1. CLINICAL SIGNIFICANCE AND
PPI-RELATED SIBO:
CLINICAL SIGNIFICANCE AND
RISK FACTORS
Lucio LOMBARDO
Monica FOTI, Olga RUGGIA
Dept. Gastroenterology
Mauriziano Hospital, Turin
Italy
DDW- AGA 2009

2. Background
Antisecretory medications increase bacterial count in gastric (1) and in duodenal fluids (2, 3)
PPI use is associated with SIBO recurrence after eradication with antibiotics (4)
Presence of diarrhea in the elderely is positively associated with administration (among other drugs) of PPI (5)
1) Sanduleanu et al, Aliment Pharmacol Therap 2001;
2) Thorens et al, Gut, 1996;
3) Fried et al, Gut, 1994;
4) Lauritano et al, Am J Gastro, 2008;
5) Pilotto et al, Am J Gastro, 2008

3. To determine, in patients on long-term PPI treatment:
Aims of the study
To determine, in patients on long-term PPI treatment:
SIBO prevalence by glucose H2 breath test (HBT)
Risk factor for development of PPI-related SIBO
Clinical manifestations of PPI-related SIBO
Eradication of SIBO after Rifaximin

4. Evaluation of SIBO
Aspiration and culture of duodenal-jejunal fluid gold standard (1).
Hydrogen breath test:
indirect (metabolic) evidence of bacteria
Non Invasive
Repeatible
Sensible
Specific
It measures bacterial load It identifies bacterial species,
but
Cumbersome
Invasive
Low reproducibility
Low sensitivity
1) Lin, JAMA 2004

5. 200 patients on PPI for GERD treatment
Studied population
200 patients on PPI for GERD treatment
Eso 35%, Lan 30%, Ome 15%, Rabe 10%, Panto 10%,
PPI duration: medn 36 months (range: 2 months 7 years at standard dosage)
68% Hp-
Age, meanS.D.: 39 ± 18; M/F:120/80
200 IBS (Rome III criteria)
Subtype: Diarrhea 40%, Constipation 40%, Mixed 20%)
Age, meanS.D.: 37±19, M/F:102/98
50 Healthy controls
Age, meanS.D.: 35±16, M/F:29/21

6. Main inclusion Criteria
Patients:
Age:
On PPI > 2 months
IBS Controls:
Age : 18-75
Rome III criteria
No PPI for at least 3 years
Healthy Controls:
Age: 18-75
N0 PPI for at last 10 years

7. Main exclusion Criteria
History of neoplasia, malabsorptions, GI surgery, metabolic or hormonal disease
Use of antibiotics in the last 6 months
Use of eukinetic laxatives, history of colonscopy or X-ray barium enema in the last month

8. Instrument: E.C.60 Gastrolyzer 50 g Glucose in 250mL
Glucose H2Breath Test
Instrument: E.C.60 Gastrolyzer
50 g Glucose in 250mL
Breath sampling: every 15’ until 120’
Accuracy: ± 2% of Reading
Sensor Sensitivity 1 ppm
Positivity criteria: increase >10 ppm in the first 120’
Gasbarrini Aliment Pharmacol Therap, 2009

9. Evaluation of 5 symptoms by a 3-point scale (0-3)
Symptom Index (S.I.)
Evaluation of 5 symptoms by a 3-point scale (0-3)
Pain Severity
Pain Duration
Pain Frequency
Bloating
Constipation / Diarrhea severity
Symptom index calculating the sum of the above symptoms score
Mild / no symptoms:
Moderate:
Severe:

10. SIBO treatment
SIBO-positive were treated with the non-absorbable antibiotic Rifaximin 400 mg t.i.d. (1,200 mg) for 2 weeks. PPI treatment was continued
Assessment of SIBO eradication by GHBT 2 months after completion of treatment

11. Statistics
SPSS software version 12 for W
Mann-Whitney test
X2 test with Yate’s correction

12. Glucose-HBT Positivity
PPI vs IBS : p< OR 3.14
PPI vs HC: p < OR 16.0

13. Age Distribution in PPI and IBS G-HBT positive patients

14. Prevalence of SIBO / Duration of PPI treatment
2-12 Mo vs >13 Mo : p < 0.001, OR: 11

15. SIBO Symptom Severity / Duration of PPI treatment

16. Type of symptoms in SIBO patients

17. SIBO eradication rate following Rifaximin 1,200 mg/day for 14 days
P : NS

18. SIBO eradication according to PPI treatment duration
P : NS

19. Safety
Tolerability of Rifaximin was excellent with only a 2% of minor side-effects (headache, nausea of mild grade, with prompt remission after cessation of treatment).

20. Conclusions 1
PPI – Related SIBO
SIBO is more frequent in patients on long-term PPI treatment than in IBS patients and healthy controls
Prevalence of PPI-related SIBO and severity of symptoms increase with duration of PPI treatment
Bloating is more frequent in PPI-related SIBO than in IBS-related SIBO

21. ERADICATION OF PPI – Related SIBO
Conclusions 2
ERADICATION OF PPI – Related SIBO
Satisfactory (87-91%)
More Successful in patients on PPI < 12 Months
Tolerability: excellent
Recurrence in PPI population to be evaluated

22. pH 4: Most Bacteria killed in 30’ (Gut 1972,13:251)
CONSIDERATIONS
pH 4: Most Bacteria killed in 30’
(Gut 1972,13:251)
? PPI –Tx Tailoring with 2 aims:
1)tissue repair maintenance
2) gastric pH “physiological respect”:
?PPI à la démande
?Periodical
?Less aggressive

23. Limitations of the study
Observational transversal
Open label study design
Single PPI differentiation
Hp status on SIBO

24. without influencing comorbidities IBS pts “free” from PPI use
MAJOR VALUES
Long-term PPI Tx in Pts
without influencing comorbidities
IBS pts “free” from PPI use
HC “free” from PPI use
Satisfactory Eradication with Rifaximin

25. THANK YOU !