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401 06 cdd_and_probiotics(rgfrgr1)


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  • 1. Probiotics Terms:•Probiotic – Probiotics are live microorganisms (bacteriaor yeasts) which, when administered in adequate amounts,confer a health benefit on the host•Prebiotic - nutritional supplement taken to increase theamounts of beneficial bacterial in the gut or vagina.Example “FOS” (fructose oligosaccharides)•Biotherapeutic agent - microorganism used for specifictherapeutic activity in humans•Nutriceutical - food products with beneficial effects inpreventing or treating diseases
  • 2. Predominant Flora: Stomach Stomach (0-103 cfu/ml): Gram+ aerobes, Lactobacillus & Streptococcus
  • 3. Predominant Flora: Vagina Vagina: diverse aerobes & anaerobes including Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus casei.
  • 4. Predominant Flora: Urinary Tract Kidneys: sterile Bladder: sterile Urethra: 101-102 E. coli
  • 5. Predominant Flora: Intestines Small intestine: Proximal ileum (103-104 cfu/ml) aerobic Gram+ Distal ileum (1011-1012 cfu/ml) Gram- anaerobes Colon (1011-1012 cfu/ml): Bacteroides, Eubacteria, Peptostreptococci, E. coli, Bifidobacterium, Fusobacteria
  • 6. Functions of Normal Flora  Digestion  Production of vitamins  Mucosal maturation  Stimulate Immune System  Attachment  Intestinal transit  Colonization resistance
  • 7. Use of Probiotics in Larger Controlled Trials in Humans•Prevention of Diarrhea •antibiotic associated diarrhea •infantile diarrhea •traveler’s diarrhea•Treatment of Diarrhea • Clostridium difficile disease •acute diarrhea - pediatric and adult
  • 8. Saccharomyces boulardii and Antibiotic Associated Diarrhea in Hospitalized Patients N=180; site: University of Washington, Harborview HospitalStart Stop StopAntibiotic Antibiotic Study Yeast continued for 14d Start Yeast (within 48h)
  • 9. Surawicz et al., Gastroenterol. 1989;96:981
  • 10. Saccharomyces boulardii and Beta lactam Antibiotic Associated Diarrhea in Hospitalized Patients N=193; site: University of Washington, University of KentuckyStart Stop StopAntibiotic Antibiotic Study yeast or placebo continued for 3d Start yeast or placebo
  • 11. McFarland etal. Am JGastroenterol1995;90:439-448
  • 12. Lactobacillus GG & Prevention of Infantile Nosocomial Diarrhea [Methods] DBPC in Poland 81 hospitalized children (1-36 months old) No diarrhea on admission Randomized during stay: – LGG (12 x 109 CFU/d) – Placebo Szajewska H. J Pediatr 2001;138:361-5.
  • 13. Lactobacillus GG & Prevention ofInfantile Nosocomial Diarrhea [Results] 33.3 35 30 *p<0.05 25 20 16.7 ND% 15 Rotaviral 10 6.7* 5 2.2* 0 L. GG (n=45) Placebo (n=36) Szajewska H. J Pediatr 2001;138:361-5.
  • 14. D’Souza et al., BMJ 2002;324:1361
  • 15. Lactobacilli and Pediatric Diarrhea Treatment (L. rhamnosus and L. reuteri in hospital setting) 50 45 40 35 30 25 treated 20 control 15 10 5 0 dur (h) d5 dia (%) d5 rota(%) hosp days N=69 Rosenfeldt et al., Pediatr Infec Dis 2002;21:411
  • 16. Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)
  • 17. McFarland et al.,JAMA;271,1913-1918, (1994).
  • 18. S. boulardii & High DoseVancomycin for C. difficile Disease 60 50% 50 *p=0.05 % CDD recurrences 40 30 20 16.7% * 10 0 Placebo S. boulardii (n=14) (n=18) Surawicz CM. Clin Infect Dis 2000;31:1012-7.
  • 19. Rates of Clostridium difficile per 100 000 Patients in the United Kingdom General Practice Research Database Dial, S. et al. JAMA 2005;294:2989-2995.Copyright restrictions may apply.
  • 20. Comparison of Community-Acquired Matched Cases and Controls--Medication Variables Dial, S. et al. JAMA 2005;294:2989-2995.Copyright restrictions may apply.
  • 21. Clostridium difficile Disease• C. difficle makes 2 toxins. Recent strains are more toxinogenic•severity ranges from simple antibiotic associated diarrhea to mildcolitis to pseudomembranous colitis to toxic megacolon to death•Relapses following treatment are common•Risk factors are antimicrobial exposure; recently gastric acidsuppressive therapy has also been found to be a significant risk•All antibiotics have some (undefined) risk but those impacting theanaerobic intestinal microflora may have a higher risk (betalactams, clindamycin, tetracyclines, etc)•Treatment is metronidazole 250mg QID as a first try. If treatmentfailure or relapse, use vancomycin PO 125mg QID. If failure,500mg QID.•Use Saccharomyces boulardii probiotic to prevent relapses. Doseis 500mg BID for 4-6weeks.
  • 22. Other Uses for Probiotics –Limited Data•Crohn’s Disease•Ulcerative Colitis•Pouchitis•Allergy/Exema•Irritable Bowel Syndrome Dental caries•High Cholesterol Urinary Tract Infections•Helicobacter pylori• Lactose Intolerance•Candida vaginal infections•Bacterial Vaginosis
  • 23. Potential Advantages and Disadvantages of ProbioticsAdvantages DisadvantagesMultiple Mechanisms of Few Controlled TrialsAction Persistence PossibleResistance is Infrequent Translocation PossibleUse May Reduce Transfer of ResistanceExposure to Antibiotics Plasmids?Delivery of Microbial Infection PossibleEnzymes Quality Control IssuesWell Tolerated Regulatory Issues in USABenefit to Risk Ration isFavorable
  • 24. Lactobacillus rhamnosus GGDietary Supplement: Culturelle
  • 25. Saccharomyces boulardii Dietary Supplement: Florastor
  • 26. Evidence supporting commercially available (USA) probiotics*condition L. acidophilus L. reueri LGG SbAAD Uneven Good Good GoodAcute ? ? Good GoodAdultAcute ? ? Good GoodpediatricTraveler ? ? Fair FairdiarrheaC. dif ? ? Limited GoodBV Good** Good*** ? ?L. acidophilus=Lactinex; L. reueri=Probiotica; LGG=Culturelle; Sb=Florastor; **strains tested not yet available in USA
  • 27. Probiotics Summary•Living microorganisms with multiple mechanismsof action•Good safety profile•Some applications to prevent and treat infectiousdiseases•An alternative to antibiotics in some situations•May have other applications, e.g. allergy, cancer,colitis, IBS•Product selection is very important