Enterogermina Wilhelm 2011

960 n The Annals of Pharmacotherapy n 2011 July/August, Volume 45 theannals.com

H elicobacter pylori is a spiral-shaped,gram-negative bacterium that re-sides between the mucous layer and sur-face epithelial cells in the stomach or in-testines.1 It colonizes the gastrointestinallining when the mucosal integrity has beencompromised by environmental factorssuch as increased acid production, phar-maceutical agents (nonsteroidal antiin-flammatory drugs, aspirin, selective sero-tonin reuptake inhibitors), dietary toxins,or stress.2,3 H. pylori infects 30-40% of thepopulation in developed countries like theUS.3 H. pylori infection is more commonin lower socioeconomic conditions and isprevalent in about 80-90% of the popula-tion in developing countries.4 This colo-nization leads to ulcerations in the mucos-al lining and causes peptic ulcer disease inup to 20% of infected individuals.5 Symp-toms of peptic ulcer disease include ab-dominal pain, nausea, reflux symptoms,and vomiting; it is the most commoncause of upper gastrointestinal bleedingand perforation.2 Symptoms and compli-cations associated with peptic ulcer disease lead to job absen-teeism, reduced work productivity, and lower health-relatedquality of life. Direct costs related to outpatient and inpatientvisits and medication costs are a burden to the health-caresystem and to patients.2

One of the main treatment goals for peptic ulcer diseaseis H. pylori eradication.6 Treatment of H. pylori consists oftriple or quadruple therapy that includes antimicrobials andacid suppressive therapy with a proton pump inhibitor, his-

tamine receptor antagonist, and bismuth.3 Table 1 includesthe first-line recommendations for H. pylori eradicationrecommended by the American College of Gastroenterolo-gy.3 Treatment will fail in approximately 10-35% of pa-tients, and H. pylori will remain resulting from several fac-tors, including nonadherence related to adverse effects orcomplicated dosing regimens, high prescription costs, andantibiotic resistance.7,8

Probiotics are microorganisms that help maintain normalgut flora and prevent colonization by pathogenic organismsvia a number of mechanisms, including competitive inhibi-tion of gut wall adhesion of pathogenic microorganisms and

Treating Bugs with Bugs: The Role of Probiotics as Adjunctive

Therapy for Helicobacter pylori

Sheila M Wilhelm, Jennifer L Johnson, and Pramodini B Kale-Pradhan

Infectious Diseases

Author information provided at end of text.

OBJECTIVE: To review the literature on the role of probiotics as adjunctive therapyin the treatment of Helicobacter pylori infections.DATA SOURCES: Literature was accessed through MEDLINE (1966-March 2011)using the terms H. pylori, probiotic, Lactobacillus, Bifidobacterium, Saccharomyces,Bacillus clausii, and Propionibacterium. Article references were hand-searched foradditional relevant articles and abstracts.STUDY SELECTION AND DATA EXTRACTION: All English-language articles publishedin full were evaluated. Randomized, double-blind, placebo-controlled trialsassessing the use of probiotics combined with standard eradication therapy of H.pylori infection in adults were included in the review.DATA SYNTHESIS: Various probiotics, including Lactobacillus spp., Saccharomycesspp., Bifidobacterium spp., and B. clausii, reduce adverse effects such as nausea,taste disturbance, diarrhea, and epigastric pain, and increase tolerability of H.pylori eradication therapy. Based on the studies reviewed, probiotics do not affectH. pylori eradication rates. CONCLUSIONS: Probiotics may be beneficial in reducing adverse effects andincreasing tolerability of H. pylori eradication regimens. They may especially behelpful in patients with recurrent H. pylori infection and a history of gastrointestinaladverse effects with antibiotics. Pharmacists can play an important role ineducating patients regarding probiotic use during H. pylori eradication therapy. KEY WORDS: Bifidobacterium, H. pylori, Lactobacillus, probiotic, Saccharomyces.Ann Pharmacother 2011;45:960-6.Published Online, 21 Jun 2011, theannals.com, DOI 10.1345/aph.1Q104

Copyrighted material. Reproduo proibida.

generalized immune system enhancement because of theability of probiotics to bind to epithelial cells.9-11 When probi-otics bind to epithelial cells, they release substances that pre-vent the growth of pathogens and modulate intestinal perme-ability.

Data Sources and Selection

This review examines the role of probiotics in the treat-ment of H. pylori infection. A literature search usingMEDLINE (1966-March 2011) was completed to identifyrandomized, double-blind, placebo-controlled trials pub-lished in full in English assessing the use of probioticscombined with standard eradication therapy of H. pyloriinfection. The search included some of the most commonand familiar strains of probiotics used in gastrointestinaldisorders: Helicobacter pylori, probiotic, Lactobacillus, Bi-fidobacterium, Saccharomyces, Bacillus clausii, and Propi-onibacterium. The search was further limited to adults.Bibliographies of recent review articles and systematic re-views were hand-searched for relevant trials.

Clinical Studies

Four randomized, double-blind, placebo-controlled tri-als assessing the use of probiotics combined with standarderadication therapy of H. pylori infection were identified(Table 2).12-15 In all 4 trials, participants were healthy and,although they were asymptomatic, the results of H. pyloricultures were positive. All trials assessed antibiotic-associ-ated adverse effects and treatment tolerability as the prima-ry outcome. H. pylori eradication rate was the secondaryoutcome in each of the trials.

In the first trial, 60 participants were treated with tripleantibiotic therapy on days 1-7 and Lactobacillus GG on

days 1-14.12 Probiotics significantly improved symptoms,including nausea (10% vs 36.6%; RR 0.3; 95% CI 0.1 to0.9), taste disturbance (23.3% vs 50%; RR 0.5; 95% CI 0.2to 0.9), and diarrhea (3.3% vs 26.6%; RR 0.1; 95% CI 0.1to 0.9); however, epigastric pain (33.3% vs 30%; RR 1.1;95% CI 0.5 to 2.3) did not significantly improve duringeradication treatment. These effects were not seen duringthe week following the completion of antibiotic therapy.Eradication rates did not differ significantly between thegroups (83.3% vs 80%).

In the second trial, 97 individuals were randomized toreceive Lactobacillus GG, Saccharomyces boulardii, Lac-tobacillus acidophilus, Bifidobacterium lactis, or placeboon days 1-14, with H. pylori treatment on days 1-7.13 Probi-otics significantly improved symptoms, including taste dis-turbance (RR 0.15; 95% CI 0.05 to 0.46; p = 0.0027) anddiarrhea (RR 0.16; 95% CI 0.04 to 0.56; p = 0.018); how-ever, nausea (p = 0.75) and epigastric pain (p = 0.7) did notsignificantly improve during H. pylori treatment. These ef-fects were seen during the treatment week and were notmaintained following the completion of antibiotic therapy.All of the differences were noted between the probioticsand placebo. None of the probiotics was superior to anoth-er. Eradication rates were not significantly different amongthe 4 groups receiving probiotics.

In the third trial 47 patients were studied using a milk-based fruit drink containing Lactobacillus GG, Propioni-bacterium, Bifidobacterium, or placebo on days 1-28 andtriple antibiotic therapy days 1-7.14 Probiotics did not sig-nificantly improve symptoms, including nausea (13% vs21%; mean difference 8%; 95% CI 32 to 16), taste dis-turbance (70% vs 67%; mean difference 3%; 95% CI 24to 30), diarrhea (17% vs 8%; mean difference 9%; 95% CI12 to 32), and epigastric pain (17% vs 29%; mean differ-ence 12%; 95% CI 36 to 14). Eradication rates did not

The Annals of Pharmacotherapy n 2011 July/August, Volume 45 n 961theannals.com

Table 1. First-Line Regimens for Helicobacter pylori Eradication3

Duration Eradication Regimen Medications (days) Rates

Triple therapy (clarithromycin-based) Proton pump inhibitora 10-14 70-85%Clarithromycin 500 mg po bidAmoxicillin 1000 mg po bid or metronidazole 500 mg po bid

Quadruple therapy (bismuth-based) Proton pump inhibitor or ranitidine 150 mg po bid 10-14 75-90%Bismuth subsalicylate 525 mg po qidMetronidazole 250 mg po qidTetracycline 500 mg po qid

Alternative therapy not validated in the US First 5 days: 10 >90%proton pump inhibitoramoxicillin 1000 mg po bid

Last 5 days:proton pump inhibitorclarithromycin 500 mg bidtinidazole 500 mg bid

aStandard doses for proton pump inhibitors are as follows: esomeprazole 40 mg/day po, lansoprazole 30 mg po bid, omeprazole 20 mg po bid, pan-toprazole 40 mg po bid, rabeprazole 20 mg po bid.



SM Wilhelm et al.

Tabl

e2.

Rand

omize

d,Do

uble-

Blind

,Pla

cebo

-Con

trolle

dTr

ials

ofPr

obiot

icsPl

usEr

adica

tion

Ther

apyf

orHe

licob

acte

rpylo

riIn

fecti

ons1

2-15

Dia

gnos

ticPr

obio

ticA

ntib

iotic

Mea

sure

men

tR

esul

tsA

utho

rPa

tient

sM

etho

dsR

egim

enR

egim

enO

utco

mes

Too

ls(P

robio

ticvs

Cont

rol)

Arm

uzzi

N=

60UB

T,se

rolo

gyLa

ctob

acillu

sG

G6

10

9R

abep

razo

le20

mg

bid,

Prim

ary:

antib

iotic

-Qu

estio

nnair

e;Sy

mpt

oms:

(2001

)12M

/F:2

5/35

cfu/

mL

bid

days

1-14

clarit

hrom

ycin

500

mg

bid,

ass

oci

ated

adv

erse

tabl

etco

unt;

Dur

ing

treat

men

tna

usea

(10%

vs36

.6%

;RR

Mea

nage

:40

y(G

iflorex

,Erre

kapp

atin

idaz

ole

500

mg

bid

effe

cts

and

treat

men

tUB

T(at

6w

k)0.

3,95

%CI

0.1

to0.

9);ta

ste

dist

urba

nce

H.py

lori

posit

ive,

Euro

tera

pici

S.p.

A,da

ys1-

7to

lera

bility

(23.3%

vs50

%;R

R0.

5,95

%CI

0.2

to0.

9);he

alth

y,M

ilan,

Italy)

Seco

ndar

y:era

dica

tion

diar

rhea

(3.3%

vs26

.6%

;RR

0.1,

95%

CI0.

1asy

mpt

omat

icra

teto

0.9)

Follo

win

gtre

atm

ent

nosi

gnific

antd

iffer

ence

betw

een

grou

psAd

here

nce:

100%

Erad

icatio

n:83

.3%

vs80

%(p

=N

S)Cr

emon

ini

N=

97UB

TG

roup

1:R

abep

razo

le20

mg

bid,

Prim

ary:

antib

iotic

-Qu

estio

nnair

e;Sy

mpt

oms:

(2002

)13M

/F:4

3/54

Lact

obac

illus

GG

bid

clar

ithro

myc

in50

0m

gass

oci

ated

adv

erse

tabl

etco

unt;

Durin

gtre

atm

ent

tast

edi

stur

banc

e(G

roup1

=

Mea

nage

:not

(Giflo

rex,E

rreka

ppa

bid,

tinid

azol

e50

0m

gbi

deffe

cts

and

treat

men

tUB

T(at

5-7

wk)

9.5%

,Gro

up2

=5%

,Gro

up3

=5%

,Gro

up4

=

prov

ided

Euro

tera

pici

S.p.

A,da

ys1-

7to

lera

bility

40%

;RR

0.15

,95%

CI0.

05to

0.46

);dia

rrhea

H.py

lori

posit

ive,

Mila

n,Ita

ly)Se

cond

ary:

era

dica

tion

(Grou

p1=

5%,G

roup

2=

5%,G

roup

3=

5%,

heal

thy,

Gro

up2:

rate

Gro

up4

=30

%;R

R0.

16,9

5%CI

0.04

to0.

56)

asy

mpt

omat

icSa

cchr

omyc

esbo

ular

dii

Follo

win

gtre

atm

ent

nosi

gnific

antd

iffer

ence

bid

(Cod

ex,S

mith

Klin

ebe

twee

ngr

oups

Beec

ham

,Mila

n,Ita

ly)Ad

here

nce:

notr

epo

rted

Gro

up3:

Erad

icatio

n:G

roup

1=

76%

,Gro

up2

=81

%,

Lact

obac

illus

acid

ophi

lus

Gro

up3

=86

%,G

roup

4=

80%

(p=

NS)

and

Bifid

obac

teriu

mla

ctis

bid

(Ferz

ym,

Spec

chia

sol,M

ilan,

Italy)

Gro

up4:

plac

ebo

bid

Allg

roup

sgi

ven

treat

men

ton

days

1-14

Myll

yluom

aN

=47

Sero

logy

;UBT

Lact

obac

illus

GG

,La

nsop

razo

le30

mg

bid,

Prim

ary:

antib

iotic

-Qu

estio

nnair

e;Sy

mpt

oms:

no

sign

ifican

tdiff

eren

cein

any

(2005

)14M

/F:1

8/29

Prop

ioni

bact

eriu

mcla

rithr

omyc

in50

0m

gbi

d,ass

oci

ated

adv

erse

tabl

etco

unt;

adv

erse

effe

cts

Mea

nage

:55.

6y

freud

enre

ichiis

sp.

am

oxi

cillin

1g

bid

days

effe

cts

and

treat

men

tUB

T(at

4w

k);Ad

here

nce:

notr

epo

rted

H.py

lori

posit

ive,

sher

man

ii,L.

rham

nosu

s,1-

7to

lera

bility

sero

logy

(at4

mo)

Erad

icatio

n:91

%vs

79%

(p=

0.42

)he

alth

y,Bi

fidob

acte

rium

brev

eSe

cond

ary:

era

dica

tion

asy

mpt

omat

ic1

10

9cf

u/m

Lbi

dfo

r7ra

teda

ys,t

hen

daily

for2

1da

ys(m

ilk-ba

sedf

ruit

drin

k;Va

lioLt

d.,H

elsi

nki,

Finl

and)

Nis

taN

=11

4UB

TBa

cillu

scla

usii2

10

9R

abep

razo

le20

mg

bid,

Prim

ary:

antib

iotic

-Si

deeffe

ctdi

ary/

Sym

ptom

s(IT

T):n

ause

a(25

.9%vs

50%

;RR

(2004

)15M

/F:5

5/59

cfu/

mL

tidda

ys1-

14cla

rithr

omyc

in50

0m

gbi

d,ass

oci

ated

adv

erse

ques

tionn

aire

;0.

519,

95%

CI0.

31to

0.88

),dia

rrhea

(9.3%

vsM

ean

age

:(E

nterog

ermina

,San

ofi-

am

oxi

cillin

1g

bid

days

effe

cts

and

treat

men

tvi

alco

unt;

UBT

30.8

%;R

R0.

301,

95%

CI0.

12to

0.76

),tre

atm

entg

roup

Synt

hela

boO

TC,M

ilan,

1-7

tole

rabi

lity(at

6w

k)ep

igas

tricp

ain

(44.4%

vs65

.4%

;RR

0.68

,95%

46y,

Italy)

Seco

ndar

y:era

dica

tion

CI0.

48to

0.97

)pl

aceb

ogr

oup

rate

Adhe

renc

e:notr

epo

rted

43y

Erad

icatio

n:72

.2%

vs71

.15%

(p=

NS)

H.py

lori

posit

ive,

asy

mpt

omat

ic

ITT

=in

tent

ion

totre

at;N

S=

nots

igni

fican

t;UB

T=

13C-

urea

brea

thte

st.


significantly differ between the groups (91% vs 79%; p =0.42).

In an intention-to-treat analysis in the fourth trial, 114patients were administered B. clausii or placebo on days 1-14 and triple antibiotic therapy on days 1-7.15 The probioticimproved nausea (25.9% vs 50%; RR 0.519; 95% CI 0.31to 0.88), diarrhea (9.3% vs 30.8%; RR 0.301; 95% CI 0.12to 0.76), and epigastric pain (44.4% vs 65.4%; RR 0.68;95% CI 0.48 to 0.97); however, it had no effect on tastedisturbance (53.7% vs 59.6%; RR 0.901; 95% CI 0.65 to1.26) during the first week while patients were receivingantibiotic therapy. The probiotic continued to improve nau-sea during week 2 (14.8% vs 32.7%; RR 0.453; 95% CI0.21 to 0.96). However, this probiotic did not improveeradication rates (72.2% vs 71.15%; p = NS).

Discussion

The majority of the studies on probiotic therapy during H.pylori eradication did not have strong designs. To evaluatethe most robust data, only randomized, double-blind, place-bo-controlled trials of probiotics and H. pylori eradicationtherapy were included in this review. In 3 of the 4 trials, pro-biotics increased tolerability and reduced adverse effects, par-ticularly nausea, taste disturbance, diarrhea, and epigastricpain, of H. pylori eradication therapy.12,13,15 This was true of avariety of probiotic strains such as Lactobacillus spp., Sac-chromyces spp., Bifidobacterium spp., and B. clausii. One tri-al did not find a reduction in adverse effects; however, it wasthe smallest of the 4 trials and the only one to use a milk-based probiotic supplement.14 Probiotics did not appear tohave an effect on the eradication rates in any of the 4 trials.

Strengths of the 4 trials consist of the use of objectivedata such as the urea breath test and serologic assays suchas the enzyme-linked immunosorbent assay to diagnose H.pylori in healthy, asymptomatic study subjects. The ureabreath test has an excellent positive and negative predictivevalue, regardless of H. pylori prevalence. Although quanti-tative antibody testing has very good negative predictivevalue, the positive predictive value depends on H. pyloriprevalence, and is not recommended for use after therapy.The urea breath test and serology were used to confirmeradication between 4 and 7 weeks after eradication thera-py, which adds a limitation to the trials with the use ofserologic assays after treatment, but are still consideredvalid objective measurements in clinical trials. The first tri-al used specific and detailed questionnaires to assess symp-toms, and patients were also provided verbal and printedinstructions on filling in the questionnaires.12 This mostlikely led to increased questionnaire adherence and relia-bility of the adverse effect data. The second trial includedasymptomatic subjects and used a mandatory run-in periodto prevent a confounding factor of previous gastrointestinalsymptoms.13 Myllyluoma and colleagues used fecal recov-

ery of Lactobacillus and Propionibacterium to show ad-herence in the treatment group and probiotic abstinence inthe placebo group.14 The first and fourth trials analyzedsymptoms individually, and categorized them weekly.12,15This provided specific information regarding adverseevents and effective timing of probiotics.

Even though these are well-designed trials, they do havelimitations. They used differing eradication regimens. Twoof the trials12,13 used a tinidazole-based regimen, which isnot considered first-line therapy in the US.3 All 4 trialsused a 7-day eradication regimen, which is shorter than therecommended 10- to 14-day regimens3; this may have hadan effect on eradication rates and tolerability. Small samplesizes further limited the studies. In addition, subjects com-pleted questionnaires and symptom diaries to report ad-verse effects and treatment tolerability, which may haveskewed the results because of the subjective nature of ad-verse effect reporting, and the inevitable variability in pa-tient response to adverse effects. While all 4 trials assessedadherence, rates were not reported. This may be an issuebecause of the high pill burden of H. pylori eradicationtherapy with additional probiotic doses. One trial includedparticipants from a group of educated health-careproviders, which does not necessarily represent the popula-tion most affected by H. pylori disease.12 Adverse effectsmight be tolerated differently in this population, and the di-ets of the participants may be more rich in fruits, vegeta-bles, and dairy compared to subjects in other trials. Noneof the studies controlled for subjects intake of dietary pro-biotics such as yogurt or other probiotic supplements. It isunclear whether any geographic differences existed, sincethe 3 trials that showed improvement in tolerability wereconducted in Italy,12,13,15 whereas the fourth trial was con-ducted in Finland.14 Finally, all trials used different probi-otics.

Conflicting evidence exists regarding the efficacy ofprobiotics for the reduction of adverse effects and increasein tolerability of H. pylori eradication therapies. Some tri-als indicate that probiotics are effective for reducing ad-verse effects and increasing eradication rates of H. pyloritherapy.16,17 Other trials showed increased eradication rates,with increases or no change in adverse effects.18,19 Whilesome trials report probiotics have no effect on adverse ef-fects or eradication rates,20,21 others report that probioticsreduce adverse effects without affecting eradication rates.22

Probiotics may have a role as adjunctive therapy for H.pylori eradication. They have been shown to improve gas-trointestinal adverse effects such as nausea, taste distur-bance, diarrhea, and epigastric discomfort. By reducing theadverse effects, patients may adhere to H. pylori eradica-tion therapy, thereby increasing eradication rates. This issupported by a study that showed the use of a yogurt probi-otic preparation resulted in a higher completion rate thaneradication therapy alone.17 An increase in the eradication

Probiotics as Adjunctive Therapy for H. pylori

The Annals of Pharmacotherapy n 2011 July/August, Volume 45 n 963theannals.comCopyrighted material. Reproduo proibida.

rate of H. pylori during antibiotic therapy may decrease thechance of recurrence and may result in reduced bacterialresistance.

Probiotics are not often used as adjunctive therapy forpatients with H. pylori infections. This provides the phar-macist with an important role in discussing the option ofprobiotic use in combination with H. pylori eradicationtherapy. A pharmacist should, however, take into accountthe economic burden of these products before recommend-ing them. A typical regimen of probiotics would begin inconjunction with the H. pylori eradication therapy and maybe continued for a week following completion of the eradi-cation therapy. Many probiotics are readily available in thecommunity, and choosing an appropriate product could bean important factor in treating the patient. Unfortunately,the products used in these studies are not typically sold inthe US, which makes selecting a probiotic supported byevidence difficult. Even though a specific strain of Lacto-bacillus supported by evidence may not be available in theUS, it may be reasonable to extrapolate the effects of thatstrain to other types of Lactobacillus when product selec-tions are limited. Table 3 contains a noninclusive list ofprobiotic preparations available in the US.

Probiotics are most commonly recommended for use onan outpatient basis to healthy patients without many co-morbid conditions. This population represents most of thepatients in the clinical trials that were reviewed. Probioticsare freely used because of their dietary supplement status,which limits the amount of safety data reported, and also be-cause of their perceived lack of serious complications. How-ever, there have been case reports of fungemias caused bySaccharomyces cerevisiae and S. boulardii with and withoutprobiotic supplementation.23 Patients who acquire invasiveSaccharomyces infections have at least one risk factor, in-cluding intravenous catheter use, intensive care unit hospital-

ization, and immunocompromised status. There have beenother case reports linking Lactobacillus spp. and Bacillussubtilis to invasive bacterial infections in patients taking pro-biotic supplements.24-26 This is contradictory to clinical trialsshowing Lactobacillus to be safe for use in immunocompro-mised populations, but is still an alarming finding. This maybe important to consider when recommending probiotics topatients who might be at a higher risk of acquiring blood-borne infections, especially the immunocompromised or pa-tients with central catheters.

Summary

Probiotics may be beneficial in reducing adverse effectsand increasing tolerability of H. pylori eradication regi-mens. They may especially be helpful in patients with re-current H. pylori and history of gastrointestinal adverse ef-fects with antibiotics. Pharmacists can play an importantrole in educating their patients regarding probiotic use dur-ing H. pylori eradication therapy.

Sheila M Wilhelm PharmD BCPS, Assistant Professor, WayneState University, and Harper University Hospital, Detroit, MIJennifer L Johnson PharmD, PGY 1 Resident, Harper UniversityHospitalPramodini B Kale-Pradhan PharmD, Associate Professor, WayneState University; and St. John Hospital and Medical Center, Detroit,MICorrespondence: Dr. Kale-Pradhan, [email protected]/Online Access: www.theannals.com/cgi/reprint/aph.1Q104Conflict of interest: Authors reported none

References1. Valle JD. Peptic ulcer disease and related disorders. In: Fauci AS, Braun-

wald E, Kasper DL, et al., eds. Harrisons principles of internal medicine.17th ed. New York, NY: McGraw-Hill Companies, Inc., 2008:1855-71.


SM Wilhelm et al.

Table 3. Noninclusive List of Available Probiotics in the USCost Capsules

Product Manufacturer Probiotic CFU (US $) (n)Align Procter and Gamble Bifidobacterium infantis 35624 (bifantis) 1 109 27.99 28Culturelle Amerifit Brands Lactobacillus GG, inulin 1 1010 24.99 30Flora Q Kenwood Therapeutics Lactobacillus acidophilus Not stated 29.99 30

BifidobacteriumLactobacillus paracaseiStreptococcus hermophilus

Floranex Rising L. acidophilus 2 106 11.99 50Lactobacillus bulgaricus

Florastor Biocodex Saccharomyces boulardii Not stated 46.99 5011.99 10

Lactinex (refrigerated) Becton, Dickinson, and Co. L. acidophilus 1 108 13.99 12 (packets)L. bulgaricus

Phillips Colon Health Bayer L. acidophilus 1.5 109 15.99 30Bifidobacterium bifidumBifidobacterium longum

Systenex Ganeden Biotech Bacillus coagulans (GanedenBC) 2 109 16.99 30


2. Barkun A, Leontiadis G. Systematic review of the symptom burden,quality of life impairment and costs associated with peptic ulcer disease.Am J Med 2010;123:358-66.e2.

3. Chey WD, Wong BC. American College of Gastroenterology guidelineon the management of Helicobacter pylori infection. Am J Gastroenterol2007;102:1808-25.

4. Jarosz M, Rychlik E, Siuba M, et al. Dietary and socio-economic factorsin relation to Helicobacter pylori re-infection. World J Gastroenterol2009;15:1119-25.

5. Starzynska T, Malfertheiner P. Helicobacter and digestive malignancies.Helicobacter 2006;11(suppl 1):32-5.

6. Rauws EA, Tytgat GN. Cure of duodenal ulcer associated with eradica-tion of Helicobacter pylori. Lancet 1990;335:1233-5.

7. Gotteland M, Brunser O, Cruchet S. Systematic review: are probioticsuseful in controlling gastric colonization by Helicobacter pylori? Ali-ment Pharmacol Ther 2006;23:1077-86.

8. Tong JL, Ran ZH, Shen J, Zhang CX, Xiao SD. Meta-analysis: the effectof supplementation with probiotics on eradication rates and adverseevents during Helicobacter pylori eradication therapy. Aliment Pharma-col Ther 2007;25:155-68.

9. Cremonini F, Di Caro S, Nista EC, et al. Meta-analysis: the effect of pro-biotic administration on antibiotic-associated diarrhoea. Aliment Phar-macol Ther 2002;16:1461-7.

10. Kale-Pradhan PB, Jassal HK, Wilhelm SM. Role of Lactobacillus in theprevention of antibiotic-associated diarrhea: a meta-analysis. Pharma-cotherapy 2010;30:119-26.

11. McFarland LV. Meta-analysis of probiotics for the prevention of antibiot-ic associated diarrhea and the treatment of Clostridium difficile disease.Am J Gastroenterol 2006;101:812-22.

12. Armuzzi A, Cremonini F, Bartolozzi F, et al. The effect of oral adminis-tration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Aliment Pharma-col Ther 2001;15:163-9.

13. Cremonini F, Di Caro S, Covino M, et al. Effect of different probioticpreparations on antiHelicobacter pylori therapyrelated side effects: aparallel group, triple blind, placebo-controlled study. Am J Gastroenterol2002;97:2744-9.

14. Myllyluoma E, Veijola L, Ahlroos T, et al. Probiotic supplementation im-proves tolerance to Helicobacter pylori eradication therapya placebo-controlled, double-blind randomized pilot study. Aliment PharmacolTher 2005;21:1263-72.

15. Nista EC, Candelli M, Cremonini F, et al. Bacillus clausii therapy to re-duce side-effects of antiHelicobacter pylori treatment: randomized,double-blind, placebo controlled trial. Aliment Pharmacol Ther 2004;20:1181-8.

16. Sheu BS, Cheng HC, Kao AW, et al. Pretreatment with Lactobacillus-and Bifidobacterium-containing yogurt can improve the efficacy ofquadruple therapy in eradicating residual Helicobacter pylori infectionafter failed triple therapy. Am J Clin Nutr 2006;83:864-9.

17. Sheu BS, Wu JJ, Lo CY, et al. Impact of supplement with Lactobacillus-and Bifidobacterium-containing yogurt on triple therapy for Helicobacterpylori eradication. Aliment Pharmacol Ther 2002;16:1669-75.

18. Canducci F, Armuzzi A, Cremonini F, et al. A lyophilized and inactivat-ed culture of Lactobacillus acidophilus increases Helicobacter pylorieradication rates. Aliment Pharmacol Ther 2000;14:1625-9.

19. Kim MN, Kim N, Lee SH, et al. The effects of probiotics on PPI-tripletherapy for Helicobacter pylori eradication. Helicobacter 2008;13:261-8.

20. Cindoruk M, Erkan G, Karakan T, Dursun A, Unal S. Efficacy and safetyof Saccharomyces boulardii in the 14-day triple antiHelicobacter pyloritherapy: a prospective randomized placebo-controlled double-blindstudy. Helicobacter 2007;12:309-16.

21. Szajewska H, Albrecht P, Topczewska-Cabanek A. Randomized, double-blind, placebo-controlled trial: effect of Lactobacillus GG supplementa-tion on Helicobacter pylori eradication rates and side effects during treat-ment in children. J Pediatr Gastroenterol Nutr 2009;48:431-6.

22. Hurduc V, Plesca D, Dragomir D, Sajin M, Vandenplas Y. A randomized,open trial evaluating the effect of Saccharomyces boulardii on the eradi-

cation rate of Helicobacter pylori infection in children. Acta Paediatr2009;98:127-31.

23. Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection:a comprehensive review. Clin Infect Dis 2005;41:1559-68.

24. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical prac-tice: what are the risks? Am J Clin Nutr 2006;83:1256-64; quiz 446-7.

25. Salminen MK, Tynkkynen S, Rautelin H, et al. The efficacy and safety ofprobiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diar-rhea in HIV patients on antiretroviral therapy: a randomized, placebo-controlled, crossover study. HIV Clin Trials 2004;5:183-91.

26. Wolf BW, Wheeler KB, Ataya DG, Garleb KA. Safety and tolerance ofLactobacillus reuteri supplementation to a population infected with thehuman immunodeficiency virus. Food Chem Toxicol 1998;36:1085-94.

El rol de los Probiticos Como Terapia Adyuvante ParaHelicobacter pyloriSM Wilhelm, JL Johnson, y PB Kale-Pradhan

Ann Pharmacother 2011;45:960-6.

EXTRACTO

OBJETIVO: Revisar la literatura concerniente al rol de los agentesprobiticos en el tratamiento de infecciones con Helicobacter pylori(HP).FUENTE DE DATOS: Se realiz una bsqueda de la literatura en la base dedatos MEDLINE (1966marzo 2011) utilizando los trminosHelicobacter pylori, probitico, Lactobacillus, Bifidobacterium,Saccharomyces, Bacillus clausii, y Propionibacterium. Se revisaron lasreferencias para identificar artculos y extractos relevantes adicionales.SELECCIN DE ESTUDIOS Y EXTRACCIN DE DATOS: Se evaluaron todos losartculos publicados en el idioma ingls. En la revisin se incluyestudios aleatorios, doble ciegos, controlados con placebo que evaluaronel uso de probiticos combinados con tratamientos estandarizados paraerradicacin de HP.SNTESIS DE DATOS: Este artculo repasa la evidencia relacionada con eluso de probiticos como terapia adyuvante para HP. Varios probiticos,incluyendo Lactobacillus spp, Saccharomyces spp., Bifidobacteriumspp., y Bacillus clausii reducen efectos adversos tales como nusea,alteracin del sentido del gusto, diarrea y dolor epigstrico y aumenta latolerancia a los tratamientos para erradicar HP. Segn los estudiosrevisados, los probiticos no alteran la tasa de erradicacin de HP.CONCLUSIONES: Los probiticos pueden ser de beneficio en el tratamientopara erradicar HP al reducir los efectos adversos y aumentar la toleranciaal tratamiento. Los probiticos pueden ser considerados para pacientesque estn recibiendo tratamiento para erradicar HP y para pacientes conHP recurrente e historial de efectos adversos relacionados al tratamientocon antibiticos. Los farmacuticos pueden jugar un papel importante enla educacin de pacientes en el uso de probiticos durante la terapia deerradicacin de HP.

Traducido por Astrid J Garca-Ortiz

Traiter les Bactries par des Bactries: Le Rle des ProbiotiquesComme Traitement Adjuvant de lHlicobacter pyloriSM Wilhelm, JL Johnson, y PB Kale-Pradhan

Ann Pharmacother 2011;45:960-6.

RSUMOBJECTIF: Revoir la documentation scientifique sur le rle desprobiotiques pour le traitement des infections Hlicobacter pylori(HP).SOURCES DE DONNES: La recherche de la documentation scientifique at effectue par le biais de MEDLINE (1966-Mars 2011) avec les

Probiotics as Adjunctive Therapy for H. pylori

The Annals of Pharmacotherapy n 2011 July/August, Volume 45 n 965theannals.comCopyrighted material. Reproduo proibida.


SM Wilhelm et al.

termes Hlicobacter pylori, probiotique, Lactobacillus, Bifidobacterium,Saccharomyces, Bacillus clausii, et Propionibacterium. Les articles derfrences ont t revus afin de dceler dautres articles et rsumspertinents.SLECTION DES TUDES ET EXTRACTION DES DONNES: Tous les articlespublis de langue anglaise ont t valus. Les tudes randomises, double insu avec un contrle placebo valuant lutilisation deprobiotiques combins un traitement standard pour lradication delinfection HP chez les adultes ont t inclues dans la revue.SYNTHSE DES DONNES: Cette article revoit les donnes concernantlutilisation des probiotiques pour le traitement adjuvant du HP. Unevarit de probiotiques incluant Lactobacillus spp., Saccharomyces ssp., etBacillus clausii reduisent les effets indsirables tels que les nauses,laltration du got, les diarrhes et la douleur gastrique et amliore la

tolrance au traitement pour lradication du HP. Selon les tudes rvises,les probiotiques ne compromettent pas les taux dradication du HP.CONCLUSIONS: Lutilisation des probiotiques pourrait tre bnfique pourrduire les effets indsirables et augmenter la tolrance au traitement lorsde lutilisation de traitements pour radiquer le HP. Les probiotiquespourraient tre considrs pour lemploi lorsque les patients utilisent untraitement pour radiquer le HP. Les probiotiques pourraient tre utilesspcialement chez les patients qui ont une histoire de rcurrencedinfection HP et des effets indsirables documents avec lesantibiotiques. Les pharmaciens pourraient jouer un rle important danslducation de ces patients concernant lutilisation de probiotiquesdurant leur traitement pour liminer le HP.

Traduit par Chantal Guvremont

Articles published in The Annals Are posted in The Annals Online and indexed in PubMed weeks before appearing in print. Appear on the prestigious HighWire Press platform at Stanford University, host to the most

frequently cited journals. Permit readers to access citations to other HighWire journals through free full-text access links. Receive extensive peer review and contribute to The Annals high journal impact factor.

Authors publishing in The Annals realize these additional benefits Quick and easy online manuscript submission for faster turnaround. No submission fees or page charges. And more: visit www.theannals.com and select Author Information.


Documents

Enterogermina Wilhelm 2011