Transcript 401_06_CDD_and_probi.. - University of Washington

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: Stomach
Stomach (0-103 cfu/ml):
Gram+ aerobes,
Lactobacillus &
Streptococcus
Predominant Flora: Vagina
Vagina: diverse aerobes & anaerobes including
Lactobacillus jensenii, Lactobacillus acidophilus,
Lactobacillus casei.
Predominant Flora: Urinary
Tract
Kidneys: sterile
Bladder: sterile
Urethra: 101-102 E. coli
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
Functions of Normal Flora
Digestion
 Production of vitamins
 Mucosal maturation
 Stimulate Immune System
 Attachment
 Intestinal transit
 Colonization 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
Saccharomyces boulardii and Antibiotic Associated
Diarrhea in Hospitalized Patients
N=180; site: University of Washington, Harborview
Hospital
Start
Stop
Stop
Antibiotic
Antibiotic
Study
Yeast continued for 14d
Start
Yeast
(within
48h)
Surawicz et al., Gastroenterol. 1989;96:981
Saccharomyces boulardii and Beta lactam Antibiotic
Associated Diarrhea in Hospitalized Patients
N=193; site: University of Washington, University of
Kentucky
Start
Stop
Stop
Antibiotic
Antibiotic
Study
yeast or placebo
continued for 3d
Start yeast
or placebo
McFarland et
al. Am J
Gastroenterol
1995;90:439448
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.
Lactobacillus GG & Prevention of
Infantile Nosocomial Diarrhea [Results]
33.3
35
30
*p<0.05
%
25
20
16.7
15
10
5
6.7*
2.2*
0
Placebo
(n=36)
Szajewska H. J Pediatr 2001;138:361-5.
L. GG (n=45)
ND
Rotaviral
D’Souza et al., BMJ 2002;324:1361
Lactobacilli and Pediatric Diarrhea Treatment
(L. rhamnosus and L. reuteri in hospital
setting)
50
45
40
35
30
25
20
15
10
5
0
treated
control
dur (h)
d5 dia (%)
d5 rota(%)
hosp days
N=69 Rosenfeldt et al., Pediatr Infec Dis 2002;21:411
Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)
McFarlan
d et al.,
JAMA;
271,
19131918,
(1994).
S. boulardii & High Dose
Vancomycin for C. difficile Disease
60
% CDD recurrences
50%
50
*p=0.05
40
30
16.7%
*
20
10
0
Placebo
(n=14)
Surawicz CM. Clin Infect Dis 2000;31:1012-7.
S. boulardii
(n=18)
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.
Comparison of Community-Acquired Matched Cases and Controls--Medication Variables
Dial, S. et al. JAMA 2005;294:2989-2995.
Copyright restrictions may apply.
Clostridium 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 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
Potential Advantages and
Disadvantages of Probiotics
Advantages
Disadvantages
Multiple Mechanisms of
Action
Few Controlled Trials
Resistance is Infrequent
Use May Reduce
Exposure to Antibiotics
Delivery of Microbial
Enzymes
Well Tolerated
Benefit to Risk Ration is
Favorable
Persistence Possible
Translocation Possible
Transfer of Resistance
Plasmids?
Infection Possible
Quality Control Issues
Regulatory Issues in USA
Lactobacillus rhamnosus GG
Dietary Supplement: Culturelle
Saccharomyces boulardii Dietary
Supplement: Florastor
Evidence supporting commercially available (USA)
probiotics*
condition L. acidophilus L. reueri
LGG
Sb
AAD
Uneven
Good
Good
Good
Acute
Adult
Acute
pediatric
Traveler
diarrhea
C. dif
?
?
Good
Good
?
?
Good
Good
?
?
Fair
Fair
?
?
Limited
Good
BV
Good** Good*** ?
?
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