-15)

31
van Nood E et al. N Engl J Med 2013368407-415.
Microbiota Diversity in Fecal Microbiome
Transplants after Infusion of Donor Feces, as
Compared with Diversity in Healthy Donors.
32
FMT Donor issues
  • Stool vs stool substitute
  • Stool substitute-33 isolates recovered from the
    stool of healthy female-
  • 2 patients studied-both resolved diarrhea within
    72 hours (Microbiome 2013, 13)
  • FDA would prefer the stool substitute because of
    safety concerns which arise from using fecal
    specimens-
  • Advocates for FMT-think of it as an organ
    transplant
  • FMT-very expensive because of donor screening
  • Short-term FMT data excellent-90 success rate
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