In vitro activity of rifaximin against isolates from patients with small intestinal bacterial overgrowth

Rifaximin, a non-absorbable rifamycin derivative, has published clinical efficacy in the alleviation of symptoms in patients with irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) is associated with the pathogenesis of IBS. This study describes for the first time the antimicrobial effect of rifaximin against SIBO micro-organisms from humans. Fluid was aspirated from the third part of the duodenum from 567 consecutive patients; quantitative cultures diagnosed SIBO in 117 patients (20.6%). A total of 170 aerobic micro-organisms were isolated and the in vitro efficacy of rifaximin was studied by (i) minimum inhibitory concentration (MIC) testing by a microdilution technique and (ii) time-kill assays using bile to simulate the small intestinal environment. At a breakpoint of 32 μg/mL, rifaximin inhibited in vitro 85.4% of Escherichia coli, 43.6% of Klebsiella spp., 34.8% of Enterobacter spp., 54.5% of other Enterobacteriaceae spp., 82.6% of non-Enterobacteriaceae Gram-negative spp., 100% of Enterococcus faecalis, 100% of Enterococcus faecium and 100% of Staphylococcus aureus. For the time-kill assays, 11 E. coli, 15 non-E. coli Gram-negative enterobacteria and three E. faecalis isolates were studied. Rifaximin produced a >3 log10 decrease in the starting inoculum against most of the tested isolates at 500 μg/mL after 24h of growth. The results indicate that rifaximin has a potent effect on specific small bowel flora associated with SIBO. This conclusion should be regarded in light of the considerable time-kill effect at concentrations lower than those achieved in the bowel lumen after administration of conventional doses in humans.