401 06 cdd_and_probiotics(1)
TRANSCRIPT
Probiotics Terms:
•Probiotic – Probiotics are live microorganisms (bacteria or yeasts) which, when administered in adequate amounts, confer a health benefit on the host
•Prebiotic - nutritional supplement taken to increase the amounts of beneficial bacterial in the gut or vagina. Example “FOS” (fructose oligosaccharides)
•Biotherapeutic agent - microorganism used for specific therapeutic activity in humans
•Nutriceutical - food products with beneficial effects in preventing or treating diseases
Predominant Flora: StomachPredominant Flora: Stomach
Stomach (0-103 cfu/ml): Gram+ aerobes, Lactobacillus & Streptococcus
Predominant Flora: VaginaPredominant Flora: Vagina
Vagina: diverse aerobes & anaerobes including Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus casei.
Predominant Flora: Urinary Predominant Flora: Urinary TractTract
Kidneys: sterile
Bladder: sterile
Urethra: 101-102 E. coli
Predominant Flora: IntestinesPredominant 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
Functions of Normal FloraFunctions of Normal Flora
DigestionDigestion Production of vitaminsProduction of vitamins Mucosal maturationMucosal maturation Stimulate Immune SystemStimulate Immune System AttachmentAttachment Intestinal transitIntestinal transit Colonization resistanceColonization resistance
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
Stop Antibiotic
Start Antibiotic
Start Yeast (within 48h)
Stop Study
Yeast continued for 14d
Saccharomyces boulardii and Antibiotic Associated Diarrhea in Hospitalized PatientsN=180; site: University of Washington, Harborview Hospital
Surawicz et al., Gastroenterol. 1989;96:981
Stop Antibiotic
Start Antibiotic
Start yeast or placebo
Stop Study
yeast or placebo continued for 3d
Saccharomyces boulardii and Beta lactam Antibiotic Associated Diarrhea in Hospitalized PatientsN=193; site: University of Washington, University of Kentucky
McFarland et al. Am J Gastroenterol 1995;90:439-448
LactobacillusLactobacillus GG & Prevention of GG & Prevention of Infantile Nosocomial Diarrhea Infantile Nosocomial Diarrhea
[Methods][Methods] DBPC in PolandDBPC in Poland 81 hospitalized children (1-36 months old)81 hospitalized children (1-36 months old) No diarrhea on admissionNo diarrhea on admission Randomized during stay:Randomized during stay:
–– LGG (12 x 10 LGG (12 x 109 9 CFU/d)CFU/d) –– Placebo Placebo
Szajewska H. J Pediatr 2001;138:361-5.
Lactobacillus Lactobacillus GG & Prevention of GG & Prevention of Infantile Nosocomial Diarrhea Infantile Nosocomial Diarrhea [Results][Results]
0
5
10
15
20
25
30
35
%
NDRotaviral
6.7*2.2*
33.3
16.7
*p<0.05
L. GG (n=45) Placebo (n=36)
Szajewska H. J Pediatr 2001;138:361-5.
D’Souza et al., BMJ 2002;324:1361
Lactobacilli and Pediatric Diarrhea Treatment Lactobacilli and Pediatric Diarrhea Treatment (L. rhamnosus and L. reuteri in hospital (L. rhamnosus and L. reuteri in hospital
setting)setting)
05
1015
202530
3540
4550
dur (h) d5 dia (%) d5 rota(%) hosp days
treatedcontrol
N=69 Rosenfeldt et al., Pediatr Infec Dis 2002;21:411
Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)
McFarland et al., JAMA; 271, 1913-1918, (1994).
S. boulardiiS. boulardii & High Dose & High Dose Vancomycin for Vancomycin for C. difficileC. difficile Disease Disease
0
10
20
30
40
50
60
% C
DD
rec
urre
nces
50%
16.7%*
Surawicz CM. Clin Infect Dis 2000;31:1012-7.
S. boulardii (n=18)
Placebo(n=14)
*p=0.05
Copyright restrictions may apply.
Dial, S. et al. JAMA 2005;294:2989-2995.
Rates of Clostridium difficile per 100 000 Patients in the United Kingdom General Practice Research Database
Copyright restrictions may apply.
Dial, S. et al. JAMA 2005;294:2989-2995.
Comparison of Community-Acquired Matched Cases and Controls--Medication Variables
Clostridium difficile DiseaseClostridium difficile Disease• C. difficle makes 2 toxins. Recent strains are more toxinogenic
•severity ranges from simple antibiotic associated diarrhea to mild colitis to pseudomembranous colitis to toxic megacolon to death
•Relapses following treatment are common
•Risk factors are antimicrobial exposure; recently gastric acid suppressive therapy has also been found to be a significant risk
•All antibiotics have some (undefined) risk but those impacting the anaerobic intestinal microflora may have a higher risk (beta lactams, clindamycin, tetracyclines, etc)
•Treatment is metronidazole 250mg QID as a first try. If treatment failure or relapse, use vancomycin PO 125mg QID. If failure, 500mg QID.
•Use Saccharomyces boulardii probiotic to prevent relapses. Dose is 500mg BID for 4-6weeks.
Other Uses for Probiotics –Limited DataOther 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
Multiple Mechanisms of Action
Resistance is Infrequent
Use May Reduce Exposure to Antibiotics
Delivery of Microbial Enzymes
Well Tolerated
Benefit to Risk Ration is Favorable
Few Controlled Trials
Persistence Possible
Translocation Possible
Transfer of Resistance Plasmids?
Infection Possible
Quality Control Issues
Regulatory Issues in USA
Advantages Disadvantages
Potential Advantages and Disadvantages of Probiotics
Lactobacillus rhamnosus GG Dietary Supplement: Culturelle
Saccharomyces boulardii Dietary Supplement: Florastor
Evidence supporting commercially available (USA) Evidence supporting commercially available (USA) probiotics*probiotics*
AADAAD UnevenUneven GoodGood GoodGood GoodGood
Acute Acute AdultAdult
?? ?? GoodGood GoodGood
Acute Acute pediatricpediatric
?? ?? GoodGood GoodGood
Traveler Traveler diarrheadiarrhea
?? ?? FairFair FairFair
C. difC. dif ?? ?? LimitedLimited GoodGood
BVBV Good**Good** Good***Good*** ?? ??
condition L. acidophilus L. reueri LGG Sb
L. acidophilus=Lactinex; L. reueri=Probiotica; LGG=Culturelle; Sb=Florastor; ** strains tested not yet available in USA
Probiotics Summary
•Living microorganisms with multiple mechanisms of action
•Good safety profile
•Some applications to prevent and treat infectious diseases
•An alternative to antibiotics in some situations
•May have other applications, e.g. allergy, cancer, colitis, IBS
•Product selection is very important