Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea

Rezaie A1, Heimanson Z2, McCallum R3, Pimentel M4. Am J Gastroenterol. 2019 Dec;114(12):1886-1893. doi: 10.14309/ajg.0000000000000444.


Author information

GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Salix Pharmaceuticals, Bridgewater, New Jersey, USA.

Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA.

Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USA.


OBJECTIVES: The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined.

METHODS: Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was conducted before (day 1) and after (day 14) therapy (breath samples obtained every 15 minutes; up to 240 minutes). Patient response (decrease from baseline of ≥30% in abdominal pain and ≥50% decrease in frequency of mushy/watery stool), symptom improvement, and the relationship of clinical outcomes to LBT results were assessed.

RESULTS: A total of 93 patients were included; 62 (66.7%) had positive baseline LBT results. Overall, 48.4% (45/93) of patients responded to rifaximin; of these, 59.7% (37/62) had a positive baseline LBT vs 25.8% (8/31) with a negative LBT (P = 0.002; odds ratio 4.3, 95% confidence interval, 1.5-12.7). Patients with a positive baseline LBT result experienced significantly greater improvement from baseline in 6 of 7 individual IBS symptoms. LBT results after rifaximin therapy did not correlate with clinical response in the 86 patients with evaluable breath tests (P = 0.21); however, patients whose LBT results normalized after rifaximin had the highest response rate of 76.5% (13/17).

DISCUSSION: A positive baseline LBT result predicted a higher likelihood of response to rifaximin in IBS-D, suggesting a gut microbiome modulatory mechanism of action for rifaximin.

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