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

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

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

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

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

Main inclusion Criteria Patients: Age: 18- 75 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

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

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

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: 0-5 Moderate: 6-10 Severe: 11-15

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

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

Glucose-HBT Positivity PPI vs IBS : p< 0.001 OR 3.14 PPI vs HC: p <0.001 OR 16.0

Age Distribution in PPI and IBS G-HBT positive patients

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

SIBO Symptom Severity / Duration of PPI treatment

Type of symptoms in SIBO patients

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

SIBO eradication according to PPI treatment duration P : NS

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).

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

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

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

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

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

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