Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Leptospirosis wikipedia , lookup
Gastroenteritis wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Schistosomiasis wikipedia , lookup
Eradication of infectious diseases wikipedia , lookup
Oesophagostomum wikipedia , lookup
Marburg virus disease wikipedia , lookup
Middle East respiratory syndrome wikipedia , lookup
Best thought and continuous study Jerome Groopman Peter Gilligan Professor, Pathology-Lab Medicine UNC School of Medicine 5/4/2017 1 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 Christopher’s Hospital for Children (Philadelphia) for 4 years • Past 31 years, Associate Director then Director of the Clinical Microbiology-Immunology Labs at UNC Hospitals 5/4/2017 2 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 preparing for potential outbreaks of several emerging infectious diseases including MERS-CoV, Ebola, and H5N2 avian influenza, MDR-organisms • will focus on the most important Health Care Associated pathogen- Clostridium difficile 5/4/2017 3 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 5/4/2017 4 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 used for infectious disease diagnosis • Work with highly motivated and intelligent individuals • I am involved in global issues as they relate to infectious diseases 5/4/2017 5 Worst things about my job • Incredible amounts of governmental oversight » It is increasing • Increasing emphasis on financial aspects of the job » Less time for science-more involvement in systems management • Declining talent pool of technologists-THIS A GREAT JOB MARKET FOR YOU WITH APPROPRIATE TRAINING • Need to be responsible for an organization that run 24/7/365-we never close. Personally have worked through ice storms, blizzards, and hurricanes. 5/4/2017 6 How you can become a clinical microbiologist • CLS programs available here, ECU, WSSU » 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 42,000 and up » Career options are amazingly diverse; many former UNC students work in leadership positions in the pharmaceutical, diagnostic and biotech industries- Also have 5 former employees currently in or recently graduated from Med, 5/4/2017Grad and Pharmacy School 7 Emerging Infectious Diseases in the Past 35 Years • Clostridium difficile*# • Ebola virus • novel H1N1 influenza AHIV*# • SARS and MERS CoV* • Cryptosporidium* • E. coli O157:H7*# • 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*# • Campylobacter*# •5/4/2017 ESBL-Enterobactericeae* • • • • • • • • • • • • • • • • • • • • 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 Microsporidium* 8 The concept of “One Health” Interface of disease among humans, domestic and wild animals driven by ecologic, socieconomic and climatic factors Ex. Influenza H5N1 and MERS-CoV Gebreyes et al PLOS Negl. Trop. Dis. 2014, 8:e3257 Why do we care about diseases in domestic animals? Why do we care about diseases in domestic animals? We annually raise 21 billion animals for food We live in close proximity to them Gebreyes et al. PLOS Neg. Trop. Dis. 2014, 8:e3257 One Health 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 Chance favors only the prepared mind Louis Pasteur 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. 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) 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) 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 patient’s 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 Age related C. difficile incidence in US What factors has resulted in the reemergence 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 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 1:3: Schubert et al. mBio 2014 5(3): e01021-14 Taur and Pamer 2014. Nature Medicine Clostridium difficile PMC and toxic megacolon C. difficile: Spectrum of disease Asymptomatic carriage Mild diarrhea Profuse diarrhea with non-specific colitis Pseudomembranous colitis Toxic megacolon frequency Rules for C. difficile testing • If the stick stands, the test is banned (type 15) » High carriage rate in patients on antimicrobials • If the stick falls, test them all. (type 6 + 7) Dr. Stephen Brecher 5/4/2017 28 Report as positive for C. difficile Report as negative for C. difficile Based on data in literature of PVP >95% 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 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 Post-analytical phase-what test best predicts disease • Large study of >6000 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; 13:936-45) • Toxin positive specimens have lower PCR Ct than NAAT only suggesting higher organism load in toxin positive patients (J. Hosp. Infect, 2013; 84:311-5) 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%) What does “C. difficile execretor” mean? Likely be a clinical decision with infection prevention ramifications Bottom line: Need to treat the patient not the laboratory test 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 2013; 368:407-15) (NEJM Fecal Microbiome Transplants Microbiota Diversity in after Infusion of Donor Feces, as Compared with Diversity in Healthy Donors. van Nood E et al. N Engl J Med 2013;368:407-415. 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, 1:3) • 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