Probiotics in GI Tract Disease

Probiotics in GI Tract DiseaseProbiotics in GI Tract Disease

Hala Fatima M.D.Hala Fatima M.D.Assistant Professor of Clinical Assistant Professor of Clinical

MedicineMedicineDepartment of MedicineDepartment of Medicine

Division of Division of Gastroenterology/HepatologyGastroenterology/Hepatology

Indiana University School of MedicineIndiana University School of Medicine

What are Probiotics?What are Probiotics?Live microorganisms which when Live microorganisms which when

administered in adequate amounts administered in adequate amounts confer a health benefit to the hostconfer a health benefit to the host

Not all have similar therapeutic Not all have similar therapeutic effectseffects

Interaction of Probiotics and Interaction of Probiotics and MicrofloraMicroflora

Antibiotic Associated DiarrheaAntibiotic Associated DiarrheaA recent meta-analysis (34 placebo controlled A recent meta-analysis (34 placebo controlled

trials) concluded that probiotics are associated trials) concluded that probiotics are associated with:with:52% decrease in antibiotic-associated diarrhea52% decrease in antibiotic-associated diarrhea8% reduction in traveler’s diarrhea8% reduction in traveler’s diarrhea57% reduction in risk of acute diarrhea in kids and 57% reduction in risk of acute diarrhea in kids and

26% in adults26% in adultsEffects did not vary significantly among the probiotic Effects did not vary significantly among the probiotic

strainsstrains

Sazawal SSazawal S et al.Efficacy of probiotics in prevention et al.Efficacy of probiotics in prevention of acute diarrhea: a meta-analysis of masked, of acute diarrhea: a meta-analysis of masked, randomized, placebo-controlled trials.randomized, placebo-controlled trials. Lancet Lancet Infect Dis. 2006 Jun;6(6):374-82.Infect Dis. 2006 Jun;6(6):374-82.

Antibiotic Associated DiarrheaAntibiotic Associated DiarrheaNot all studies used the same definition of Not all studies used the same definition of

AADAADPooled analysis included all diarrhea cases Pooled analysis included all diarrhea cases

whether or not they were due to C difficilewhether or not they were due to C difficileInsufficient data to suggest dose and duration Insufficient data to suggest dose and duration

of the probiotic preparationof the probiotic preparation

Antibiotic Associated DiarrheaAntibiotic Associated Diarrhea

McFarland LVMcFarland LV et al. et al. diarrhea and the treatment of diarrhea and the treatment of Clostridium Meta-analysis of probiotics for the Clostridium Meta-analysis of probiotics for the prevention of antibiotic associated difficile disease.prevention of antibiotic associated difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22Am J Gastroenterol. 2006 Apr;101(4):812-22 25 RCTs, total of 2810 patients with AAD25 RCTs, total of 2810 patients with AAD 13 studies(52%) reported a significant reduction of 13 studies(52%) reported a significant reduction of

AAD in probiotic treated group compared with placebo; AAD in probiotic treated group compared with placebo; 12 studies showed no difference12 studies showed no difference

ProbioticProbiotic # of RCT# of RCT pp value value

Saccharomyces Saccharomyces boulardiiboulardii

66 <0.0001<0.0001

Lactobacillus Lactobacillus rhamnosus GGrhamnosus GG

66 0.0060.006

Single strainsSingle strains 66 0.060.06

Mixtures of two Mixtures of two probioticsprobiotics

77 <0.0001<0.0001

Antibiotic Associated Diarrhea In Antibiotic Associated Diarrhea In ChildrenChildrenA meta-analysis of RCT showed that A meta-analysis of RCT showed that

probiotics reduce the risk of AAD in children; probiotics reduce the risk of AAD in children; for every 7 pts that would develop diarrhea for every 7 pts that would develop diarrhea while being treated with antibiotics, one while being treated with antibiotics, one fewer will develop AAD if also receiving fewer will develop AAD if also receiving probiotics.probiotics.

Szajewska H et al.Probiotics in the prevention of Szajewska H et al.Probiotics in the prevention of antibiotic-associated diarrhea in children: a antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials.meta-analysis of randomized controlled trials. J Pediatr. 2006 Sep;149(3):367-372.J Pediatr. 2006 Sep;149(3):367-372.

Clostridium Difficile DiarrheaClostridium Difficile Diarrhea McFarland LVMcFarland LV et al. et al. Meta-analysis of probiotics for the Meta-analysis of probiotics for the

prevention of antibiotic associated diarrhea and the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.treatment of Clostridium difficile disease. Am J Gastroenterol. Am J Gastroenterol. 2006 Apr;101(4):812-222006 Apr;101(4):812-22 Six RCTs for treatment of CDD, total of 354 patients; all adults: 3 Six RCTs for treatment of CDD, total of 354 patients; all adults: 3

trials exclusively for recurrent CDDtrials exclusively for recurrent CDD 2 trials (33%) showed a significant reduction in CDD recurrences in 2 trials (33%) showed a significant reduction in CDD recurrences in

the probiotic treated group as compared with placebo; 4 studies the probiotic treated group as compared with placebo; 4 studies showed no differenceshowed no difference

Only Only Saccharomyces boulardii Saccharomyces boulardii showed significant reduction in showed significant reduction in recurrences. recurrences. Lactobacillus rhamnosus GG and Lactobacillus Lactobacillus rhamnosus GG and Lactobacillus plantarumplantarum did not show significant differences did not show significant differences

A Pillai et al. A Pillai et al. Cochrane Database of Systematic ReviewsCochrane Database of Systematic Reviews 2008 2008 Four studies examined the use of probiotics in conjunction with Four studies examined the use of probiotics in conjunction with

conventional antibiotics (vancomycin or metronidazole) for the conventional antibiotics (vancomycin or metronidazole) for the treatment of recurrence or an initial episode of C. difficile colitis in treatment of recurrence or an initial episode of C. difficile colitis in adults.adults.

Insufficient evidence to recommend probiotic therapy as an adjunct Insufficient evidence to recommend probiotic therapy as an adjunct to antibiotic therapy for to antibiotic therapy for C. difficileC. difficile colitis. No evidence to support colitis. No evidence to support the use of probiotics alone in the treatment of the use of probiotics alone in the treatment of C. difficileC. difficile colitis. colitis.

Inflammatory Bowel DiseaseInflammatory Bowel DiseasePouchitis: level 1 evidencePouchitis: level 1 evidenceUC &CD: levels 2 & 3 evidenceUC &CD: levels 2 & 3 evidence

Probiotics in Inflammatory Bowel Probiotics in Inflammatory Bowel DiseaseDisease

Maintenance of Medical-Induced Maintenance of Medical-Induced Remission of Crohn’s DiseaseRemission of Crohn’s Disease

ReferenReferencece

StudyStudy nn DuratioDurationn

ProbioticProbiotic ControlControl Relapse Relapse rate rate (Probiotic(Probiotic))

Relapse Relapse rate rate (Placeb(Placebo)o)

pp valuvaluee

Malchow Malchow et al. et al. 19971997

RCTRCT 2828 12 12 monthsmonths

E.Coli NissleE.Coli Nissle PlaceboPlacebo Response: Response: 70%70%

ResponsResponse:30%e:30%

nsns

Guslandi Guslandi et al. et al. 20002000

Open-Open-labellabel

3232 6 6 monthsmonths

SaccharomySaccharomyces boulardii ces boulardii + + mesalamine mesalamine 2g/d2g/d

MesalaminMesalamine 3g/de 3g/d

Response: Response: 94%94%Relapse Relapse 6%6%

ResponsResponse:38%e:38%Relapse Relapse 38%38%

0.040.04

Schultz Schultz et al. et al. 20042004

RCT, RCT, DBDB


LGGLGG PlaceboPlacebo 60%60% 67%67% nsns

BousvaroBousvarous et al. us et al. 20052005

RCT, RCT, DBDB


LGGLGG PlaceboPlacebo(inulin)(inulin)

31%31% 17%17% 0.180.18

Treatment of Acute Active Crohn’s Treatment of Acute Active Crohn’s DiseaseDisease

ReferenReferencece

StudStudyy

nn DuratioDurationn

ProbioticProbiotic ControControll

RemissioRemission rate n rate (Probioti(Probiotic)c)

RemissioRemission rate n rate (Placebo)(Placebo)

pp valuvaluee

Malchow Malchow et et al.1997al.1997

RCTRCT 2828 12 12 weeksweeks

Steroid taper Steroid taper +E.Coli +E.Coli NissleNissle

PlacebPlaceboo

No differenceNo difference --

Gupta et Gupta et al.2000al.2000

OpenOpen-label-label

4 4 childrechildrenn

24 24 weeksweeks

LGGLGG n/an/a 100%100% n/an/a --

McCarthMcCarthy et y et al.2001al.2001


2525 12 12 weeksweeks

Lactobacillus Lactobacillus salivariussalivarius

n/an/a 76%76% n/an/a --

Fujimori Fujimori et al. et al. 20072007



Synbiotic Synbiotic mixture: mixture: BifidobacteriBifidobacterium Breve, um Breve, lactobacillus lactobacillus casei, casei, BifidobacteriBifidobacterium longum um longum and psylliumand psyllium

n/an/a Significant Significant improvemenimprovementt

n/an/a --

Maintenance of Surgical-Induced Maintenance of Surgical-Induced Remission of Crohn’s DiseaseRemission of Crohn’s Disease

ReferencReferencee

StudStudyy

nn DuratioDurationn

ProbioticProbiotic ControlControl Relapse Relapse rate rate (Probiotic)(Probiotic)

Relapse Relapse rate rate (Placebo)(Placebo)

pp valuevalue

Campieri Campieri et al.2000et al.2000

RCT, RCT, OLOL

4400

12 12 monthsmonths

3 mo of 3 mo of rifaximin rifaximin followed by followed by 9 mo of 9 mo of VSL#3 VSL#3 (6g)(6g)

12 mo of 12 mo of MesalamiMesalamine ne

20%20%Response: Response: endoscopic endoscopic 80%80%

40%40%Response: Response: endoscopic endoscopic 60%60%

0.050.05

Prantera Prantera et al. 2002et al. 2002

RCT, RCT, DBDB

4455

12 12 monthsmonths

LGGLGG PlaceboPlacebo 17%17%Response: Response: clinical clinical 83%; 83%; endoscopic endoscopic 40%40%

11%11%Response: Response: clinical clinical 89%; 89%; endoscopic endoscopic 65%65%

0.300.30

Marteau Marteau et al.2006et al.2006

RCT, RCT, DBDB

9988

6 6 monthsmonths

L. L. johnsoniijohnsonii

PlaceboPlacebo 49%49% 64%64% 0.150.15

Van Van Gossum et Gossum et al. 2007al. 2007

RCT, RCT, DBDB

7700

3 3 monthsmonths

L. L. johnsoniijohnsonii

PlaceboPlacebo 15%15% 14%14% 0.910.91

Maintenance of Remission in Ulcerative ColitisMaintenance of Remission in Ulcerative ColitisReferenReferencece


ProbioticProbiotic ControlControl Response Response to to Probiotic Probiotic (Remissio(Remission)n)

Response Response to to Placebo Placebo (Remissio(Remission)n)

pp valuvaluee

RembackeRembackennet al. 1999et al. 1999

RCT, RCT, DBDB


Escherichia Escherichia colicoliNissle 1917Nissle 1917

MesalamiMesalaminene1.2g/d1.2g/d

26%26% 25%25% nsns

Kruis et al. Kruis et al. 19971997

RCT, RCT, DBDB

120120 4 months4 months Escherichia Escherichia colicoliNissle 1917Nissle 1917


84%84% 89%89% 0.0120.012

Kruis et al. Kruis et al. 20042004

RCT, RCT, DBDB


Escherichia Escherichia colicoliNissle 1917Nissle 1917


55%55% 64%64% nsns

Venturi et Venturi et al. 1999al. 1999



VSL#3 (6g)VSL#3 (6g) NoneNone 75%75% n/an/a n/an/a

Ishikawa Ishikawa et al. 2003et al. 2003


Yakult Yakult fermented fermented milkmilk

PlaceboPlacebo 73%73% 10%10% 0.0180.018

Cui et al. Cui et al. 20042004

RCT, RCT, DBDB

3030 8 months8 months BifidobacteriaBifidobacteria PlaceboPlacebo Relapse: Relapse: 20%20%

Relapse: Relapse: 93%93%

<0.01<0.01

Zocco et Zocco et al. 2006al. 2006

R, R, Open-Open-labellabel


LGGLGGLGG + LGG + meselamine meselamine 2.4g/d2.4g/d

MesalamiMesalamine 2.4g/dne 2.4g/d

Relapse: Relapse: 15%15%

Relapse: Relapse: 20% 20%

0.770.77

Shanahan Shanahan et al. 2006 et al. 2006 (abs)(abs)

RCT, RCT, DBDB


L .salivariusL .salivariusB .infantisB .infantis

PlaceboPlacebo No significant benefitNo significant benefit --

Treatment of Acute Ulcerative ColitisTreatment of Acute Ulcerative ColitisReferenceReference StudyStudy nn DuratioDuratio

nnProbioticProbiotic ControlControl Response to Response to

Probiotic Probiotic (Remission)(Remission)

Response Response to Placebo to Placebo (Remission(Remission))

pp valuevalue

RembackeRembacken et al. n et al. 19991999


Prednisone taper + Prednisone taper + gentamicin + E.coli gentamicin + E.coli NissleNissle

Prednisone Prednisone taper + taper + gentamicin + gentamicin + mesalamine mesalamine 1.2g/d1.2g/d

68%68% 75%75% nsns

Matthes et Matthes et al. 2006al. 2006

RCT, RCT, DBDB

9090 1 month1 month E.coli Nissle enema (10, E.coli Nissle enema (10, 20, 40 ml)20, 40 ml)

PlaceboPlacebo Dose-Dose-dependent dependent response(27, response(27, 44, 53% 44, 53% resp)resp)

18%18% 0.040.04

Fedorak et Fedorak et al. 2003al. 2003



VSL#3VSL#3 n/an/a 63%63% n/an/a n/an/a

Biblioni et Biblioni et al. 2005al. 2005


3434 1.5 1.5 monthmonth

VSL#3VSL#3 n/an/a 53%53% n/an/a n/an/a

Tursi et al. Tursi et al. 20042004

R, R, Open-Open-labellabel


VSL#3 + balsalazide VSL#3 + balsalazide 2.25g/d2.25g/d

Balsalazide Balsalazide 4.5g/d4.5g/dMesalamine Mesalamine 2.4g/d 2.4g/d

80%80% 77%77%

53%53%

0.020.02

Guslandi et Guslandi et al. 2003al. 2003


2525 1 month1 month SaccharomycesSaccharomycesboulardiiboulardii

n/an/a 68%68% n/an/a n/an/a

Kato et al. Kato et al. 20042004

RCT, RCT, DBDB


Fermented milkFermented milk PlaceboPlacebo 40%40% 30%30% nsns

Borody et Borody et al. 2003al. 2003


66 1 week1 week Fecal enemas QDX5 Fecal enemas QDX5 days; retained for 6-8 days; retained for 6-8 hrshrs

n/an/a 100% 100% remission off remission off std meds by std meds by 4 mo; 4 mo; disease free disease free for 1-13 for 1-13 years FUPyears FUP

n/an/a n/an/a

PouchitisPouchitisMaintenance of antibiotic-induced remissionMaintenance of antibiotic-induced remissionTreatment of acute active pouchitisTreatment of acute active pouchitisPostoperative prevention of pouchitisPostoperative prevention of pouchitis

Clinical Trials in Pouchitis: Maintenance of Clinical Trials in Pouchitis: Maintenance of Anti-biotic Induced RemissionAnti-biotic Induced Remission

ReferenceReference StudyStudy nn DuratioDurationn

ProbiotiProbiotic & c & daily daily dosedose

ContrControlol

Response Response to to Probiotic Probiotic (Remissio(Remission)n)


pp valuvaluee

Gionchetti Gionchetti et al. 2000et al. 2000

RCT, DBRCT, DB 4040 9 9 monthsmonths

VSL#3 VSL#3 (6 g)(6 g)

PlacebPlaceboo

85%85% 0%0% <0.0<0.00101

Mimura et Mimura et al. 2004al. 2004

RCT, DBRCT, DB 3636 12 12 monthsmonths

VSL#3 VSL#3 (6 g)(6 g)

PlacebPlaceboo

85%85% 6%6% <0.0<0.00101

Shen et al. Shen et al. 20052005



VSL#3 VSL#3 (6 g)(6 g)

NoneNone n/an/a --

VSL#3: 4 strains of Lactobacillus (acidophilus, plantarum, casei, bulgaricus)3 strains of Bifidobacterium(breve, longum, infantis)1 strain of Streptococcus thermophilus

Clinical Trials in Pouchitis: Acute Active PouchitisClinical Trials in Pouchitis: Acute Active Pouchitis

ReferenReferencece

StudStudyy

nn DuratioDurationn

ProbioticProbiotic ControlControl Response to Response to Probiotic Probiotic (Remission)(Remission)


pp valuvaluee

Kuisma Kuisma et al. et al. 20032003

RCT, RCT, DBDB

2020 3 months3 months LactobacilluLactobacillus s rhamnosus rhamnosus GGGG

PlaceboPlacebo 0%0% 0%0% nsns

GosselinGosselink et al. k et al. 20042004

Open Open -label-label

111177

36 36 monthsmonths

LactobacilluLactobacillus s rhamnosus rhamnosus GGGG

Historical Historical controlscontrols

Relapse rate: 8%Relapse rate: 8% Relapse Relapse rate: 35%rate: 35%

0.010.01

Laake et Laake et al. 2003al. 2003


1010 1 month1 month CulturaCultura NoneNone 50% endoscopic 50% endoscopic improvement; no improvement; no histologic histologic improvementimprovement

n/an/a --

Laake et Laake et al. 2005al. 2005


5151 1 month1 month CulturaCultura NoneNone Significant Significant decrease in GI decrease in GI symptoms symptoms p<0.0005; decrease p<0.0005; decrease in eye symptoms in eye symptoms p=0.02p=0.02

59% remission59% remission

n/an/a --

Clinical Trials in Pouchitis: Post-Clinical Trials in Pouchitis: Post-Operative PreventionOperative Prevention

ReferenReferencece


ProbiotiProbioticc

ContrControlol

Response to Response to Probiotic Probiotic (Remission)(Remission)

Response Response to Placebo to Placebo (Remissio(Remission)n)

pp value value

GionchetGionchetti et al. ti et al. 20032003

RCT, RCT, DBDB

4400

12 12 monthsmonths

VSL#3 VSL#3 (3g)(3g)

PlacebPlaceboo

90%90%Relapse: 10%Relapse: 10%

60%60%Relapse: Relapse: 40%40%

<0.05<0.05

PouchitisPouchitisGionchetti P et al.High-dose probiotics for Gionchetti P et al.High-dose probiotics for

the treatment of active pouchitis.the treatment of active pouchitis. Dis Colon Dis Colon Rectum. 2007 Dec;50(12):2075-82Rectum. 2007 Dec;50(12):2075-8223 patients with mild pouchitis (PDAI score of 7-12) 23 patients with mild pouchitis (PDAI score of 7-12) Treated with VSL#3, 2 sachets b.i.d. (3,600 billion Treated with VSL#3, 2 sachets b.i.d. (3,600 billion

bacteria/day) X 4 weeksbacteria/day) X 4 weeks After remission treated with VSL#3, 1 sachet b.i.d. After remission treated with VSL#3, 1 sachet b.i.d.

(1,800 billion bacteria), as maintenance treatment (1,800 billion bacteria), as maintenance treatment X 6 months X 6 months

16/23 patients (69%) were in remission after 16/23 patients (69%) were in remission after treatment. treatment.

Conclusion: High doses of the probiotic VSL#3 are Conclusion: High doses of the probiotic VSL#3 are effective in the treatment of mild pouchitiseffective in the treatment of mild pouchitis

Irritable Bowel SyndromeIrritable Bowel SyndromeSeveral controlled trials, all short-term, modest Several controlled trials, all short-term, modest

magnitude of benefitmagnitude of benefitBifidobacterium infantis significantly more effective Bifidobacterium infantis significantly more effective

than placebo. However, benefit confined to only one of than placebo. However, benefit confined to only one of three doses tested; no clear dose-response three doses tested; no clear dose-response relationship (Whorwell et al. Am J Gastroenterol 2006)relationship (Whorwell et al. Am J Gastroenterol 2006)

Lactobacillus plantarum reduced flatulence, better Lactobacillus plantarum reduced flatulence, better overall GI function maintained at 12 months. No effect overall GI function maintained at 12 months. No effect on abdominal pain (Nobaek et al. Gastroenterol 2000)on abdominal pain (Nobaek et al. Gastroenterol 2000)

Combination of Lactobacillus plantarum and Combination of Lactobacillus plantarum and Bifidobacterium breve . Pain and severity scores Bifidobacterium breve . Pain and severity scores decreased significantly in the probiotic group after 14 decreased significantly in the probiotic group after 14 days of treatment (Saggioro et al. J Clin Gastroenterol days of treatment (Saggioro et al. J Clin Gastroenterol 2004)2004)

Irritable Bowel SyndromeIrritable Bowel SyndromeVSL#3 reduced bloating ; no effect on pain, gas VSL#3 reduced bloating ; no effect on pain, gas

or urgency (Kim et al. Aliment Pharmacol Ther or urgency (Kim et al. Aliment Pharmacol Ther 2003)2003)

Lactbacillus GG – no benefit (O’Sullivan et al. Lactbacillus GG – no benefit (O’Sullivan et al. Dig Liver Dis 2000)Dig Liver Dis 2000)

Multispecies probiotic :Lactobacillus rhamnosus Multispecies probiotic :Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and freudenreichii ssp. shermanii JS and Bifidobacterium animalis. The composite Bifidobacterium animalis. The composite irritable bowel syndrome score had at 5 months irritable bowel syndrome score had at 5 months decreased 14 points from baseline vs. 3 points decreased 14 points from baseline vs. 3 points with placebo (P = 0.0083). Especially, with placebo (P = 0.0083). Especially, distension and abdominal pain were affected.distension and abdominal pain were affected.(Kajander et al. Aliment Pharmacol Ther 2007)(Kajander et al. Aliment Pharmacol Ther 2007)

Other GI DisordersOther GI DisordersLactose Intolerance: Lactose Intolerance:

Meta-analysis show inconsistent results (Levri et al. Meta-analysis show inconsistent results (Levri et al. J Fam Pract 2005)J Fam Pract 2005)

Benefit remains unproven.Benefit remains unproven.Collagenous Colitis: Collagenous Colitis:

Possible benefit of E.coli Nissle 1917 (Tromm et al. Possible benefit of E.coli Nissle 1917 (Tromm et al. Z Gastroenterol 2004)Z Gastroenterol 2004)

Placebo-controlled trial: Combination of Placebo-controlled trial: Combination of Lactobacillus acidophilus and Bifidobacterium Lactobacillus acidophilus and Bifidobacterium animalis caused improvement in symptoms but had animalis caused improvement in symptoms but had no significant effect on primary endpoints (Wildt et no significant effect on primary endpoints (Wildt et al.Inflamm Bowel Dis 2006)al.Inflamm Bowel Dis 2006)

Meta- analysis Cochrane Database Syst Rev. 2008 : Meta- analysis Cochrane Database Syst Rev. 2008 : No evidence for the effectiveness probiotics. No evidence for the effectiveness probiotics.

Diverticular Colitis: Diverticular Colitis: Combination of VSL#3 and an oral beclomethasone Combination of VSL#3 and an oral beclomethasone

was beneficial in a case serieswas beneficial in a case series

Safety (2)Safety (2)

Infection: extremely rare- represent 0.05% -0.4% of Infection: extremely rare- represent 0.05% -0.4% of infective endocarditis or bacteremiainfective endocarditis or bacteremia

Reported case of liver abscess caused by lactobacillus Reported case of liver abscess caused by lactobacillus rhamnosus (500 ml/d). Recovered with surgical drainage rhamnosus (500 ml/d). Recovered with surgical drainage and antibiotics.and antibiotics.

Bacteremia reported in premature babies with short-gut Bacteremia reported in premature babies with short-gut syndromesyndrome

Cannon et al. Eur J Clin Microbiol Infect Dis 2005.Cannon et al. Eur J Clin Microbiol Infect Dis 2005. Review of 200 cases of lactobacillus infection 1950-2003; Review of 200 cases of lactobacillus infection 1950-2003;

114 cases of bacteremia114 cases of bacteremia Mortality rate 32%Mortality rate 32% All patients had significant morbidity including malignancyAll patients had significant morbidity including malignancy 62 cases of IE with 22.9% mortality rate.62 cases of IE with 22.9% mortality rate.

Safety (2)Safety (2) Reports of Saccharomyces cervisiae fungemia; some with Reports of Saccharomyces cervisiae fungemia; some with

CVC as the playing a roleCVC as the playing a role Prospective study from Finland reported that the marked Prospective study from Finland reported that the marked

increase in consumption of probiotics has not led to an increase in consumption of probiotics has not led to an increased rate of opportunistic infectionincreased rate of opportunistic infection

Most of the cases are in immunocompromised patients or Most of the cases are in immunocompromised patients or those with serious underlying disease states, malignancy, those with serious underlying disease states, malignancy, prior surgery or on hyperalimentation.prior surgery or on hyperalimentation.

Antibiotic resistance - theoretic riskAntibiotic resistance - theoretic risk Overall safe and well-tolerated.Overall safe and well-tolerated.

Summary (1)Summary (1)Probiotics are effective in reducing the incidence Probiotics are effective in reducing the incidence

of antibiotic induced diarrhea; no definite of antibiotic induced diarrhea; no definite information available regarding dose or timing – information available regarding dose or timing – not recommended routinelynot recommended routinely

Unclear if probiotics can shorten the period of Unclear if probiotics can shorten the period of diarrhea in those who have already developed itdiarrhea in those who have already developed it

Studies for C diff treatment or prevention are Studies for C diff treatment or prevention are inconclusive - routine use cannot be inconclusive - routine use cannot be recommended due to reports of Saccharomyces recommended due to reports of Saccharomyces fungemiafungemia

Reasonable to recommend probiotics to adults Reasonable to recommend probiotics to adults and children with presumed infectious diarrheal and children with presumed infectious diarrheal illness with the hope of reducing the duration of illness with the hope of reducing the duration of symptoms by 17 to 30 hourssymptoms by 17 to 30 hours

Summary (2)Summary (2)Evidence for use strongest in pouchitis esp. Evidence for use strongest in pouchitis esp.

with VSL#3. Reasonable option along with with VSL#3. Reasonable option along with medical therapy. Long-term efficacy uncertain.medical therapy. Long-term efficacy uncertain.

E.coli Nissle equivalent to 5 ASA in UC and E.coli Nissle equivalent to 5 ASA in UC and may be used as enemas for distal disease. may be used as enemas for distal disease. Could be considered in patients intolerant or Could be considered in patients intolerant or resistant to 5-ASA preparationsresistant to 5-ASA preparations

Studies of probiotics in CD have been Studies of probiotics in CD have been disappointing and a recent systematic review disappointing and a recent systematic review has concluded that their use could not be has concluded that their use could not be recommended on the available evidence recommended on the available evidence (Rolfe et al. 2006)(Rolfe et al. 2006)

Summary (3)Summary (3)Irritable bowel syndrome — benefit of Irritable bowel syndrome — benefit of

probiotics remains unproven. Bifidobactrium probiotics remains unproven. Bifidobactrium infantisinfantis

H.pylori — Probiotics not recommended in H.pylori — Probiotics not recommended in the treatment or as an adjunct for eradicationthe treatment or as an adjunct for eradication

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Probiotics in GI Tract Disease