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Bugs in the Belly- Some are good, some are bad

Bugs in the Belly- Some are good, some are bad. Mark H. Mellow, MD INTEGRIS Digestive Health Center 405-713-4430. Normal gut bacteria are FRIENDLY - They not only don’t cause disease, they prevent and fight off disease. We know very little about our friendly bacteria.

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Bugs in the Belly- Some are good, some are bad

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  1. Bugs in the Belly-Some are good, some are bad Mark H. Mellow, MD INTEGRIS Digestive Health Center 405-713-4430

  2. Normal gut bacteria are FRIENDLY - They not only don’t cause disease, they prevent and fight off disease

  3. We know very little about our friendly bacteria • We have always relied on culturing techniques to identify bacteria • Over 80% of friendly bacteria cannot be cultured. New “hi-tech” method- DNA sequencing

  4. Expect an explosion of info on gut bacteria in the next 20 years

  5. Bug Facts We have 10-1000 x as many bacterial cells in our bodies than we have our own cells

  6. The Gastrointestinal tract has most of our bacteria- 10-100 trillion bacteria1,000,000,000,000

  7. Role of normal Bacteria in Disease Prevention (colonization resistance) 1. Produce anti-microbial factors 2. Compete for binding sites on epithelial surface 3. Utilize nutrients more efficiently 4. Interact with intestinal lymphocytes to modulate immune response

  8. Genes and diet are the 2 major determinations of type and function of our gut bacteria but gut bacteria are altered by use of antibiotics, sometimes for months!

  9. Probiotics • Live microorganisms which, when consumed in adequate amounts, confer a health benefit “Good Bacteria”

  10. Probiotics Basic Requirements to be Effective • Must be live bacteria • Must survive acid and bile digestion

  11. Most Probiotics in 2009 are of only 2 major types- Lactobacillus and Bifido bacteria-YogurtSeveral others may be as good or better

  12. The Organism Gram +bacillus Anaerobic Spore forming Intestinal flora (up to 35% hospitalized patients, 3% of healthy adults) Leading cause of Antibiotic associated Diarrhea and colitis C Diff

  13. CDiff Pathogenicity Toxins are key- A and/or B. Non pathogenic strains don’t produce toxins.

  14. Mode of Transmission • Fecal-oral route • Poor hand hygiene practices • Poor infection control practices (use of contaminated equipment between patients) • Spore dormancy

  15. Diagnosis of CDI • Stool for C Diff toxin A&B EIA: Rapid, cheap, not very sensitive PCR: Rapid, moderate price, very sensitive

  16. Pseudomembranous Colitis Raised white/yellow nodules with skip areas of inflamed mucosa Endoscopy

  17. Key factors in contracting C Diff • Age over 65 • Antibiotic use, esp. Fluoroquinolones • Being in the hospital • Chemotherapy • Colorectal Surgery • Proton Pump Inhibitors • Renal failure • HAND HYGIENE

  18. C Diff • More Common Four Fold increase since 2001 in US 500,000 US cases; 15,000 deaths

  19. Law of Unintended Consequences • CMMS mandate for early use of antibiotics in suspected pneumonia • Strong correlation in antibiotic use 2002-2008 and C Diff rates

  20. C Diff • More Virulent New strain NAP1/027- makes 10-30 times more toxin

  21. War on C Diff committee • Dr. Ramgopal • Dr. Brown • Dr. Mellow • Dr. Rankin • Dr. Stokesberry • Dr. Muchmore • Gwen Harrington, RN

  22. War on C Diff • Prevention • Early Detection • Better Treatment

  23. C Diff Prevention • Isolation • Gowns • Gloves • Handwashing-Chlorhexidine in all rooms • BP cuffs, and stethoscopes in each room • Room equipment sterilization Dr. recommendations: Trashcan near door, for gown, etc disposal Sink area uncluttered, large gloves. Nurse recommendations: Doctors need to follow precautions also!

  24. Distribution of Clostridium Difficile isolates taken the room environments of three patients in an oncology unit Patient with C. diff Asymptomatic stool Patient with diarrhea colitis and diarrhea carrier of C diff culture neg for C diff Total sites 19/97 (19.6) 5/74 (6.8) 2/78 (2.6) cultured (+) No. positive/no. sampled (%)

  25. Early recognition=Earlier isolation, earlier onset of treatment

  26. Early Recognition Allow nurses to collect stool specimen for new onset diarrhea Stools are batched to lab in mid morning, so collect evening or early a.m. specimen Write Dr._______, phone order-Doctor will sign in a.m.

  27. War on C Diff Results • 4/08-3/09 C Diff 11.3 for 1000 admissions (national average 13 per 1000) • 4/09-3/10 C Diff 6.9 per 1000 admissions 40% decrease

  28. Study: Prevention of C Diff with Probiotics BMJ: Yogurt preparation (activia) Randomized control trial 9 of 53 C Diff with placebo 0 of 57 C Diff with yogurt No USA trials Lots of exclusions

  29. Efficacy of Probiotics in C Diff Prevention(am J. Gastro 2/10) • Hospitalized patients ages 50-70, newly started on antibiotics • Randomized to placebo, 50 billion cfu or 100 billion cfu capsules (50 billion cfu/capsule) Biok AAD: 44% with placebo 28% with 50 billion; 15% with 100 billion CDI: 23% with placebo 9% with 50 billion; 1% with 100 billion

  30. Co-Prescribe Probiotics with Antibiotics Write: Give Probiotics

  31. Treatment of Initial Episode of CDI • Average risk and average severity of CDI: Metronidazole • Patients condition not improving: Vancomycin • High risk patient or severe CDI (WBC, Creatinine, Albumin): Vancomycin • Ileus: Intra colonic Vancomycin, IV metronidazole, surgical consultation

  32. Intra colonic and/or fecal Vancomycin levels are arithmetically related to oral dose

  33. Oral Vanco Dose Relates to Colonic Vanco Levels 125mg Q6=350mg/L stool 250mg Q6=447mg/L 500mg Q6=714mg/L

  34. The Problem of Recurrent CDI • 25 % of patients with CDI will experience a recurrence • 50% of patients with recurrence will have multiple recurrences • Standard therapy often ineffective. Need innovative treatments

  35. Clinical Predictors of Recurrence of CDI • Age >65 • Severity of index infection • Antibiotic use after CDI treatment • Use of Acid Suppressants • Inadequate patient’s immune response

  36. Nitazoxanide(Alinia) • Approved for treatment of Giardia and Cryptospordia • As effective as Metronidazole and Vanco for initial cure • 50% cure rate in patients who failed Metronidazole

  37. Fidaxomicin • Oral agent vs. C Diff • Inhibits an enzyme (RNA polymerase) that results in death of organism • As good as Vancomycin in treatment • Significantly lower recurrence rate • Narrower spectrum of action-kills fewer “non C Diff” anaerobes • Cost

  38. Fidaxomicin vs. Vancomycin for CDI NEJM 2/2011 RCT: over 600 patients Cure rate of V=F ~90% (slightly less in severe disease) Recurrence rate F better than V: 25%vs. 15% But equal recurrence rate in patients with aggressive strain and patients with prior CDI.

  39. Humanized antibiodies to CDT A and B • Prevent recurrence Placebo controlled Company sponsored Worked best in less sick patients

  40. Did he say Fecal Transplant??YES

  41. What is Fecal Transplant? • Obtaining fecal matter from a healthy person and placing it in the intestine of another person

  42. Why would Fecal transfer work? • Antibiotics knock out many “good” bacteria that prevent C Diff proliferation • Normal person’s stool has these “good” bacteria

  43. Role of normal Bacteria in Disease Prevention (colonization resistance) 1. Produce anti-microbial factors 2. Compete for binding sites on epithelial surface 3. Utilize nutrients more efficently

  44. DECREASED MICROBIAL Diversity in RCDI • Small study • Genomic analysis of types of bacteria in stool: Controls 1st attack of CDI Recurrent CDI Many fewer species in RCDI and in 1 patient with 1st attack- developed recurrence 10 days later! Bacteria with colonizing resistance factors missing in RCDI

  45. Fecal Transplant Donor Exclusions • Antibiotics • Recent or chronic diarrhea • Immune suppression • Chemotherapy • Prior CDI

  46. Fecal Transfer Testing Donor blood: Hepatitis A,B,C;HIV;Syphlis Stool: CDiff, C&S, O&P $375.10 Recipient blood: Hepatitis A,B,C;HIV;Syphlis $275.00 (negotiated “Private Pay-discounted” by DLO)

  47. FT Process • D/C CDI treatment 48 hours pre procedure • Colon prep for patient • Mild laxative for donor • Stool mixed with non bacteriostatic saline • 400-600 cc placed in colon • Imodium 4mg

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