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Probiotics Terms:

Probiotic Probioticsarelivemicroorganisms(bacteria
oryeasts)which,whenadministeredinadequateamounts,
conferahealthbenefitonthehost
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
travelers 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

16.7

20
15
10
5

6.7*
2.2*

Placebo
(n=36)
Szajewska H. J Pediatr 2001;138:361-5.
L. GG (n=45)

ND
Rotaviral

DSouza 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,etal.,DigestiveDiseasesandSciences,Vol.47,No.11(Nov2002)

McFarlan
detal.,
JAMA;
271,
1913
1918,
(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


Crohns 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

Good

Good

Acute
?
pediatric

Good

Good

Traveler ?
diarrhea

Fair

Fair

C. dif

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