S1013 Lack of Colonic Microbial Cross-Resistance to Other Antibiotics in Patients Treated With Rifaximin Alone vs Rifaximin Plus Lactulose for Reducing the Risk of Overt Hepatic Encephalopathy (OHE) Recurrence

Abstract

INTRODUCTION: Rifaximin is a nonsystemic antibiotic indicated for reducing the risk of OHE recurrence in adults. The risk of bacterial antibiotic resistance to rifaximin and cross-resistance to other antibiotics is thought to be low, possibly because of minimal systemic absorption. Data are limited on the potential impact of concomitant lactulose. This phase 4 substudy assessed rifaximin ± lactulose on antibiotic susceptibility of fecal bacteria in patients with cirrhosis and a history of overt HE. METHODS: Adults with cirrhosis and history of ≥1 OHE episode during previous 6 months, currently in OHE remission (Conn score ≤1) were randomized to receive open-label 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 fecal microbiota antibiotic susceptibility substudy. Bacteria were cultured using standard techniques; susceptibility to several antibiotics, depending on bacterium, was tested by broth or agar dilution methods; and minimum inhibitory concentrations (MIC) were determined. Control strains were included per lab SOP practices. RESULTS: Sixty-four patients (mean age, 55.8 y; 64.1% male) were included (rifaximin: n = 31; rifaximin + lactulose: n = 33). Overall, 376 bacterial isolates were identified: Enterobacteriaceae (36.2%), Enterococcaceae (27.7%), Bacteroidaceae (25.5%) families, Staphylococcaceae (7.2%), and Clostridiaceae (3.5%). Patients in each group had a similar distribution of bacterial families and species at baseline and EOT. Cross resistance to other antibiotics rarely developed (Table 1). CONCLUSION: Rifaximin ± lactulose for up to 6 months did not lead to clinically relevant changes to fecal microbial antibiotic susceptibility profiles. There was no indication of clinically relevant antibiotic resistance with the addition of lactulose to rifaximin therapy for the prevention of OHE recurrence. These data support the clinical safety profile of rifaximin + lactulose in adults with cirrhosis.Table 1