-IBS RFAXIMIN UPDATES.

1. ‹#›

2. ‹#›
RIFAXIMIN- USAGE
INTESTINAL BACTERIAL INFECTIONS
HEPATIC ENCEPHALOPATHY
DIVERTICULAR DISEASE
SMALL INTESTINE BACTERIAL OVERGROWTH
IRRITABLE BOWEL SYNDROME
IBD (Crohn’s disease)
WHENEVER AN ANTIMICROBIAL IS REQUIRED FOR TREATING DISEASES AND CONDITIONS
WITHIN THE GASTROINTESTINAL TRACT

3. ‹#›
IBS
Irritable Bowel Syndrome

4. ‹#›
ROME III DIAGNOSTIC CRITERIA ROME II DIAGNOSTIC CRITERIA
C. Functional Bowel Disorders C. Functional Bowel Disorders
C1. Irritable Bowel Syndrome
Diagnostic criterion*
Recurrent abdominal pain or discomfort** at least 3
days/month in last 3 months associated with two or more
of the following:
1. Improvement with defecation
2. Onset associated with a change in frequency of stool
3. Onset associated with a change in form (appearance)
of stool
* Criterion fulfilled for the last 3 months with symptom
onset at least 6 months prior to diagnosis
**“Discomfort” means an uncomfortable sensation not
described as pain. In pathophysiology research and clinical
trials, a pain/discomfort frequency of at least days a
week during the screening evaluation is recommended for
subject eligibility.
C1. Irritable Bowel Syndrome
At least 12 weeks, which need not be consecutive, in the
preceding 12 months of abdominal discomfort or pain that
has two out of three features:
1. Relieved with defecation; and/or
2. Onset associated with a change in frequency of stool;
and/or
3. Onset associated with a change in form (appearance)
of stool.
Symptoms that Cumulatively Support the Diagnosis of
Irritable Bowel Syndrome
– Abnormal stool frequency;
-– Abnormal stool form (lumpy/hard or loose/ watery
stool);
-– Abnormal stool passage (straining, urgency, or feeling of
incomplete evacuation);
-– Passage of mucus;
-– Bloating or feeling of abdominal distension.

5. ‹#›
IBS SUBTYPING – ROME III
0 25 50 75 100
0
25
50
75
100
% loose or watery stools
%
hard
or
lumpy
stools
IBS-U
IBS-C IBS-M
IBS-D
1. IBS with constipation (IBS-C): hard or lumpy stools ≥ 25% and loose
(mushy) or watery stools < 25% of bowel movements.
2. IBS with diarrhea (IBS-D): loose (mushy) or watery stools
≥ 25% and hard or lumpy stool <25% of bowel movements.
3. Mixed IBS (IBS-M): hard or lumpy stools ≥25%
and loose (mushy) or watery stools ≥25% of
bowel movements.
4. Unsubtyped IBS (IBS-U): insufficient
abnormality of stool consistency to
meet criteria for IBS-C, D, or M.
Longstreth et al. Gastroenterology 2006.

6. ‹#›
Adapted from Wells Aliment Pharmacol Ther 1997.
IMPACT OF IBS ON QUALITY OF LIFE
30
40
50
60
70
80
90
Mean
SF-36
score
US Norm
Diabetes type II
IBS
Clinical
depression
Role-
Physical
Bodily Pain
Vitality Social
Functioning
Role-
Emotional
Mental
Health
General
Health
Physical
Functioning
100

7. ‹#›
Abdominal pain/discomfort
 Antispasmodics
 Tricyclic antidepressants
Abdominal
pain/
discomfort
STANDARD IBS THERAPIES ONLY TREAT INDIVIDUAL SYMPTOMS
Bloating/
distension
Bloating and distension
 Dietary modifications
 Antispasmodics
 Antiflatulents
 Digestive enzymes
Constipation
Diarrhea
Constipation
 Fiber
 Laxatives
Diarrhea
 Loperamide
 Cholestyramine

8. ‹#›
Gastrointestinal dysmotility
Visceral hypersensitivity
Brain-gut
axis
dysfunction
Psychosocial/psychosomatic factors
Parkes AmJGastroenterol 2008
Low-grade inflammation
Mucosal immune activation
Altered intestinal microbiota

9. ‹#›
IRRITABLE BOWEL SYNDROME (IBS) NOTES
Bacterial metabolism, by carbohydrate
fermentation, is the major source of intestinal
gas [hydrogen (H2), carbon dioxide (CO2), and
methane (CH4)]
Symptoms related to excessive amount of gas in
the bowel are very frequent complaints of
patients with functional bowel disorders

10. ‹#›
Evidence for gut microbes playing a role in the pathogenesis of IBS is convincing
and is supported by three main lines of reasoning:
2. Alteration of gut microbiota in IBS patients
1. A cause effect relationship documented in PI-IBS*
3. IBS symptoms are improved by treatments targeting
at gut microbiota (antibiotic, probiotics, prebiotics)
Salonen Microbiology 2010
GUT MICROBIOTA AND IBS
*PI-IBS: Post Infectious IBS

11. ‹#›
A CAUSE EFFECT RELATIONSHIP DOCUMENTED IN PI-IBS
Alteration in GI microbiota dos not inevitably lead to
IBS but may lead to chronic symptoms in susceptible
individuals
Establishment of a
dysbiosis
Activation of immune
system
Gastroenteritis may lead to an
increased risk of developing IBS
Parkes AmJGastroenterol 2008
13

12. ‹#›
Tornblom et al. 2007
Spence and Moss-Morris, 2007
Ruigomez et al. 2007
Thabane et al. 2007
Marshall et al. 2006
Mearin et al. 2005
Dunlop et al. 2003
Spiller et al. 2000
Garcia Rodriguez et al. 1999
Gwee et al. 1999
Neal et al 1997
The occurrence of PI-IBS has been documented in several studies
The overall risk for the development of IBS was increased six-fold following an episode of
bacterial GI with younger subjects, those who have prolonged fever during the episode and those
who suffer from anxiety or depression being at greatest risk.
These observations indicate a relationship between perturbations of
the microbiota, mucosal inflammation and IBS
Quigley TherAdvGastroenterol 2009
A CAUSE EFFECT RELATIONSHIP DOCUMENTED IN PI-IBS
Alteration in GI microbiota dos not inevitably lead to IBS but may lead to
chronic symptoms in susceptible individuals

13. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
Disturbed
flora
Susceptible
host
Inflammatory
response
SYMPTOMS
Quigley Ther Adv Gastroenterol 2009 16

14. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
Altered microbiota in
the small intestine
Altered microbiota in
the colon or feces
SIBO
Lee and Tack NeurogastroenterolMotil 2010
Qualitative and quantitative changes
Microbial composition or the species of predominat bacteria in the colon or feces appears to
be more relevant in IBS than the total number of microbiota

15. ‹#›
THE RELATIONSHIP AMONG SIBO AND IBS
Prevalence of SIBO in IBS using
breath test
Mild increase in small bowel bacteria, but
not classical overgrowth detected in IBS pts
-40
60
LBT GBT >100.000CFU/ml >5.000CFU/ml
%
Controls(n=42)
Author n. pts Prev. (%)
Galatola, 1995 80 56
Pimentel, 2000 202 76
Pimentel, 2003 111 57-84
Nucera, 2004 200 75
Nucera, 2005 98 65
Lupascu, 2005 65 31
Walters, 2005 39 10
Majewski, 2007 204 46
Peralta, 2009 97 56
Posserud Gut 2007

16. ‹#›
THE RELATIONSHIP AMONG SIBO AND IBS
320 patients (GI endoscopy)
SIBO tested by jejunal aspiration
112 IBS+
(35%)
SIBO +
37%
A strong association of SIBO with IBS is found at any cut-off
Age and diarrhea were positively linked with SIBO in IBS pts
42 SIBO+
37.5%
IBS +
68%
cut-off 105
258 non-SIBO
IBS=27.1%
Pyleris DigDisSci 2012

17. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
Altered microbiota in the colon or feces
Microbial composition or the species of predominat bacteria in the colon or feces appears to
be more relevant in IBS than the total number of microbiota
Technique Method Advantage Disadvantage
Culture Bacteria grown on selective
mediums
Cheap, widely available, and
easy to use
Grossly underestimates
fecal populations
PCR-T/DGGE
denaturing/
temperature gradient
gel electrophoresis
Using either temperature or a
denaturing agent to separate
DNA strands, which are then
run on a gel
Very useful in detecting
difference in bacterial
populations
Does not identify bacteria
unless bands on the gel are
cut out and sequenced
FISH (fluorescent in
situ hybridization)
Oligonucleotide probes
designed to hybridize with
specific species
Allows spatial organization of
microbiota to be studied
Slow, will only detect the
bacteria probed for
Quantitative PCR Specific primers detect either
individual species or genus
Can detect small number of
bacteria and quantify them
Laborious
16S rDNA sequencing Bacterial DNA isolated and
ribosomal DNA cloned and then
sequenced
Enormous quantities of data at
individual species level
Very costly, available in
only a few specialist
centers
Parkes AmJGastroenterol 2008 20

18. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
Reference No. IBS patients Method Outcome
Si et al.19 (2004) Unsubtyped IBS
(n = 25)
Culture Bifidobacteria and Enterobacteriaceae in IBS
patients
Matto et al.20 (2005) IBS-D (n = 12)
IBS-C (n =9)
Culture Coliforms and aerobic bacteria/total bacteria in IBS
patients
IBS-M (n =5) PCR-DGGE Clostridium and Eubacterium in IBS patients
Malinen et al.22
(2005)
IBS-D (n = 12)
IBS-C (n =9)
qPCR Lactobacillus in IBS-D patients and Veillonella in IBS-
C patients
IBS-M (n =6)
Maukonen et al.23
(2006)
IBS-D (n =7)
IBS-C (n =6)
IBS-M (n =3)
PCR-DGGE
RT-PCR-DGGE
Clostridium coccoides-Eubacterium rectale in IBS-C
patients
Kassinen et al.24
(2007)
IBS-D (n = 10)
IBS-C (n =8)
IBS-M (n =6)
qPCR
with nucleic acid
fractionation
Collinsella, Clostridium, and Coprococcus species in
IBS patients
Kerckhoffs et al.25
(2009)
IBS-D (n = 14)
IBS-C (n = 11)
IBS-M (n = 16)
FISH Bifidobacterium in IBS patients
Tana et al.4 (2010) IBS-D (n =8) Culture Lactobacillus in IBS patients
IBS-C (n = 11) qPCR Veillonella in IBS patients
IBS-M (n =7)
Lee and Tack NeurogastroenterolMotil 2010

19. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
Common Traits
( Decrease Lactobacillus in D-IBS)
 Increase Veillonella in C-IBS
 Decrease in Bifidobacterium in IBS
Dietary factors, different techniques
and experimental design
may explain the different results
Lee and Tack NeurogastroenterolMotil 2010; Quigley TherAdvGastroenterol 2009
IBS patients, regardless of sub-type, do exhibit a fecal flora
that is clearly different from control subjects

20. ‹#›
ALTERATION OF GUT MICROBIOTA IN IBS PATIENTS
The link between Microbiota and IBS symptoms
Bacterial fermentation of undigested carbohydrate leads
to short-chain fatty acids (SCFAs) production , with the
gases like CO2, H2 and CH4 created as by products
Total excretion of gas may be not different in
IBS patients from healthy controls, but IBS
patients might have poor tolerance to
moderate gas load
Salonen Microbiology 2010; Serra NeurogastroeneteolMotil 2010; Tana NeurogastroeneteolMotil 2010
Bloating and flatulence
The high level of SCFA affect visceral sensation
and correlate with abdominal pain, bloating,
anxiety and poor quality of life
Acetate (a SCFA) is a known chemical irritant
Pain and anxiety

21. ‹#›
TARGETING GUT MICROBIOTA: ANTIBIOTIC
Disease Design Patients Daily dose (days)
Evaluation
criteria
Overall
assessment
Pimentel et al,
2011, NEJM
IBS without
constipation
Double blind
vs. placebo
Rif 624
Pla 634
550 mg x 3 (84 – 3
months)
IBS symptoms, IBS
related bloating
E: Rif  Pla
T: Rif  Pla
Cappello, 2005
Dig Liver Dis
Lactose
intolerant
patients
Double-blind
placebo, open
control with
diet
Rif 14
Pla 5
Diet 13
200 mg x 2 (10) H2 breath test,
symptom score
E:  Diet >Pla
Pimentel, 2006
Annals Int Med
IBS Double-blind
vs placebo
Rif 43
Pla 44
400 mg x 3 (10) H2 breath test, IBS
symptoms
E: Rif  Pla
T: Rif  Pla
Sharara, 2006
Am J Gastro
Abdominal
bloating,
flatulence
Double-blind
vs. placebo
Rif 63
Pla 61
400 mg x 2 (10) H2 breath test,
symptom score
E: Rif  Pla
T: Rif  Pla
Di Stefano, 2000
Aliment.
Pharmacol. Ther.
Functional
bowel
disorders
Double-blind
Vs charcoal
Rif 18
Cha 16
400 mg x 2 (7)
400 mg x 2 (7)
H2 breath test,
intestinal gas
production-related
symptoms
E: Rif  Cha
T: Rif  Cha
Low et al, 2010,
J Clin
Gastroenterol
IBS ( I) with LBT
positive for
methane
Retrospective,
comparison
with
neomycin
Rif 39
Neo 8
Rif+Neo 27
400 mg x 3 (10)
500 mg x 2 (10)
400 mg x 3 + 500 mg
x2 (10)
Methane
eradication
E:Rif+Neo>
NeoRif
T: good
Peralta et al,
2009 World J
Gastroenterol,
IBS ( II) with
SIBO
Open Rif 54 400 mg x 3 (7) H2 breath test, IBS
symptoms
E: Rif  vs basal v.
T: good

22. ‹#›
Original Article
Rifaximin Therapy for Patients with Irritable Bowel
Syndrome without Constipation
Mark Pimentel, M.D., Anthony Lembo, M.D., William D. Chey, M.D., Salam Zakko, M.D., Yehuda
Ringel, M.D., Jing Yu, Ph.D., Shadreck M. Mareya, Ph.D., Audrey L. Shaw, Ph.D., Enoch
Bortey, Ph.D., William P. Forbes, Pharm.D., for the TARGET Study Group
Volume 364(1):22-32
January 6, 2011

23. ‹#›
STUDY OVERVIEW
In two trials involving patients with irritable bowel syndrome
without constipation, 2 weeks of treatment with the
minimally absorbed antibiotic rifaximin was more effective
than placebo in providing adequate relief of symptoms.

24. ‹#›
Pimentel M et al. N Engl J Med 2011;364:22-32
ENROLLMENT, RANDOMIZATION, AND FOLLOW-UP

25. ‹#›
Pimentel M et al. N Engl J Med 2011;364:22-32
END-POINTS
Primary end-point:
Self reported relief of symptoms for at least 2 of the first 4 weeks after treatment
Secondary end-point
Self reported relief of IBS-related bloating for at least 2 of the first 4 weeks after
treatment

26. ‹#›
*
p=0.0125
*
p=0.0263
*
p=0.0008
*
p=0.0045
*
p=0.0167
*
p=0.0002
* Rifaximin vs Placebo group
Pimentel M et al. N Engl J Med 2011;364:22-32
PRIMARY ENDPOINTS: RELIEF OF IBS SYMPTOMS AND BLOATING

27. ‹#›
Pimentel M et al. N Engl J Med 2011;364:22-32
ADEQUATE RELIEF OF GLOBAL IBS SYMPTOMS IN THE STUDIES COMBINED

28. ‹#›
CONCLUSIONS
Primary endpoints: A significantly greater proportion of patients achieved
adequate relief of IBS symptoms and bloating during the first 4 weeks (weeks
3–6) following the 2–week treatment period (weeks 1–2) in both studies as
well as in pooled analyses, compared with placebo.
Secondary endpoints: rifaximin significantly improved daily assessments of
IBS symptoms, bloating, abdominal pain and discomfort stool consistency
during the entire 3 months in both studies as well as in pooled analyses,
compared with placebo.
The safety profiles were similar between rifaximin and placebo.
TARGET 1 & 2:
Results of primary and secondary endpoints
Pimentel M et al. N Engl J Med 2011;364:22-32

29. ‹#›
Rifaximin dose-finding study for
the treatment of small intestinal
bacterial overgrowth
Lauritano EC et al. Aliment Pharmacol Ther 2005; 22: 31-35
33

30. ‹#›
PATIENTS AND METHODS
34
90 patients enrolled.
Rifaximin:
- 30 patients: 600 mg /day (3 daily administrations: 2 tablets – 1 tablet – 1 tablet)
- 30 patients: 800 mg /day (3 daily administrations: 2 tablets – 1 tablet – 1 tablet)
- 30 patients: 1200 mg /day (3 daily administrations: 2 tablets – 2 tablets – 2 tablets)
Duration of treatment: 7 days
Randomized prospective study
ROME II IBS patients with confirmed SIBO via glucose breath test
Lauritano et al. Alim Pharmacol Ther 2005

31. ‹#›
RESULTS
020406080
100
GlucoseBreathTestNormalization
600mg/day 800mg/day 1200mg/day
%
of
Patients
p< 0.05
No significant differences in adverse events among 3 groups
Lauritano et al. Alim Pharmacol Ther 2005
p< 0.05
ns
Eradication rates
35

32. ‹#›
CONCLUSIONS
Results from the present study show that higher doses of rifaximin (1200
mg/day) are associated with a significantly higher therapeutic efficacy in
terms of SIBO eradication.
At the tested doses, rifaximin was associated only with uncommon, mild,
transient side-effects
Lauritano et al. Alim Pharmacol Ther 2005 36

33. ‹#›
EFFICACY OF RIFAXIMIN ON SYMPTOMS
Meyrat APT 2012
010
Bloating DiarrhoeaFlatulence PainReducedwell-being
BeforeRFX Aftertreatment(2weeks)
150 IBS
patients
71% LHBT
positive
2 weeks RFX
800 mg/day
Evaluation
week 4 and 14

34. ‹#›
High-dose rifaximin treatment
alleviates global symptoms of
irritable bowel syndrome
Jolley J Clin Experiment Pharmacol 2011;4:43-48

35. ‹#›
PATIENTS AND METHODS
162 patients group A; 81 group B (Group A patients unresponsive to therapy)
Rifaximin:
- 162 patients: 1200 mg /day
- 81 patients unresponsive to 1200 mg/day: 2400 mg /day
Duration of treatment: 10 days; if non-respondent high-dose for 10 days
Retrospective study
28% D-IBS; 20% C-IBS; 24% M-IBS
56% positive H2 breath-test; 20% positive CH4 breath-test; 6% both
Jolley ClinExperimentPharmacol 2011

36. ‹#›
RESULTS
The mean percent improvement in global symptoms was similar in
patients with IBS who received rifaximin 1200 mg/day and in patients
who received subsequent high-dose rifaximin
Mean improvement of global symptoms
Jolley ClinExperimentPharmacol 2011

37. ‹#›
RESULTS
Patients with ≥50% best global improvement
Rifaximin effectively reduced IBS symptoms in patients with either
subtype. High-dose rifaximin was able to improve symptoms in patients
initially unresponsive to 1200mg/day in either subtipes.

38. ‹#›
CONCLUSIONS
Rifaximin was effective in all patients subtypes
A greater percentage of patients with diarrhea-predominant
IBS had an initial response
Patients with mixed-symptom IBS were more likely to respond
to high-dose rifaximin
In case of patients unresponsive to the currently established dosages,
an higher dosage may be suggested
However, the use of 200 mg formulation can give rise to problem of
compliance for dosages higher than 1200 mg/day
Results are in line with Pimentel’s study

39. ‹#›
EFFECTS OF RIFAXIMIN TREATMENT AND RETREATMENT IN
NONCONSTIPATED IBS SUBJECTS
Pimentel M et al. Dig Dis Sci 2011;56:2067-2072
Aim of the study: test the efficacy and durability of Rifaximin improvement
of symptoms in retreatments

40. ‹#›
EFFICACY OF RETREATMENT
More than 75% of subjects who initially responded to rifaximin experienced clinical
benefit with any retreatment.
The percentage of subjects who experienced improvement in their IBS symptoms did
not decrease with increasing number of treatments
Ten subjects already received Rifaximin without improvements. Changing the doses
resulted in improvement in nine of these subjects.

41. ‹#›
RESISTANCE IN RE-TREATMENT
54/65
38/40 17/18
6/7
3/4
Success rate of each
retreatment with Rifaximin
If resistance developed,
then it would be reasonable
to assume that subsequent
treatments would be less
and less effective.
Instead, the percentage of
subjects who responded
with increasing number of
treatments did not change
Resistance was not tested but clinical resistance can be inferred in two ways

42. ‹#›
RESISTANCE IN RE-TREATMENT
Duration of benefit
between successive
retreatments with rifaximin
If resistance developed,
then it would be reasonable
to observe a shortening of
time between visits for
retreatments.
Instead, there was no
change in the duration of
benefit (median is always 4
months minimum).

43. ‹#›
THE EFFECT OF RIFAXIMIN ON GUT FLORA AND
STAPHYLOCOCCUS RESISTANCE
Kim MS et al. Dig Dis Sci 2013;58:1676-82

44. ‹#›
STUDY DESIGN
Control
10 d
Stool and
luminal analysis
Rifaximin 200 mg
10 d
Stool and
luminal analysis
Rifaximin 200 mg
10 d
30 d
No Rifaximin
Stool and
luminal analysis
Recovery time
of flora
Stool analysis: bacterial quantitation by culture and qPCR (coliform and Staphylococcus spp.)
Luminal analysis: bacterial quantitation by qPCR in pre-specified segments of intestine
Susceptibility testing: to Rifampicin in Staphylococcus spp.

45. ‹#›
RESULTS
•Modest but significant reduction in
coliform counts in stool
•Recovery after 3 days
•No effect of Rifaximin on luminal
coliform counts
Coliform counts in stool
•After Rifaximin no colonies were
resistant and only one was
intermediate
•MIC for rifampicin was not different
before and after rifaximin
Staphylococcal resistance
“rifampin-resistant strains of human skin staphylococci
emerge after oral intake of rifaximin and can still be
found nine weeks after discontinuation of intake”
Valentin Jinfect 2011

46. ‹#›
RESULTS
•Rifaximin reduces
bacterial levels in
small bowel but
not in colon
•Durable effect on
total duodenal
bacterial counts

47. ‹#›
CONCLUSIONS
A 10-day course of rifaximin has a modest
but significant effect on stool coliforms
and Staphylococcal spp.
These counts recover within 3 days of
cessation of therapy.
The greatest effect of rifaximin appears to
be on duodenal bacteria with a milder
effect on colonic flora. This effect appears
to last for at least 30 days after
completion of the antibiotic.
Rifaximin gavage for 10 days reduces the total staphylococcal colony counts. Although Staphylococcus
spp. persist after high dose rifaximin, none of the staphylococcus species demonstrate resistance to
rifampicin. There were resistant colonies to rifampicin even before the administration of rifaximin. These
were not seen after rifaximin, suggesting they may have been reduced by rifaximin. Thus
rifaximin does not appear to select for rifampicin resistance in Staphylococci spp. after a 10-day course.
SIBO in IBS
FLORA
RESISTANCE

48. ‹#›

49. ‹#›
An Evidence-Based Position Statement on the Management of
Irritable Bowel Syndrome
The American College of Gastroenterology IBS Task Force.
Non-absorbable antibiotics (Rifaximin largely being the most studied one) has
been included in this position statement for the treatment of IBS and bloating with
a grade IB recommendation (strong recommendation, moderate quality evidence).
No other therapeutic option available on the market has received grade IA
recommendation.
Am J Gastroenterol 104S1, 2009

50. ‹#›
Page 5:
Effectiveness of antibiotics in the management of irritable bowel syndrome
A short- term course of a nonabsorbable antibiotic is more effective than placebo for global
improvement of IBS and for bloating (Grade IB). There are no data available to support the long-term
safety and effectiveness of nonabsorbable antibiotics for the management of IBS symptoms.
“…rifaximin consistently demonstrates improvement in global IBS symptoms and bloating in well-
designed trials. The majority of patients in rifaximin trials had IBS-D. Therefore, rifaximin is most likely to
be beneficial in IBS-D patients or IBS patients with bloating as their primary symptom. The most
appropriate dose of rifaximin for IBS is unclear. Based on currently available data, 400 mg three times a
day for 10 – 14 days is efficacious. IBS symptom relief appears to last for 10 – 12 weeks, but symptoms
may recur over three to nine months.”
Am J Gastroenterol 104S1, 2009
ACG GUIDELINES

51. ‹#›
Other recommendations
In patients with diarrhea, 5-hydroxytriptamine 3 antagonists such as alosetron are effective, based on
good-quality evidence. Because of the risk for ischemic colitis, however, patients should be carefully
selected.
In patients with constipation, 5-hydroxytriptamine 4 agonists such as tegaserod are modestly effective,
based on good-quality evidence. However, the possible risk for cardiovascular events linked to these
agents limits their usefulness.
In patients with any of the IBS subtypes, tricyclic antidepressants and selective serotonin reuptake
inhibitors have been shown to be effective in alleviating abdominal pain and global symptoms. The
quality of evidence supporting the usefulness of these drugs was graded as moderate because the trials
were generally of good quality, but the overall number of patients enrolled meant that additional
evidence could change the confidence in the estimate of effect. Safety and tolerability data for these
medications in patients with IBS are limited.
ACG GUIDELINES
Am J Gastroenterol 104S1, 2009

52. ‹#›
-Alteration of gut microbiota is on the basis of IBS pathogenesis
but it is not important to identify the bacteria responsible of
symptomatology
-Rifaximin is able to provide significant relief of IBS symptoms
(bloating, abdominal pain, loose or watery stools) with a safety
profile comparable to placebo
-The durable effect of Rifaximin suggests its action is directed on
the underlying cause of IBS that is linked to an alteration of
intestinal microbiota
TAKE HOME MESSAGE
THM