S1014 The Modest Differential Effects of Rifaximin Alone vs Rifaximin Plus Lactulose on Intestinal Microbial Diversity and Composition in Patients With Cirrhosis

Abstract

INTRODUCTION: Rifaximin, a nonsystemic antibiotic, is indicated in the United States for reducing the risk of overt hepatic encephalopathy (OHE) recurrence in adults and may be used alone or in combination with lactulose. This analysis employed genomic characterization to assess the impact of daily rifaximin alone or rifaximin + lactulose treatment on stool microbiota in patients with a history of OHE. METHODS: In a randomized, open-label trial, patients aged ≥18 y with cirrhosis and history of ≥1 OHE episode during the prior 6 months, currently in HE remission (Conn score ≤1), received rifaximin 550 mg twice daily (BID) or rifaximin 550 mg BID + lactulose (titrated to 2–3 soft stools/d) for 6 months. Stool samples were collected at screening (baseline) and month 6/end of treatment (EOT). Patients were randomly selected for the stool microbiota sequencing analysis substudy. Genomic characterization of microbiota was achieved using 16S rRNA bacterial deep gene sequencing. Metrics included stool microbiota richness (number of bacterial species in a sample, adjusted for different numbers of sequences observed from each sample), evenness (relative abundance of different species [range, 0–1; 1 = complete evenness]), and Shannon diversity index (richness and evenness [overall community complexity]). RESULTS: Sixty-six adults (mean age, 56.0 y; 68.2% male; mean body mass index, 31.7 kg/m2) were randomly selected for stool microbiota analysis (rifaximin alone [n = 34]; rifaximin + lactulose [n = 32]; demographics evenly matched). At baseline, measures of richness and evenness of stool microbiota and Shannon diversity index were similar for rifaximin alone and rifaximin + lactulose groups (Table 1). Stool microbiota richness did not significantly change from baseline to EOT in either group; no significant difference was observed between groups. Significant decreases from baseline to EOT were seen in evenness of stool microbiota and Shannon diversity index in the rifaximin alone group (P < 0.005 for both measures); greater reductions in these parameters were observed in the rifaximin alone group versus the rifaximin + lactulose group (P < 0.05 for both measures). CONCLUSION: Modest effects on stool microbiota diversity and evenness, with no effects on the absolute number of species, were observed in the rifaximin alone group. Concomitant lactulose may offset these effects, but further research is needed. Overall, data support that overall effects to stool microbiota during rifaximin treatment are modest in scope.Table 1