1. Dr Ajay Bhalla Add. Director & HOD Gastroenterology
& Hepatology Fortis Hospital Noida
2. World Health Organization: live microorganisms which when
administered in adequate amounts confer a health benefit on the
host They: Survive stomach acid and bile Establish residence in the
intestines Impart health benefits
5. Eli Metchnikoff - early 20th century (Russian Nobel
laureate, professor at Pasteur Institute in Paris) Observed
Bulgarians who drank milk fermented by lactic-acid producing
bacteria had long lives Lactic acid lowers gut pH and inhibits the
growth of some pathogenic bacteria. Metchnikoff began drinking
fermented milk and soon Parisian physicians did likewise. Henry
Tissier at Pasteur Institute identified bacteria common in
breastfed infant stool: Bifidobacter Lactobacillus acidophilus
breaks down lactose and allows lactose intolerant individuals to
drink milk
6. Colonization at birth with maternal species Specific
organisms vary by age in first year Become established by 1 year
Diet maternal milk, fermented milk, pickles, fermented soy
(tempeh), etc. Successful probiotic treatment leads to temporary
colonization
7. After reviewing a majority of the research and literature
relative to probiotic use in humans, it is clear that diarrhea is
the condition most beneficially treated by probiotic therapy. This
can include diarrhea associated with antibiotics, travel,
gastroenteritis, lactose intolerance, and Inflammatory Bowel
Disease. These areas were reviewed.
8. Diarrhea is frequent loose stools, along with an excessive
loss of fluid and electrolytes (K & Na especially), abdominal
cramping, pain, and often presence of a fever. It can be acute or
chronic, and is secondary to an underlying disease or condition or
pathogenic bacteria within the GI tract.
9. Protection of intestinal epithelial barrier function
Regulation of intestinal epithelial homeostasis Regulation of
intestinal microbial environment Modifications to commensal and
probiotic bacteria to enhance diarrhea prevention
10. integrity of the gastrointestinal epithelium L.
acidophilus; S. thermophilus, prevent enteroinvasive E. coli
disruption of intestinal epithelial barrier function VSL#3 enhances
T84 tight junctions Salmonella dublin L. acidophilus p38 mitogen
activated protein kinase and Akt signal transduction pathways
prevent cytokine-induced increases in intestinal epithelial
paracellular permeability
11. Inflammatory cytokines and chemokines intestinal epithelial
cell injury. L. casei downregulates Shigella flexneri by inhibition
of NFB-dependent transcription LGG prevents cytokine-induced
intestinal epithelial injury 1.by preventing apoptosis and
promoting cell growth 2.cytoprotective shock proteins
12. Disturbing the balance between the host and commensal
bacterial flora in GI tract is associated with
antibiotic-associated diarrhea fungal infections L. acidophilus and
Bifidobacterium spp. 1.prevent antibiotic treatment-induced
increases in facultative anaerobic bacteria 2.decrease
antibiotic-resistant enterococci.
13. toxin-receptor blockade strategy recombinant E. coli is
able to produce a lipopolysaccharide, which can bind heat- labile
enterotoxin, induces travelers diarrhea virulent V. cholerae
cholera toxin
14. Antibiotic-associated diarrhea (AAD) and Clostridium
difficile infection major pathological bacteria Lactobacillus GG
(LGG) Saccharomyces boulardii 1.significantly reduced the incidence
of antibiotic- associated diarrhea from 18.9% (placebo) to 5.7% (P
< 0.05) 2.combination with susceptible antibiotics decreases
recurrence of C. difficile infection
15. Administration of LGG, Saccharomyces boulardii, before and
during antibiotic treatment reduced the frequency and/or duration
of episodes and the severity of symptoms in many cases but was not
always effective Eradication Helicobacter pylori using
clarithromycin, amoxicillin, and omeprazol leads to diarrheas
Coadministration of S. boulardii during H. pylori eradication did
reduce AAD from 11.5 to 6.9%
16. AAD is defined as unexplained diarrhoea which develops
within few hours following antibiotic use upto 8 weeks after
antibiotic discontinuation
17. Its incidence has been noted to slowly increase over the
past few years, reaching up to 30% in some instances. Symptoms can
vary from mild self-limited disease to the more serious and severe
Clostridium difficile (C. difficile)-associated diarrhea (CDAD).
Luckily, CDAD is only responsible for an estimated 10%-20% of cases
of AAD Multiple risk factors for CDAD have been delineated, such as
advanced age, hospitalization, acid suppression, chemotherapy,
renal failure, gastrointestinal surgery and mechanical
ventilation
18. Common signs and symptoms For most people,
antibiotic-associated diarrhea causes mild signs and symptoms, such
as: Loose stools More-frequent bowel movements More-serious signs
and symptoms Some patients may have signs and symptoms of colitis
or pseudomembranous colitis, such as: Frequent, watery diarrhea
Abdominal pain and cramping Fever Mucus in your stool Bloody stools
Nausea Loss of appetite
19. Nearly all antibiotics can cause antibiotic- associated
diarrhea, colitis or pseudomembranous colitis. The antibiotics most
commonly linked to antibiotic-associated diarrhea include:
Cephalosporins, such as cefixime,Cefuroxime and cefpodoxime
Clindamycin Penicillins, such as amoxicillin and ampicillin
Macrolides(Erythromycin) Fluoroquinolones, such as ciprofloxacin
(Cipro) and levofloxacin
20. 20-30% of antibiotic-associated diarrhea Toxins detectable
in stool Onset during or within 10 weeks antibiotic use Associated
with all antibiotics 4 categories based on colon appearance Normal
colonic mucosa Mild erythema with some edema Granular, friable, or
hemorrhagic mucosa Pseudomembrane formation - mucosa shows raised
plaques with skip areas
21. Diverse clinical spectrum Diarrhea may be profuse/watery
Blood or mucus may be present Abdominal cramps Fever &
leukocytosis Large numbers of RBCs and WBCs in stool 95% have
positive stool toxin assays C. difficile toxin is very unstable
Toxin degrades at room temperature and may be undetectable within 2
hours after collection of a stool specimen False-negative results
occur when specimens are not promptly tested or kept refrigerated
until testing can be done
22. Pseudomembraneous colitis Toxic megacolon Perforation of
the colon Sepsis Death
23. ANTIBIOTIC EXPOSURE Gastrointestinal surgery or
manipulation Long length of stay in healthcare setting Infected
roommate Co-morbid illnesses Immunosuppression Advanced age
Proton-pump inhibitors and H2-blockers?
24. MORE FREQUENT LESS FREQUENT Cephalosporins (3rd and 4th
generation) Ticarcillin-clavulanate Ampicillin/Amoxicillin
Metronidazole Clindamycin Fluoroquinolones Other penicillins
Rifampin Macrolides 5-Fluorouracil Tetracyclines Methotrexate
Trimethoprim-Sulfamethoxazole Cyclophosphamide
26. Systematic review of 9 placebo-controlled studies (2 in
children) using various products: 60% reduction in incidence and
duration of antibiotic associated diarrhea compared with placebo
(P